全外显子组测序探寻中国汉族人群先天性脊柱侧凸致病基因的研究
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摘要
研究背景：
先天性脊柱侧凸(Congenital scoliosis,CS)是由胚胎期椎体发育异常导致的脊柱侧方弯曲≥10°。CS具有进展快、畸形重、并发症多等特点,严重时可致患者瘫痪,是造成青少年残疾的主要疾病之一,给家庭和社会带来极大负担。
脊椎动物的脊柱是由体前中胚层周期性形成的体节发育而来,这一过程叫做体节形成(somitogenesis),体节形成异常即可导致先天性椎体畸形。体节形成是由WNT、NOTCH和FGF三个通路及其中的基因相互作用、共同调节来完成的。由于其确切病因不明,目前尚无有效的预测手段,治疗仍以支具或手术治疗来缓解病情发展为主,因此探寻其发病原因,对于从病因学领域控制发病率、早期诊断和早期干预这种严重致残性脊柱畸形疾病、缓解家庭和社会负担具有重要意义。CS可由基因异常或环境因素变化导致,随着越来越多的遗传学病因报道,遗传因素在CS发病中起到的作用逐渐被人们重视。CS是一种复杂、多基因、多遗传模式疾病。目前国际上对于CS的遗传学病因研究少有大样本的遗传学研究报道,难以获得临床表型一致的大样本病例、基于人数共线性模型的研究策略以及CS的遗传异质性等是限制开展大规模研究的主要因素。
随着测序技术的不断进步,高通量测序成本逐渐下降,全外显子组测序(Whole exome sequence, WES)已成为最有效的进行疾病定位研究的手段。WES是一种高效、快速和高性价比的研究方法,该技术被《Science》杂志评为2010年十大科学突破之一。到目前为止,已有百余篇报道应用外显子组测序成功定位了大量疾病的致病突变。WES的出现给CS遗传学研究提供了方法学的革新,为从组学水平探究CS遗传致病因素提供了可能,人们能够从以往“被动”的以“人鼠共线性”为基础的候选基因研究策略,上升为“主动”的从“全外显子组水平”寻找CS的致病性突变。
研究目的：
本研究以中国汉族人群CS患者为研究对象,拟在全外显子组水平寻找与CS发病相关的基因突变。
研究内容：
选取4例散发(编号分别为CS012/CS039/CS070/CS108)及1例核心家系trio (CS051/CS052/CS053)的中国汉族人群CS患者(临床分型为Ⅲ型, ICVAS分型为M-SDV-U),完整采集数据资料。排除环境因素影响后,采集外周静脉血4-6m1,提取全基因组DNA。对上述样本进行WES,所得数据采用严格的质量控制,数据分析时考虑多种显性遗传及隐性遗传模型的可能,并在以往研究的基础上,对数据进行深入挖掘,以探索CS可能的致病突变。
研究结果：
1、在隐性遗传模型下,没有发现2个以上患者共有的杂合或纯合突变。
2、在显性新发突变遗传模型下,在CS051患者中得到了1个可以导致编码氨基酸改变的新发突变(FAM179B,14_45475484_A/G),但功能上没有明确的意义。
3、在不完全外显的显性遗传模型下,分别得到1个基因(FANCA)的两个非同义突变(CS05116_89833556_A/G和CS10816_89842161_T/A)为2个患者共有,无3个或以上患者共有的突变。
4、经过基于先验的深入挖掘,分别得到ZIC3(CS070X_136651147_A/T、CS108X_136648948_C/T)和TBX6(CS07016_30100451_G/A)2个基因的感兴趣突变。
研究结论：
1、采用“核心家系结合散发病例、在多模型下探寻全外显子组水平致病突变"的策略,是CS遗传学研究较为可行的思路。
2、FANCA基因突变(16_89833556_A/G和16_89842161-T/A)可能与CS发病密切相关,其遗传模式可能为不完全外显的显性遗传。
3、ZIC3基因突变(X_136651147_A/T和X_136648948_C/T)可能导致CS的发生,其可能与CS患者伴有神经管发育异常及心脏发育障碍的表型有关。
4、TBX6基因突变(16_30100451_G/A)可能是CS的致病因素之一,TBX6基因异常可能与CS患者伴有肋骨畸形的表型有关。
Background:
Congenital Scoliosis (CS) is a spinal deformity with a spinal coronary curvature of10°or greater caused by abnormal vertebrate development during embryo. CS is charatered by rapid development, severe deformity and multiple complications. It is one of the most causes of adolescent disability and brings high burden to the family and the society.
The spine of the vertebrate is developed from the presomitc mesoderm (PSM) from which somite is periodically developed, this process is called somitogenesis. Abnormal somitogenesis is the reason of congenital vertebrate deformity. Somitogenesis is regulated by the mutual cooperation of WNT, NOTCH and FGF signaling pathway and their taget genes. However, the definite etiology of CS is obscure and there is still no effective method for its early prediction. Clinially, the treatment of CS is mainly focused on bracement and operation in order to avoid the rapid progress of the disease. Therefore, it is important to find the etiology and to reduce the occurrence of this high pathogenic spinal deformity.
The abnormal of genes and changes of environmental factors in embryo or during labor are the main casue of CS. With more and more genetic etiology were reported, the genetic influence of CS is gradually remarked. CS is a complicated disease with multiple genes and multi genetic models related. Little larege sample of genetics research of CS was reported because it is difficult to collect large scale of patients with the same phenotype as patients are usually infertile, furthermore, the strategy of analysis based on the mouse-human synteny restricts the profound and creative study as the real mechanism of molecular biological etiology of CS is unknow either.
With the rapid advancement of the sequencing technique, the coast of sequencing is reducing correspondingly. Up to now, whole exome sequencing (WES) has been the most effective method to locate the genetic cause of diseases. WES is a high-performance method in detecting mutations in exome wide and according to the journal of "Science", WES was chosen as one of the top ten breakthroughs of science in2010. There are hundreds of publications reporting using WES to find the genetics etiology of certain disease. As the importance of WES is realized by more and more researchers and the further decline of the cost of WES, it will be used in more cases especially those complicated ones and more important genetic foundamental knowledge of disease wll be provided. The apperance of WES brings evolution in methodology of genetic research of CS, and it is possible for us to find the pathogenic mutation in the level of exome wide.
Objects:
To investigate the genetic mutation of CS in whole exome level.
Methods:
We collected four sporadic cases (CS012/CS039/CS070/CS108) and one trio of CS (CS051/CS052/CS053) in Chinese Han population, the classification was type III clinically and M-SDV-U according to ICVAS. Genomic DNA was draw from the whole peripheral blood. We used whole exome sequencing and construct different models in statistical analysis to identify genetic mutations in these cases.
Results:
1. No homozygous of compound heterozygou mutation were shared by two or more patients in recessive model.
2. One non-synonymous mutation of FAM179B (CS05114_45475484_A/G) was identified in dominant de novo mutation model, but functionally inexplainable.
3. Two non-synonymous mutations of FANCA (CS05116_89833556_A/G and CS1081689842161_T/A) were identified in two cases. No exome mutation was found in three or more cases.
4. After knowledge-based data mining, two candidate mutations, ZIC3(CS070X_136651147_A/T、CS108X_136648948_C/T) and TBX6(CS01016_30100451_G/A), were identified.
Conclusions:
1. The strategy of "sporadic cases combined with trio in identifying exome level mutatoins of CS in mutiple models" is a feasible approcah for genetic research of CS.
2. The mutation of FANCA (16_89833556_A/G and16_89842161_T/A) may be closely related to CS with the model of incomplete penetrance.
3. The mutation of ZIC3(X_136651147_A/T and X_136648948_C/T) may be the cause of CS especially those associated with neural tube defects and congenital heart malformations.
4. The mutation of TBX6(16_30100451_G/A) may be the cause of CS especially those associated with abnormal ribs.
先天性脊柱侧凸(Congenital scoliosis,CS)是由胚胎期椎体发育异常导致的脊柱侧方弯曲≥10°。CS具有进展快、畸形重、并发症多等特点,严重时可致患者瘫痪,是造成青少年残疾的主要疾病之一,给家庭和社会带来极大负担。
脊椎动物的脊柱是由体前中胚层周期性形成的体节发育而来,这一过程叫做体节形成(somitogenesis),体节形成异常即可导致先天性椎体畸形。体节形成是由WNT、NOTCH和FGF三个通路及其中的基因相互作用、共同调节来完成的。由于其确切病因不明,目前尚无有效的预测手段,治疗仍以支具或手术治疗来缓解病情发展为主,因此探寻其发病原因,对于从病因学领域控制发病率、早期诊断和早期干预这种严重致残性脊柱畸形疾病、缓解家庭和社会负担具有重要意义。CS可由基因异常或环境因素变化导致,随着越来越多的遗传学病因报道,遗传因素在CS发病中起到的作用逐渐被人们重视。CS是一种复杂、多基因、多遗传模式疾病。目前国际上对于CS的遗传学病因研究少有大样本的遗传学研究报道,难以获得临床表型一致的大样本病例、基于人数共线性模型的研究策略以及CS的遗传异质性等是限制开展大规模研究的主要因素。
随着测序技术的不断进步,高通量测序成本逐渐下降,全外显子组测序(Whole exome sequence, WES)已成为最有效的进行疾病定位研究的手段。WES是一种高效、快速和高性价比的研究方法,该技术被《Science》杂志评为2010年十大科学突破之一。到目前为止,已有百余篇报道应用外显子组测序成功定位了大量疾病的致病突变。WES的出现给CS遗传学研究提供了方法学的革新,为从组学水平探究CS遗传致病因素提供了可能,人们能够从以往“被动”的以“人鼠共线性”为基础的候选基因研究策略,上升为“主动”的从“全外显子组水平”寻找CS的致病性突变。
研究目的：
本研究以中国汉族人群CS患者为研究对象,拟在全外显子组水平寻找与CS发病相关的基因突变。
研究内容：
选取4例散发(编号分别为CS012/CS039/CS070/CS108)及1例核心家系trio (CS051/CS052/CS053)的中国汉族人群CS患者(临床分型为Ⅲ型, ICVAS分型为M-SDV-U),完整采集数据资料。排除环境因素影响后,采集外周静脉血4-6m1,提取全基因组DNA。对上述样本进行WES,所得数据采用严格的质量控制,数据分析时考虑多种显性遗传及隐性遗传模型的可能,并在以往研究的基础上,对数据进行深入挖掘,以探索CS可能的致病突变。
研究结果：
1、在隐性遗传模型下,没有发现2个以上患者共有的杂合或纯合突变。
2、在显性新发突变遗传模型下,在CS051患者中得到了1个可以导致编码氨基酸改变的新发突变(FAM179B,14_45475484_A/G),但功能上没有明确的意义。
3、在不完全外显的显性遗传模型下,分别得到1个基因(FANCA)的两个非同义突变(CS05116_89833556_A/G和CS10816_89842161_T/A)为2个患者共有,无3个或以上患者共有的突变。
4、经过基于先验的深入挖掘,分别得到ZIC3(CS070X_136651147_A/T、CS108X_136648948_C/T)和TBX6(CS07016_30100451_G/A)2个基因的感兴趣突变。
研究结论：
1、采用“核心家系结合散发病例、在多模型下探寻全外显子组水平致病突变"的策略,是CS遗传学研究较为可行的思路。
2、FANCA基因突变(16_89833556_A/G和16_89842161-T/A)可能与CS发病密切相关,其遗传模式可能为不完全外显的显性遗传。
3、ZIC3基因突变(X_136651147_A/T和X_136648948_C/T)可能导致CS的发生,其可能与CS患者伴有神经管发育异常及心脏发育障碍的表型有关。
4、TBX6基因突变(16_30100451_G/A)可能是CS的致病因素之一,TBX6基因异常可能与CS患者伴有肋骨畸形的表型有关。
Background:
Congenital Scoliosis (CS) is a spinal deformity with a spinal coronary curvature of10°or greater caused by abnormal vertebrate development during embryo. CS is charatered by rapid development, severe deformity and multiple complications. It is one of the most causes of adolescent disability and brings high burden to the family and the society.
The spine of the vertebrate is developed from the presomitc mesoderm (PSM) from which somite is periodically developed, this process is called somitogenesis. Abnormal somitogenesis is the reason of congenital vertebrate deformity. Somitogenesis is regulated by the mutual cooperation of WNT, NOTCH and FGF signaling pathway and their taget genes. However, the definite etiology of CS is obscure and there is still no effective method for its early prediction. Clinially, the treatment of CS is mainly focused on bracement and operation in order to avoid the rapid progress of the disease. Therefore, it is important to find the etiology and to reduce the occurrence of this high pathogenic spinal deformity.
The abnormal of genes and changes of environmental factors in embryo or during labor are the main casue of CS. With more and more genetic etiology were reported, the genetic influence of CS is gradually remarked. CS is a complicated disease with multiple genes and multi genetic models related. Little larege sample of genetics research of CS was reported because it is difficult to collect large scale of patients with the same phenotype as patients are usually infertile, furthermore, the strategy of analysis based on the mouse-human synteny restricts the profound and creative study as the real mechanism of molecular biological etiology of CS is unknow either.
With the rapid advancement of the sequencing technique, the coast of sequencing is reducing correspondingly. Up to now, whole exome sequencing (WES) has been the most effective method to locate the genetic cause of diseases. WES is a high-performance method in detecting mutations in exome wide and according to the journal of "Science", WES was chosen as one of the top ten breakthroughs of science in2010. There are hundreds of publications reporting using WES to find the genetics etiology of certain disease. As the importance of WES is realized by more and more researchers and the further decline of the cost of WES, it will be used in more cases especially those complicated ones and more important genetic foundamental knowledge of disease wll be provided. The apperance of WES brings evolution in methodology of genetic research of CS, and it is possible for us to find the pathogenic mutation in the level of exome wide.
Objects:
To investigate the genetic mutation of CS in whole exome level.
Methods:
We collected four sporadic cases (CS012/CS039/CS070/CS108) and one trio of CS (CS051/CS052/CS053) in Chinese Han population, the classification was type III clinically and M-SDV-U according to ICVAS. Genomic DNA was draw from the whole peripheral blood. We used whole exome sequencing and construct different models in statistical analysis to identify genetic mutations in these cases.
Results:
1. No homozygous of compound heterozygou mutation were shared by two or more patients in recessive model.
2. One non-synonymous mutation of FAM179B (CS05114_45475484_A/G) was identified in dominant de novo mutation model, but functionally inexplainable.
3. Two non-synonymous mutations of FANCA (CS05116_89833556_A/G and CS1081689842161_T/A) were identified in two cases. No exome mutation was found in three or more cases.
4. After knowledge-based data mining, two candidate mutations, ZIC3(CS070X_136651147_A/T、CS108X_136648948_C/T) and TBX6(CS01016_30100451_G/A), were identified.
Conclusions:
1. The strategy of "sporadic cases combined with trio in identifying exome level mutatoins of CS in mutiple models" is a feasible approcah for genetic research of CS.
2. The mutation of FANCA (16_89833556_A/G and16_89842161_T/A) may be closely related to CS with the model of incomplete penetrance.
3. The mutation of ZIC3(X_136651147_A/T and X_136648948_C/T) may be the cause of CS especially those associated with neural tube defects and congenital heart malformations.
4. The mutation of TBX6(16_30100451_G/A) may be the cause of CS especially those associated with abnormal ribs.
引文
[1]M. J. McMaster,K. Ohtsuka. The natural history of congenital scoliosis. A study of two hundred and fifty-one patients[J]. J Bone Joint Surg Am.1982.64 (8):1128-1147
[2]AR Jr SHANDS,H. B. EISBERG. The incidence of scoliosis in the state of Delaware; a study of 50,000 minifilms of the chest made during a survey for tuberculosis[J]. J Bone Joint Surg Am.1955.37-A (6): 1243-1249
[3]M. J. McMaster,H. Singh. Natural history of congenital kyphosis and kyphoscoliosis. A study of one hundred and twelve patients[J]. J Bone Joint Surg Am.1999.81 (10):1367-1383
[4]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[5]D. Jaskwhich,R. M. Ali,T. C. Patelet al. Congenital scoliosis[J]. CURRENT OPINION IN PEDIATRICS.2000.12 (1):61-66
[6]D. Hedequist,J. Emans. Congenital scoliosis:a review and update[J]. J Pediatr Orthop.2007.27 (1) 106-116
[7]A. Offiah,B. Alman,A. S. Cornieret al. Pilot assessment of a radiologic classification system for segmentation defects of the vertebrae[J]. Am J Med Genet A.2010.152A (6):1357-1371
[8]M. L. Dequeant,O. Pourquie. Segmental patterning of the vertebrate embryonic axis[J]. NATURE REVIEWS GENETICS.2008.9 (5):370-382
[9]N. Cambray,V. Wilson. Two distinct sources for a population of maturing axial progenitors[J]. Development.2007.134 (15):2829-2840
[10]E. Tzouanacou,A. Wegener.F. J. Wymeerschet al. Redefining the progression of lineage segregations during mammalian embryogenesis by clonal analysis[J]. Dev Cell.2009.17 (3):365-376
[11]A. Aulehla,W. Wiegraebe,V. Baubetet al. A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation[J]. Nat Cell Biol.2008.10 (2):186-193
[12]I. Palmeirim,S. Rodrigues,J. K. Daleet al. Development on time[J]. Adv Exp Med Biol.2008.641: 62-71
[13]C. Schroter,L. Herrgen,A. Cardonaet al. Dynamics of zebrafish somitogenesis[J]. Dev Dyn.2008.237 (3):545-553
[14]S. A. Holley. The genetics and embryology of zebrafish metamerism[J]. Dev Dyn.2007.236 (6) 1422-1449
[15]I. Bothe,M. U. Ahmed,F. L. Winterbottomet al. Extrinsic versus intrinsic cues in avian paraxial mesoderm patterning and differentiation[J]. Dev Dyn.2007.236 (9):2397-2409
[16]O. Pourquie. Vertebrate segmentation:from cyclic gene networks to scoliosis[J]. Cell.2011.145 (5) 650-663
[17]P. C. Rida,N. Le Minh,Y. J. Jiang. A Notch feeling of somite segmentation and beyond[J]. Dev Biol. 2004.265 (1):2-22
[18]Z. Ferjentsik,S. Hayashi,J. K. Daleet al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites[J]. PLoS Genet.2009.5(9):e1000662
[19]S. Gibb,M. Maroto,J. K. Dale. The segmentation clock mechanism moves up a notch[J]. Trends Cell Biol.2010.20 (10):593-600
[20]K. Bruckner.L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[21]D. J. Moloney,V. M. Panin,S. H. Johnstonet al. Fringe is a glycosyltransferase that modifies Notch[J]. Nature.2000.406 (6794):369-375
[22]G. Weinmaster,C. Kintner. Modulation of Notch signaling during somitogenesis[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY.2003.19:367-395
[23]R. T. Moon,A. D. Kohn,G. V. De Ferrariet al. WNT and beta-catenin signalling:diseases and therapies[J]. Nat Rev Genet.2004.5 (9):691-701
[24]H. Huang,X. He. Wnt/beta-catenin signaling:new (and old) players and new insights[J]. Curr Opin Cell Biol.2008.20 (2):119-125
[25]L. Ciani,P. C. Salinas. WNTs in the vertebrate nervous system:from patterning to neuronal connectivity [J]. Nat Rev Neurosci.2005.6(5):351-362
[26]W. Lu,V. Yamamoto,B.Ortegaet al. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth[J]. Cell.2004.119 (1):97-108
[27]Y. Zou. Wnt signaling in axon guidance[J]. Trends Neurosci.2004.27 (9):528-532
[28]M. Kuhl,L.C. Sheldahl,C. C. Malbonet al. Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus[J]. J Biol Chem. 2000.275 (17):12701-12711
[29]A. D. Kohn,R. T. Moon. Wnt and calcium signaling:beta-catenin-independent pathways[J]. Cell Calcium.2005.38 (3-4):439-446
[30]M. V. Semenov,R. Habas,B. T. Macdonaldet al. SnapShot:Noncanonical Wnt Signaling Pathways[J]. Cell.2007.131 (7):1378
[31]H. Takahashi,F. C. Liu. Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors[J]. Birth Defects Res C Embryo Today.2006.78 (3):256-266
[32]C. H. Kim,T. Oda,M. Itohet al. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation[J]. Nature.2000.407 (6806):913-916
[33]H. Popperl,C. Schmidt,V. Wilsonet al. Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm[J]. Development.1997.124 (15): 2997-3005
[34]N. S. Hamblet,N. Lijam,P. Ruiz-Lozanoet al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure[J]. Development. 2002.129 (24):5827-5838
[35]L. Zeng,F. Fagotto,T. Zhanget al. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation[J]. Cell.1997.90 (1):181-192
[36]M. Carter,X. Chen,B.Slowinskaet al. Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6[J]. Proc Natl Acad Sci U S A. 2005.102 (36):12843-12848
[37]C. Kokubu,U. Heinzmann,T. Kokubuet al. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis[J]. Development.2004.131 (21):5469-5480
[38]M. L. Dequeant,E.Glynn,K. Gaudenzet al. A complex oscillating network of signaling genes underlies the mouse segmentation clock[J]. Science.2006.314 (5805):1595-1598
[39]A. Kawamura.S. Koshida,H.Hijikataet al. Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites[J]. Genes Dev.2005.19 (10) 1156-1161
[40]P. H. Crossley,S. Martinez,G. R. Martin. Midbrain development induced by FGF8 in the chick embryo[J]. Nature.1996.380 (6569):66-68
[41]H. Shamim,R. Mahmood,C. Loganet al. Sequential roles for Fgf4, Enl and Fgf8 in specification and regionalisation of the midbrain[J]. Development.1999.126 (5):945-959
[42]T. Fukuchi-Shimogori,E. A. Grove. Neocortex patterning by the secreted signaling molecule FGF8[J]. Science.2001.294 (5544):1071-1074
[43]A. Aulehla,C. Wehrle,B. Brand-Saberiet al. Wnt3A plays a major role in the segmentation clock controlling somitogenesis[J]. DEVELOPMENTAL CELL.2003.4 (3):395-406
[44]I. Palmeirim,D. Henrique,D. Ish-Horowiczet al. Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis[J]. Cell.1997.91 (5):639-648
[45]P. C. Rida,N. Le Minh,Y. J. Jiang. A Notch feeling of somite segmentation and beyond[J]. Dev Biol. 2004.265 (1):2-22
[46]A. Aulehla,C. Wehrle,B.Brand-Saberiet al. Wnt3a plays a major role in the segmentation clock controlling somitogenesis[J]. Dev Cell.2003.4 (3):395-406
[47]M. Hofmann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[48]M. Hofinann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dlll expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[49]M. Hofmann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dlll expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[50]S. Gibb,A.Zagorska,K. Meltonet al. Interfering with Wnt signalling alters the periodicity of the segmentation clock[J]. Dev Biol.2009.330 (1):21-31
[51]M. B. Wahl,C. Deng,M. Lewandoskiet al. FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis[J]. Development. 2007.134 (22):4033-4041
[52]J. Dubrulle,M. J. McGrew,O. Pourquie. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation[J]. Cell.2001.106 (2):219-232
[53]A. Sawada,A. Fritz,Y. J. Jianget al. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites[J]. Development.2000.127 (8):1691-1702
[54]Y. Niwa,H. Shimojo,A. Isomuraet al. Different types of oscillations in Notch and Fgf signaling regulate the spatiotemporal periodicity of somitogenesis[J]. Genes Dev.2011.25 (11):1115-1120
[55]WC Jr Dunty,K. K. Biris,R. B. Chalamalasettyet al. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation[J]. Development.2008.135 (1):85-94
[56]J. K. Dale,P. Malapert,J. Chalet al. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis[J]. Dev Cell.2006.10(3): 355-366
[57]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cysticafJ]. J Med Genet.1975.12 (3):280-288
[58]G. H. Shahcheraghi,M. H. Hobbi. Patterns and progression in congenital scoliosis[J]. J Pediatr Orthop. 1999.19 (6):766-775
[59]J. M. Connor,A.N. Conner,R. A. Connoret al. Genetic aspects of early childhood scoliosis[J]. Am J Med Genet.1987.27 (2):419-424
[60]S. B. Purkiss,B. Driscoll,W. G. Coleet al. Idiopathic scoliosis in families of children with congenital scoliosis[J]. Clin Orthop Relat Res.2002 (401):27-31
[61]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[62]M. L. Martinez-Frias,E. Bermejo.L.Paisanet al. Severe spondylocostal dysostosis associated with other congenital anomalies:a clinical/epidemiologic analysis and description of ten cases from the Spanish registry[J]. Am J Med Genet.1994.51 (3):203-212
[63]D. B. Sparrow.G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[64]D. B. Sparrow,E. Guillen-Navarro,D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[65]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[66]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[67]P. Lorenz,E. Rupprecht. Spondylocostal dysostosis:dominant type[J]. Am J Med Genet.1990.35(2): 219-221
[68]Y. Floman. "Mirror image" congenital scoliosis in siblings[J]. J Spinal Disord.1991.4 (3):366-368
[69]N. Ghebranious,C. L. Raggio,R. D. Blanket al. Lack of evidence of WNT3A as a candidate gene for congenital vertebral malformations[J]. Scoliosis.2007.2:13
[70]M. K. Maisenbacher,J. S. Han,M. L. O'Brienet al. Molecular analysis of congenital scoliosis:a candidate gene approach[J]. Hum Genet.2005.116 (5):416-419
[71]P. F. Giampietro,S. L. Dunwoodie,K. Kusumiet al. Progress in the Understanding of the Genetic Etiology of Vertebral Segmentation Disorders in Humans G-2911-2010[M]. OXFORD,:BLACKWELL PUBLISHING,2009:38-67
[72]Q. Fei,Z. Wu,H. Wanget al. The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population[J]. Spine (Phila Pa 1976).2010.35 (9):983-988
[73]费琦,吴志宏,王以朋等LMX1A基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联[J].中国组织工程研究与临床康复,2011,15(35)：6632-6638.
[74]原所茂,吴志宏,魏斌等.HES7基因多态性与先天性脊柱侧凸的关联分析[J].中国脊柱脊髓杂志,2009,19(3)：222-226.
[75]费琦,吴志宏,王以朋等.DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究[J].中国组织工程研究与临床康复,2011,15(37)：7017-7022.
[76]费琦,吴志宏,王以朋等.中国汉族人群WNT3A基因多态性与先天性脊柱侧凸遗传易感性的关系[J].中华医学杂志,2011,91(11)：746-751.
[77]费琦,吴志宏,原所茂等.中国汉族人群PAX1基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2008,88(37)：2597-2602.
[78]费琦,吴志宏,周熹等.中国汉族人群SIM2基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2009,89(41)：2888-2893.
[79]D. B. Sparrow.G. Chapman,S. L. Dunwoodie. The mouse notches up another success:Understanding the causes of human vertebral malformation[J]. Mammalian Genome.2011.22 (7-8):362-376
[80]D. B. Sparrow,G. Chapman,A. J. Smithet al. A mechanism for gene-environment interaction in the etiology of congenital scoliosis[J]. Cell.2012.149 (2):295-306
[81]P. G. Alexander,R. S. Tuan. Role of environmental factors in axial skeletal dysmorphogenesis[J]. Birth Defects Res C Embryo Today.2010.90 (2):118-132
[82]P. G. Alexander.R. S. Tuan. Role of environmental factors in axial skeletal dysmorphogenesis[J]. Birth Defects Research Part C-Embryo Today. Reviews.2010.90 (2):118-132
[83]Z. F. Zakeri,H. S. Ahuja. Cell death/apoptosis:normal, chemically induced, and teratogenic effect[J]. Mutat Res.1997.396 (1-2):149-161
[84]C. Y. Kawanishi,P. Hartig,K. L. Bobseineet al. Axial skeletal and Hox expression domain alterations induced by retinoic acid, valproic acid, and bromoxynil during murine development[J]. J Biochem Mol Toxicol.2003.17 (6):346-356
[85]G. Duester. Retinoic acid regulation of the somitogenesis clock[J]. Birth Defects Res C Embryo Today. 2007.81 (2):84-92
[86]H. Nau,R. S. Hauck,K. Ehlers. Valproic acid-induced neural tube defects in mouse and human:aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms[J]. Pharmacol Toxicol.1991.69 (5).310-321
[87]A. Basu,F. H. Wezeman. Developmental toxicity of valproic acid during embryonic chick vertebral chondrogenesis[J]. Spine (Phila Pa 1976).2000.25 (17):2158-2164
[88]G. L. Barnes,P. G. Alexander,C. W. Hsuet al. Cloning and characterization of chicken Paraxis:a regulator of paraxial mesoderm development and somite formation[J]. Dev Biol.1997.189 (1):95-111
[89]N. D. Greene,A. J. Copp. Mouse models of neural tube defects:investigating preventive mechanisms[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):31-41
[90]K. P. Xu,Y. Li,A. V. Ljubimovet al. High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing[J]. Diabetes.2009.58 (5).1077-1085
[91]A. Aberg,L. Westbonm,B.Kallen. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes[J]. Early Hum Dev.2001.61 (2):85-95
[92]S. Akazawa. Diabetic embryopathy:studies using a rat embryo culture system and an animal model[J]. Congenit Anom (Kyoto).2005.45 (3):73-79
[93]M. R. Loeken. Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):77-87
[94]M. R. Loeken. Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):77-87
[95]A. Ornoy. Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis on diabetic embryopathy[J]. Reprod Toxicol.2007.24 (1):31-41
[96]K. Oyama,Y. Sugimura,T. Muraseet al. Folic acid prevents congenital malformations in the offspring of diabetic mice[J].Endocr J.2009.56 (1):29-37
[97]W. S. Webster,D. Abela. The effect of hypoxia in development[J]. Birth Defects Res C Embryo Today. 2007.81 (3):215-228
[98]J. M. Yon,I. J. Baek,S. R. Leeet al. The spatio-temporal expression pattern of cytoplasmic Cu/Zn superoxide dismutase (SOD1) mRNA during mouse embryogenesis[J]. J Mol Histol.2008.39 (1) 95-103
[99]R. Dumollard,M. Duchen,J. Carroll. The role of mitochondrial function in the oocyte and embryo[J]. Curr Top Dev Biol.2007.77:21-49
[100]J. Singh. Interaction of maternal protein and carbon monoxide on pup mortality in mice:implications for global infant mortality[J]. Birth Defects Res B Dev Reprod Toxicol.2006.77 (3):216-226
[101]M. A. Robkin. Carbon monoxide and the embryo[J]. Int J Dev Biol.1997.41 (2):283-289
[102]J. M. DeSesso,C. F. Jacobson,A. R. Scialliet al. An assessment of the developmental toxicity of inorganic arsenic[J]. Reprod Toxicol.1998.12 (4):385-433
[103]H. Thackray,C. Tifft. Fetal alcohol syndrome[J]. Pediatr Rev.2001.22 (2):47-55
[104]R. Yelin,H.Kot,D. Yelinet al. Early molecular effects of ethanol during vertebrate embryogenesis[J]. Differentiation.2007.75 (5):393-403
[105]J. G. Breen,T. W. Claggett,G. L. Kimmelet al. Heat shock during rat embryo development in vitro results in decreased mitosis and abundant cell death[J]. Reprod Toxicol.1999.13 (1):31-39
[106]JM Jr Graham,M. J. Edwards,M. J. Edwards. Teratogen update:gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans[J]. Teratology.1998.58 (5):209-221
[107]J. A. McCubrey,L. S. Steelman,R. A. Franklinet al. Targeting the RAF/MEK/ERK, PI3K/AKT and p53 pathways in hematopoietic drug resistance[J]. Adv Enzyme Regul.2007.47:64-103
[108]J. A. McCubrey,M. M. Lahair,R. A. Franklin. Reactive oxygen species-induced activation of the MAP kinase signaling pathways[J]. Antioxid Redox Signal.2006.8 (9-10):1775-1789
[109]M. C. Delfini,J. Dubrulle,P. Malapertet al. Control of the segmentation process by graded MAPK/ERK activation in the chick embryo[J]. Proc Natl Acad Sci U S A.2005.102 (32):11343-11348
[110]E. Hodges,Z. Xuan,V. Balijaet al. Genome-wide in situ exon capture for selective resequencing[J]. Nat Genet.2007.39 (12):1522-1527
[111]S. B. Ng,E.H. Turner,P.D. Robertsonet al. Targeted capture and massively parallel sequencing of 12 human exomes[J]. Nature.2009.461 (7261):272-276
[112]J. Shendure,H. Ji. Next-generation DNA sequencing[J]. Nat Biotechnol.2008.26 (10):1135-1145
[113]M. L. Metzker. Sequencing technologies-the next generation[J]. Nat Rev Genet.2010.11(1):31-46
[114]S. B. Ng,A. W. Bigham,K. J. Buckinghamet al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome[J]. Nat Genet.2010.42 (9):790-793
[115]K. Bilguvar,A. K. Ozturk,A. Louviet al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations[J]. Nature.2010.467 (7312):207-210
[116]X. J. Yao,J. Xu,Z. H. Guet al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia[J]. Nat Genet.2011.43 (4):309-315
[117]L. E. Vissers,J. de Ligt,C. Gilissenet al. A de novo paradigm for mental retardation[J]. Nat Genet. 2010.42 (12):1109-1112
[118]B. J. O'Roak,P. Deriziotis,C. Leeet al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations[J]. Nat Genet.2011.43 (6):585-589
[119]B. Xu,J. L. Roos,P. Dexheimeret al. Exome sequencing supports a de novo mutational paradigm for schizophrenia[J]. Nat Genet.2011.43 (9):864-868
[120]P. D. Stenson,M. Mort,E. V. Ballet al. The Human Gene Mutation Database:2008 update[J]. Genome Med.2009.1 (1):13
[121]G. V. Kryukov,L. A. Pennacchio,S.R.Sunyaev. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies[J]. Am J Hum Genet.2007.80 (4):727-739
[122]C. T. Chen,J. C. Wang,B.A. Cohen. The strength of selection on ultraconserved elements in the human genome[J]. Am J Hum Genet.2007.80 (4):692-704
[123]S. B. Ng,K. J. Buckingham,C. Leeet al. Exome sequencing identifies the cause of a mendelian disorder[J]. Nat Genet.2010.42 (1):30-35
[124]L. G. Biesecker. Exome sequencing makes medical genomics a reality[J]. Nat Genet.2010.42 (1) 13-14
[125]M. J. Bamshad,S. B. Ng,A. W. Bighamet al. Exome sequencing as a tool for Mendelian disease gene discovery[J]. Nat Rev Genet.2011.12 (11):745-755
[126]X. Zhang,M. Li,X. J. Zhang. [Exome sequencing and its application][J]. Yi Chuan.2011.33 (8) 847-856
[127]D. Botstein,N. Risch. Discovering genotypes underlying human phenotypes:past successes for mendelian disease, future approaches for complex disease[J]. Nat Genet.2003.33 Suppl:228-237
[128]C. T. Chen,J. C. Wang,B.A. Cohen. The strength of selection on ultraconserved elements in the human genome[J]. Am J Hum Genet.2007.80 (4):692-704
[129]M. Lynch. Rate, molecular spectrum, and consequences of human mutation[J]. Proc Natl Acad Sci U S A.2010.107 (3):961-968
[130]J. C. Roach,G. Glusman,A. F. Smitet al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing[J]. Science.2010.328 (5978).636-639
[131]J. McClellan,M. C. King. Genetic heterogeneity in human disease[J]. Cell.2010.141 (2):210-217
[132]H. Li,R. Durbin. Fast and accurate short read alignment with Burrows-Wheeler transform[J]. Bioinformatics.2009.25 (14):1754-1760
[133]I. A. Adzhubei,S. Schmidt,L. Peshkinet al. A method and server for predicting damaging missense mutations[J]. Nat Methods.2010.7(4):248-249
[134]P. C. Ng,S. Henikoff. SIFT:Predicting amino acid changes that affect protein function[J]. Nucleic Acids Res.2003.31 (13):3812-3814
[135]J. M. Schwarz,C. Rodelsperger,M. Schuelkeet al. MutationTaster evaluates disease-causing potential of sequence alterations[J]. Nat Methods.2010.7(8):575-576
[136]S. Chun,J. C. Fay. Identification of deleterious mutations within three human genomes[J]. Genome Res.2009.19 (9):1553-1561
[137]E. V. Davydov,D. L. Goode,M. Sirotaet al. Identifying a high fraction of the human genome to be under selective constraint using GERP++[J]. PLoS Comput Biol.2010.6 (12):e1001025
[138]A. Megarbane.N. Salem,E. Stephanet al. X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3[J]. Eur J Hum Genet.2000.8(9):704-708
[139]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[140]Y. Bessho,R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[141]W. Wang. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins[J]. Nat Rev Genet.2007.8 (10):735-748
[142]Y. Kee,A.D.D'Andrea. Expanded roles of the Fanconi anemia pathway in preserving genomic stability[J]. Genes Dev.2010.24 (16):1680-1694
[143]F. Vaz,H.Hanenberg,B. Schusteret al. Mutation of the RAD51C gene in a Fanconi anemia-like disorder[J]. Nat Genet. 2010.42 (5):406-409
[144]S. Unal,N. Ozbek,A. Karaet al. Five Fanconi anemia patients with unusual organ pathologies[J]. Am J Hematol.2004.77 (1):50-54
[145]S. Unal,F. Gumruk. Fanconi anemia patient with bilaterally hypoplastic scapula and unilateral winging associated with scoliosis and rib abnormality [J]. J Pediatr Hematol Oncol.2006.28 (9):616-617
[146]J. McGaughran. Klippel-Feil anomaly in Fanconi anemia[J]. Clin Dysmorphol.2003.12 (3):197
[147]R. D. Kennedy,A. D. D'Andrea. The Fanconi Anemia/BRCA pathway:new faces in the crowd[J]. Genes Dev.2005.19 (24):2925-2940
[148]A. R. Meetei,J. P. de Winter,A. L. Medhurstet al. A novel ubiquitin ligase is deficient in Fanconi anemia[J]. Nat Genet.2003.35 (2):165-170
[149]A. R. Meetei,Z. Yan,W. Wang. FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination[J]. Cell Cycle.2004.3 (2):179-181
[150]A. R. Meetei,A. L. Medhurst,C. Linget al. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M[J]. Nat Genet.2005.37 (9):958-963
[151]C. S. Tremblay,F. F. Huang,O. Habiet al. HES1 is a novel interactor of the Fanconi anemia core complex[J]. Blood.2008.112 (5):2062-2070
[152]P. Castella,S. Sawai,K. Nakaoet al. HES-1 repression of differentiation and proliferation in PC12 cells:role for the helix 3-helix 4 domain in transcription repression[J]. Mol Cell Biol.2000.20 (16) 6170-6183
[153]D. Grbavec,S. Stifani. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif[J]. Biochem Biophys Res Commun.1996.223 (3):701-705
[154]C. S. Tremblay,C. C. Huard,F. F. Huanget al. The fanconi anemia core complex acts as a transcriptional co-regulator in hairy enhancer of split 1 signaling[J]. J Biol Chem.2009.284 (20): 13384-13395
[155]S. J. Park,S. L. Ciccone,B.D. Becket al. Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins[J]. J Biol Chem.2004.279 (29):30053-30059
[156]T. Otsuki,Y. Furukawa,K. Ikedaet al. Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex[J]. Hum Mol Genet.2001.10 (23):2651-2660
[157]F. Qiao,A.Moss,G. M. Kupfer. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage-and cell cycle-regulated manner[J]. J Biol Chem.2001.276 (26):23391-23396
[158]M. Castella,R. Pujol,E. Callenet al. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations[J]. Blood.2011.117 (14):3759-3769
[159]N. B. Collins,J. B. Wilson,T. Bushet al. ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function[J]. Blood.2009.113 (10):2181-2190
[160]F. Yuan,L. Qian,X. Zhaoet al. Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms[J]. J Biol Chem.2012.287(7): 4800-4807
[161]Y. Masamizu,T. Ohtsuka,Y. Takashimaet al. Real-time imaging of the somite segmentation clock: revelation of unstable oscillators in the individual presomitic mesoderm cells[J]. Proc Natl Acad Sci U S A. 2006.103 (5):1313-1318
[162]J. K. Dale,M. Maroto. A Hesl-based oscillator in cultured cells and its potential implications for the segmentation clock[J]. Bioessays.2003.25 (3):200-203
[163]N. A. Monk. Oscillatory expression of Hesl, p53, and NF-kappaB driven by transcriptional time delays[J]. Curr Biol.2003.13 (16):1409-1413
[164]K. Takebayashi,Y. Sasai,Y. Sakaiet al. Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements[J]. J Biol Chem.1994.269 (7):5150-5156
[165]S. Agrawal,C. Archer,D. V. Schaffer. Computational models of the Notch network elucidate mechanisms of context-dependent signaling[J]. PLoS Comput Biol.2009.5(5):e1000390
[166]J. H. Baek,J. Hatakeyama,S. Sakamotoet al. Persistent and high levels of Hesl expression regulate boundary formation in the developing central nervous system[J]. Development.2006.133 (13) 2467-2476
[167JH. Shimojo,T. Ohtsuka,R. Kageyama. Oscillations in notch signaling regulate maintenance of neural progenitors[J]. Neuron.2008.58 (1):52-64
[168]M. Ishibashi.S. L. Ang,K Shiotaet al. Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects[J]. Genes Dev.1995.9 (24):3136-3148
[169]Y. Bessho,R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[170]Y. Niwa,Y. Masamizu,T. Liuet al. The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock[J]. Dev Cell.2007.13 (2):298-304
[171]J. E. Bedard,J. D. Purnell,S. M. Ware. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3[J]. Hum Mol Genet.2007.16 (2):187-198
[172]L. Zhu,G. Zhou,S. Pooleet al. Characterization of the interactions of human ZIC3 mutants with GLI3[J]. Hum Mutat.2008.29 (1):99-105
[173]S. M. Ware,K. G. Harutyunyan J. W. Belmont. Zic3 is critical for early embryonic patterning during gastrulation[J]. Dev Dyn.2006.235 (3):776-785
[174]T. Kitaguchi.T. Nagai,K. Nakataet al. Zic3 is involved in the left-right specification of the Xenopus embryo[J]. Development.2000.127 (22):4787-4795
[175]G. E. Herman,H. M. El-Hodiri. The role of ZIC3 in vertebrate development[J]. Cytogenet Genome Res.2002.99 (1-4):229-235
[176]M. J. Keller,A. B. Chitnis. Insights into the evolutionary history of the vertebrate zic3 locus from a teleost-specific zic6 gene in the zebrafish, Danio rerio[J]. Dev Genes Evol.2007.217 (7):541-547
[177]A. R. McMahon,C. S. Merzdorf. Expression of the zicl, zic2, zic3, and zic4 genes in early chick embryos[J]. BMC Res Notes.2010.3:167
[178]S. M. Ware,J. Peng,L. Zhuet al. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects[J]. Am J Hum Genet.2004.74 (1):93-105
[179]L. Zhu,J. W. Belmont,S. M. Ware. Genetics of human heterotaxias[J]. Eur J Hum Genet.2006.14 (1): 17-25
[180]G. B. Ferrero,M. Gebbia,G. Piliaet al. A submicroscopic deletion in Xq26 associated with familial situs ambiguus[J]. Am J Hum Genet.1997.61 (2):395-401
[181]R. Klootwijk,B. Franke,C. E. van der Zeeet al. A deletion encompassing Zic3 in bent tail, a mouse model for X-linked neural tube defects[J]. Hum Mol Genet.2000.9 (11):1615-1622
[182]J. B. Wallingford,R. M. Harland. Neural tube closure requires Dishevelled-dependent convergent extension of the midline[J]. Development.2002.129 (24):5815-5825
[183]B. Chung,L. G. Shaffer,S. Keatinget al. From VACTERL-H to heterotaxy:variable expressivity of ZIC3-related disorders[J]. Am J Med Genet A.2011.155A (5):1123-1128
[184]L. Ma,Tierney ES Selamet,T. Leeet al. Mutations in ZIC3 and ACVR2B are a common cause of heterotaxy and associated cardiovascular anomalies[J].Cardiol Young.2012.22 (2):194-201
[185]F. C. Wardle,V. E. Papaioannou. Teasing out T-box targets in early mesoderm[J]. Curr Opin Genet Dev.2008.18 (5):418-425
[186]L. M. Goering,K. Hoshijima,B. Huget al. An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm[J]. Proc Natl Acad Sci U S A.2003.100 (16):9410-9415
[187]D. L. Chapman,V. E. Papaioannou. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6[J]. Nature.1998.391 (6668):695-697
[188]J. Beckers,N. Schlautmann,A.Gossler. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Deltal null allele[J]. Mech Dev.2000.95 (1-2):35-46
[189]Y. Yasuhiko.S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[190]P. H. White,D. R. Farkas,E.E.McFaddenet al. Defective somite patterning in mouse embryos with reduced levels of Tbx6[J]. Development.2003.130 (8):1681-1690
[191]Y. Shen,X. Chen,L. Wanget al. Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family[J]. Am J Med Genet B Neuropsychiatr Genet.2011.156 (2):225-232
[1]M. J. McMaster,K. Ohtsuka. The natural history of congenital scoliosis. A study of two hundred and fifty-one patients[J]. J Bone Joint Surg Am.1982.64 (8):1128-1147
[2]AR Jr SHANDS,H. B. EISBERG. The incidence of scoliosis in the state of Delaware; a study of 50,000 minifilms of the chest made during a survey for tuberculosis[J]. J Bone Joint Surg Am.1955.37-A (6) 1243-1249
[3]M. J. McMaster,H.Singh. Natural history of congenital kyphosis and kyphoscoliosis. A study of one hundred and twelve patients[J]. J Bone Joint Surg Am.1999.81 (10):1367-1383
[4]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. JMed Genet. 1975.12 (3):280-288
[5]D. Jaskwhich,R. M. Ali,T. C. Patelet al. Congenital scoliosis[J]. CURRENT OPINION IN PEDIATRICS.2000.12 (1):61-66
[6]D. Hedequist,J. Emans. Congenital scoliosis:a review and update[J]. J Pediatr Orthop.2007.27 (1) 106-116
[7]A. Offiah,B. Alman,A. S. Cornieret al. Pilot assessment of a radiologic classification system for segmentation defects of the vertebrae[J]. Am J Med Genet A.2010.152A (6):1357-1371
[8]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[9]G. H. Shahcheraghi,M. H. Hobbi. Patterns and progression in congenital scoliosis[J]. J Pediatr Orthop. 1999.19 (6):766-775
[10]J. M. Connor,A. N. Conner,R. A. Connoret al. Genetic aspects of early childhood scoliosis[J]. Am J Med Genet.1987.27 (2):419-424
[11]S. B. Purkiss,B.Driscoll,W. G. Coleet al. Idiopathic scoliosis in families of children with congenital scoliosis[J]. Clin Orthop Relat Res.2002 (401):27-31
[12]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. JMed Genet.1975.12 (3):280-288
[13]M. L. Martinez-Frias,E. Bermejo,L. Paisanet al. Severe spondylocostal dysostosis associated with other congenital anomalies:a clinical/epidemiologic analysis and description of ten cases from the Spanish registry[J]. Am J Med Genet.1994.51 (3):203-212
[14]D. B. Sparrow,G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[15]D. B. Sparrow,E. Guillen-Navarro,D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[16]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[17]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[18]P. Lorenz,E. Rupprecht. Spondylocostal dysostosis:dominant type[J]. Am J Med Genet.1990.35 (2): 219-221
[19]P. D. Turnpenny,R. J. Thwaites,F. N. Boulos. Evidence for variable gene expression in a large inbred kindred with autosomal recessive spondylocostal dysostosis[J]. J Med Genet.1991.28 (1):27-33
[20]S. L. Dunwoodie,D. Henrique.S. M. Harrisonet al. Mouse D113:a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo[J]. Development.1997.124 (16):3065-3076
[21]K. Kusumi,E. S. Sun,A. W. Kerrebrocket al. The mouse pudgy mutation disrupts Delta homologue D113 and initiation of early somite boundaries[J]. Nat Genet.1998.19 (3):274-278
[22]P. D. Turnpenny,B. Alman,A. S. Cornieret al. Abnormal vertebral segmentation and the notch signaling pathway in man[J]. Dev Dyn.2007.236 (6):1456-1474
[23]S. L. Dunwoodie,M. Clements,D. B. Sparrowet al. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene D113 are associated with disruption of the segmentation clock within thepresomitic mesoderm[J]. Development.2002.129 (7):1795-1806
[24]K. Kusumi,M. S. Mimoto,K. L. Covelloet al. D113 pudgy mutation differentially disrupts dynamic expression of somite genes[J]. Genesis.2004.39 (2):115-121
[25]I. B. Barrantes,A. J. Elia,K. Wunschet al. Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse[J]. Curr Biol.1999.9(9):470-480
[26]G. F. Hoyne,G. Chapman,Y. Sontaniet al. A cell autonomous role for the Notch ligand Delta-like 3 in alphabeta T-cell development[J]. Immunol Cell Biol.2011.89 (6).696-705
[27]G. Chapman,D. B. Sparrow,E. Kremmeret al. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis[J]. Hum Mol Genet.2011. 20 (5):905-916
[28]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[29]M. Morimoto,Y. Takahashi,M. Endoet al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity[J]. Nature.2005.435 (7040):354-359
[30]M. Morimoto,N. Sasaki,M. Oginumaet al. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite[J]. Development.2007.134 (8); 1561-1569
[31]Y. Yasuhiko.S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[32]A. S. Cornier.K. Staehling-Hampton,K. M. Delventhalet al. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome[J]. Am J Hum Genet.2008.82 (6):1334-1341
[33]N. Zhang,C. R. Norton,T. Gridley. Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice[J]. Genesis.2002.33 (1):21-28
[34]K. Bruckner,L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[35]L. T. Yang,J. T. Nichols,C. Yaoet al. Fringe glycosyltransferases differentially modulate Notchl proteolysis induced by Deltal and Jaggedl [J]. Mol Biol Cell.2005.16 (2):927-942
[36]J. Chen,L. Kang,N. Zhang. Negative feedback loop formed by Lunatic fringe and Hes7 controls their oscillatory expression during somitogenesis[J]. Genesis.2005.43 (4):196-204
[37]D. B. Sparrow,D. Sillence,M. A. Wouterset al. Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis[J]. Eur J Hum Genet. 2010.18 (6):674-679
[38]Y. Floman. "Mirror image" congenital scoliosis in siblings[J]. J Spinal Disord.1991.4 (3):366-368
[39]M. K. Maisenbacher,J. S. Han,M. L. O'Brienet al. Molecular analysis of congenital scoliosis:a candidate gene approach[J]. Hum Genet.2005.116 (5):416-419
[40]N. Ghebranious,C. L. Raggio,R. D. Blanket al. Lack of evidence of WNT3A as a candidate gene for congenital vertebral malformations[J]. Scoliosis.2007.2:13
[41]P. F. Giampietro,S. L. Dunwoodie,K. Kusumiet al. Progress in the Understanding of the Genetic Etiology of Vertebral Segmentation Disorders in Humans G-2911-2010[M]. OXFORD、:BLACKWELL PUBLISHING,2009:38-67
[42]Q. Fei,Z. Wu,H. Wanget al. The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population[J]. Spine (Phila Pa 1976).2010.35 (9):983-988
[43]O. Pourquie. Vertebrate segmentation:from cyclic gene networks to scoliosis[J]. Cell.2011.145 (5): 650-663
[44]费琦,吴志宏,王以朋等LMX1A基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联[J].中国组织工程研究与临床康复,2011,15(35)：6632-6638.
[45]原所茂,吴志宏,魏斌等.HES7基因多态性与先天性脊柱侧凸的关联分析[J].中国脊柱脊髓杂志,2009,19(3)：222-226.
[46]费琦,吴志宏,王以朋等.DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究[J].中国组织工程研究与临床康复,2011,15(37)：7017-7022.
[47]费琦,吴志宏,王以朋等.中国汉族人群WNT3A基因多态性与先天性脊柱侧凸遗传易感性的关系[J].中华医学杂志,2011,91(11)：746-751.
[48]费琦,吴志宏,原所茂等.中国汉族人群PAX1基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2008,88(37)：2597-2602.
[49]费琦,吴志宏,周熹等.中国汉族人群SIM2基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2009,89(41)：2888-2893.
[50]J. Wallin,J. Wilting,H. Kosekiet al. The role of Pax-1 in axial skeleton development[J]. Development. 1994.120 (5):1109-1121
[51]J. M. McGaughran,A.Oates,D. Donnaiet al. Mutations in PAX1 may be associated with Klippel-Feil syndrome[J]. EUROPEAN JOURNAL OF HUMAN GENETICS.2003.11 (6):468-474
[52]P. F. Giampietro,C. L. Raggio,C. E. Reynoldset al. An analysis of PAX1 in the development of vertebral malformations[J]. Clin Genet.2005.68 (5):448-453
[53]C. Farrington-Rock,V. Kirilova,L. Dillard-Telmet al. Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome[J]. Hum Mol Genet.2008.17 (5):631-641
[54]M. B. Dobbs,S. Boehm,D. K. Grangeet al. Case report:Congenital knee dislocation in a patient with larsen syndrome and a novel filamin B mutation[J]. Clin Orthop Relat Res.2008.466 (6):1503-1509
[55]L. S. Bicknell,C. Farrington-Rock,Y. Shafeghatiet al. A molecular and clinical study of Larsen syndrome caused by mutations in FLNB[J]. J Med Genet.2007.44 (2):89-98
[56]C. Goumy,A. M. Beaufrere,A. Tchirkovet al. Larsen-like phenotype associated with partial trisomy 3p and monosomy 5p[J]. Prenat Diagn.2008.28 (2):131-134
[57]J. Lu,G. Lian,R. Lenkinskiet al. Filamin B mutations cause chondrocyte defects in skeletal development[J]. Hum Mol Genet.2007.16 (14):1661-1675
[58]M. Colombani,N. Laurent,M. Le Merreret al. A new osteochondrodysplasia with severe osteopenia, preaxial polydactyly, clefting and dysmorphic features resembling filamin-related disorders[J]. Prenat Diagn.2006.26 (12):1151-1155
[59]C. Farrington-Rock,M. H. Firestein,L. S. Bicknellet al. Mutations in two regions of FLNB result in atelosteogenesis Ⅰ and Ⅲ[J].Hum Mutat.2006.27 (7):705-710
[60]D. Krakow.S. P. Robertson,L. M. Kinget al. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis[J]. Nat Genet.2004.36 (4):405-410
[61]L. S. Bicknell,T. Morgan,L. Bonafeet al. Mutations in FLNB cause boomerang dysplasia[J]. J Med Genet.2005.42 (7):e43
[62]G. Weinmaster.C. Kintner. Modulation of Notch signaling during somitogenesis[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY.2003.19:367-395
[63]G. Chapman,D. B. Sparrow,E. Kremmeret al. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis[J]. Hum Mol Genet.2011. 20 (5):905-916
[64]G. F. Hoyne,G. Chapman,Y. Sontaniet al. A cell autonomous role for the Notch ligand Delta-like 3 in alphabeta T-cell development[J]. Immunol Cell Biol.2011.89 (6):696-705
[65]S. L. Dunwoodie,D. Henrique,S. M. Harrisonet al. Mouse D113:a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo[J]. Development.1997.124 (16):3065-3076
[66]K. Kusumi,E. S. Sun,A. W. Kerrebrocket al. The mouse pudgy mutation disrupts Delta homologue D113 and initiation of early somite boundaries[J]. Nat Genet. 1998.19 (3):274-278
[67]S. L. Dunwoodie,M. Clements,D. B. Sparrowet al. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene D113 are associated with disruption of the segmentation clock within the presomitic mesoderm[J]. Development.2002.129 (7):1795-1806
[68]P. F. Giampietro,C. L. Raggio,R. D. Blank. Synteny-defined candidate genes for congenital and idiopathic scoliosis[J]. Am J Med Genet.1999.83 (3):164-177
[69]P. D. Turnpenny,M. P. Bulman,T. M. Fraylinget al. A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3[J]. Am J Hum Genet.1999.65 (1):175-182
[70]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[71]R. E. Fisher,H. F. Smith,K. Kusumiet al. Mutations in the Notch Pathway Alter the Patterning of Multifidus[J]. Anat Rec (Hoboken).2011:
[72JN. V. Whittock,S. Ellard,J. Duncanet al. Pseudodominant inheritance of spondylocostal dysostosis type 1 caused by two familial delta-like 3 mutations[J]. CLINICAL GENETICS.2004.66 (1):67-72
[73]P. F. Giampietro,C. L. Raggio,C. Reynoldset al. DLL3 as a candidate gene for vertebral malformations[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A.2006.140A (22) 2447-2453
[74]K. M.Loomes,S. A. Stevens,M. L. O'Brienet al. Dll3 and Notchl genetic interactions model axial segmental and craniofacial malformations of human birth defects C-5418-2011 [J]. DEVELOPMENTAL DYNAMICS.2007.236 (10):2943-2951
[75]Y. Yasuhiko,S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[76]M. Morimoto,Y. Takahashi,M. Endoet al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity[J]. Nature.2005.435 (7040):354-359
[77]M. Morimoto,N. Sasaki,M. Oginumaet al. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite[Jj. Development.2007.134 (8) 1561-1569
[78]N. Sasaki,M. Kiso,M. Kitagawaet al. The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis[J]. Development.2011.138 (1):55-64
[79]M. Morimoto,M. Kiso,N. Sasakiet al. Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis[J]. Dev Biol.2006.300 (2):687-698
[80]C. Rallis.S. M. Pinchin,D. Ish-Horowicz. Cell-autonomous integrin control of Wnt and Notch signalling during somitogenesis[J]. Development.2010.137 (21):3591-3601
[81]M. Oginuma,Y. Takahashi,S. Kitajimaet al. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite[J]. Development.2010. 137 (9):1515-1522
[82]Y. Saga,N. Hata,H. Kosekiet al. Mesp2:a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation[J]. Genes Dev.1997.11 (14):1827-1839
[83]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans B-3994-2008 F-4310-2010[J]. AMERICAN JOURNAL OF HUMAN GENETICS.2004.74 (6):1249-1254
[84]A. S. Cornier,K. Staehling-Hampton,K. M. Delventhalet al. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome[J]. Am J Hum Genet.2008.82 (6):1334-1341
[85]E. Goshu,H. Jin,R. Fasnachtet al. Sim2 mutants have developmental defects not overlapping with those of Siml mutants[J]. Mol Cell Biol.2002.22 (12):4147-4157
[86]Q. Fei,Z. H. Wu,X. Zhouet al. [Association study of SIM2 gene polymorphisms with susceptibility to congenital scoliosis in a Chinese Han population][J]. Zhonghua Yi Xue Za Zhi.2009.89 (41):2888-2893
[87]R. Nusse,H. E. Varmus. Wnt genes[J]. Cell.1992.69 (7):1073-1087
[88]S. Takada,K. L. Stark,M. J. Sheaet al. Wnt-3a regulates somite and tailbud formation in the mouse embryo[J]. Genes Dev.1994.8 (2):174-189
[89]WC Jr Dunty,K. K. Biris,R. B. Chalamalasettyet al. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation[J]. Development.2008.135 (1):85-94
[90]R. B. Chalamalasetty,W. C. Dunty Jr.,K. K. Biriset al. The Wnt3a/(beta)-catenin target gene Mesogeninl controls the segmentation clock by activating a Notch signalling program[J]. Nature Communications.2011.2 (1):
[91]V. E. Papaioannou. T-box genes in development:from hydra to humans[J]. Int Rev Cytol.2001.207: 1-70
[92]D. L. Chapman,V. E. Papaioannou. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6[J]. Nature.1998.391 (6668):695-697
[93]P. H. White,D. R. Farkas,E. E. McFaddenet al. Defective somite patterning in mouse embryos with reduced levels of Tbx6[J]. Development.2003.130 (8):1681-1690
[94]J. Beckers,N. Schlautmann,A. Gossler. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Deltal null allele[J]. Mech Dev.2000.95 (1-2):35-46
[95]Y. Yasuhiko.S. Kitajima,Y. Takahashiet al. Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2[J]. Development.2008.135 (21) 3511-3519
[96]M. Oginuma,Y. Niwa,D. L. Chapmanet al. Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis[J]. Development.2008.135 (15) 2555-2562
[97]Y. Shen,X. Chen,L. Wanget al. Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family[J]. Am J Med Genet B Neuropsychiatr Genet.2011.156 (2):225-232
[98]J. Klingensmith,Y. Yang,J. D. Axelrodet al. Conservation of dishevelled structure and function between flies and mice:isolation and characterization of Dvl2[J]. Mech Dev.1996.58 (1-2):15-26
[99]N. S. Hamblet,N. Lijam,P. Ruiz-Lozanoet al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure[J]. Development.2002.129 (24):5827-5838
[100]J. H. Millonig,K. J. Millen,M. E. Hatten. The mouse Dreher gene Lmxla controls formation of the roof plate in the vertebrate CNS[J]. Nature.2000.403 (6771):764-769
[101]V. Chizhikov,E.Steshina,R. Robertset al. Molecular definition of an allelic series of mutations disrupting the mouse Lmxla (dreher) gene[J]. Mamm Genome.2006.17 (10):1025-1032
[102]K. Bruckner,L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[103]D. J. Moloney.V. M. Panin,S. H. Johnstonet al. Fringe is a glycosyltransferase that modifies Notch[J]. Nature.2000.406 (6794):369-375
[104]N. Haines,K. D. Irvine. Glycosylation regulates Notch signalling[J]. Nat Rev Mol Cell Biol.2003.4 (10):786-797
[105]N. Zhang,T. Gridley. Defects in somite formation in lunatic fringe-deficient mice[J]. Nature.1998. 394 (6691):374-377
[106]D. B. Sparrow,G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[107]R. L. Davis,D. L. Turner. Vertebrate hairy and Enhancer of split related proteins:transcriptional repressors regulating cellular differentiation and embryonic patterning[J]. Oncogene.2001.20 (58) 8342-8357
[108]A. Fischer,M. Gessler. Delta-Notch-and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors[J]. Nucleic Acids Res.2007.35 (14):4583-4596
[109]Y. Bessho,H. Hirata,Y. Masamizuet al. Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock[J]. Genes Dev.2003.17 (12):1451-1456
[110]Y. Bessho.R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[111]R. Kageyama,Y. Niwa,H.Shimojoet al. Ultradian oscillations in Notch signaling regulate dynamic biological events[J]. Current Topics in Developmental Biology.2010.92 (C):311-331
[112]Y. Takashima,T. Ohtsuka,A. Gonzalezet al. Intronic delay is essential for oscillatory expression in the segmentation clock[J]. Proceedings of the National Academy of Sciences of the United States of America. 2011.108 (8):3300-3305
[113]D. B. Sparrow,E.Guillen-Navarro.D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[114]D. B. Sparrow,D. Sillence,M. A. Wouterset al. Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis[J]. Eur J Hum Genet. 2010.18 (6):674-679
[115]Y. Xue,X. Gao,C. E. Lindsellet al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1[J]. Hum Mol Genet.1999.8 (5):723-730
[116]T. Oda,A. G. Elkahloun,B. L. Pikeet al. Mutations in the human Jaggedl gene are responsible for Alagille syndrome[J]. Nat Genet.1997.16 (3):235-242
[117]C. Glaser.S. Schulz,C. Schmidtet al. Nonrandom distribution of JAG 1 mutations in patients with alagille syndrome[J]. Medizinische Genetik.2011.23 (1):106
[118]A. Cosme,A.M. Cobo,M. Meunier-Rotivalet al. Molecular and clinical characteristics of a family with Alagille syndrome[J]. Medicina Clinica.2008.130 (1):17-19
[119]C. Lertudomphonwanit,S. Treepongkaruna,D. Charoenpipopet al. Phenotypes and genotypes of alagille syndrome in thai children:Report of 4 cases[J]. Hepatology International.2011.5(1):394
[120]R. McDaniell,D. M. Warthen,P. A. Sanchez-Laraet al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway[J]. Am J Hum Genet.2006.79 (1):169-173
[121]C. Zweier.G. Hammersen,R. Behrenset al. Severe course of alagille syndrome associated with a novel NOTCH2 mutation[J]. Genetic Counseling.2010.21 (1):132-133
[122]C. Schmidt,D. Wandt,S. Schulzet al. NOTCH2 mutations in patients with Alagille syndrome[J]. Medizinische Genetik.2010.22 (1):122
[123]P. D. Turnpenny,S. Ellard. Alagille syndrome:pathogenesis, diagnosis and management[J]. Eur J Hum Genet.2011:
[2]AR Jr SHANDS,H. B. EISBERG. The incidence of scoliosis in the state of Delaware; a study of 50,000 minifilms of the chest made during a survey for tuberculosis[J]. J Bone Joint Surg Am.1955.37-A (6): 1243-1249
[3]M. J. McMaster,H. Singh. Natural history of congenital kyphosis and kyphoscoliosis. A study of one hundred and twelve patients[J]. J Bone Joint Surg Am.1999.81 (10):1367-1383
[4]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[5]D. Jaskwhich,R. M. Ali,T. C. Patelet al. Congenital scoliosis[J]. CURRENT OPINION IN PEDIATRICS.2000.12 (1):61-66
[6]D. Hedequist,J. Emans. Congenital scoliosis:a review and update[J]. J Pediatr Orthop.2007.27 (1) 106-116
[7]A. Offiah,B. Alman,A. S. Cornieret al. Pilot assessment of a radiologic classification system for segmentation defects of the vertebrae[J]. Am J Med Genet A.2010.152A (6):1357-1371
[8]M. L. Dequeant,O. Pourquie. Segmental patterning of the vertebrate embryonic axis[J]. NATURE REVIEWS GENETICS.2008.9 (5):370-382
[9]N. Cambray,V. Wilson. Two distinct sources for a population of maturing axial progenitors[J]. Development.2007.134 (15):2829-2840
[10]E. Tzouanacou,A. Wegener.F. J. Wymeerschet al. Redefining the progression of lineage segregations during mammalian embryogenesis by clonal analysis[J]. Dev Cell.2009.17 (3):365-376
[11]A. Aulehla,W. Wiegraebe,V. Baubetet al. A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation[J]. Nat Cell Biol.2008.10 (2):186-193
[12]I. Palmeirim,S. Rodrigues,J. K. Daleet al. Development on time[J]. Adv Exp Med Biol.2008.641: 62-71
[13]C. Schroter,L. Herrgen,A. Cardonaet al. Dynamics of zebrafish somitogenesis[J]. Dev Dyn.2008.237 (3):545-553
[14]S. A. Holley. The genetics and embryology of zebrafish metamerism[J]. Dev Dyn.2007.236 (6) 1422-1449
[15]I. Bothe,M. U. Ahmed,F. L. Winterbottomet al. Extrinsic versus intrinsic cues in avian paraxial mesoderm patterning and differentiation[J]. Dev Dyn.2007.236 (9):2397-2409
[16]O. Pourquie. Vertebrate segmentation:from cyclic gene networks to scoliosis[J]. Cell.2011.145 (5) 650-663
[17]P. C. Rida,N. Le Minh,Y. J. Jiang. A Notch feeling of somite segmentation and beyond[J]. Dev Biol. 2004.265 (1):2-22
[18]Z. Ferjentsik,S. Hayashi,J. K. Daleet al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites[J]. PLoS Genet.2009.5(9):e1000662
[19]S. Gibb,M. Maroto,J. K. Dale. The segmentation clock mechanism moves up a notch[J]. Trends Cell Biol.2010.20 (10):593-600
[20]K. Bruckner.L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[21]D. J. Moloney,V. M. Panin,S. H. Johnstonet al. Fringe is a glycosyltransferase that modifies Notch[J]. Nature.2000.406 (6794):369-375
[22]G. Weinmaster,C. Kintner. Modulation of Notch signaling during somitogenesis[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY.2003.19:367-395
[23]R. T. Moon,A. D. Kohn,G. V. De Ferrariet al. WNT and beta-catenin signalling:diseases and therapies[J]. Nat Rev Genet.2004.5 (9):691-701
[24]H. Huang,X. He. Wnt/beta-catenin signaling:new (and old) players and new insights[J]. Curr Opin Cell Biol.2008.20 (2):119-125
[25]L. Ciani,P. C. Salinas. WNTs in the vertebrate nervous system:from patterning to neuronal connectivity [J]. Nat Rev Neurosci.2005.6(5):351-362
[26]W. Lu,V. Yamamoto,B.Ortegaet al. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth[J]. Cell.2004.119 (1):97-108
[27]Y. Zou. Wnt signaling in axon guidance[J]. Trends Neurosci.2004.27 (9):528-532
[28]M. Kuhl,L.C. Sheldahl,C. C. Malbonet al. Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus[J]. J Biol Chem. 2000.275 (17):12701-12711
[29]A. D. Kohn,R. T. Moon. Wnt and calcium signaling:beta-catenin-independent pathways[J]. Cell Calcium.2005.38 (3-4):439-446
[30]M. V. Semenov,R. Habas,B. T. Macdonaldet al. SnapShot:Noncanonical Wnt Signaling Pathways[J]. Cell.2007.131 (7):1378
[31]H. Takahashi,F. C. Liu. Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors[J]. Birth Defects Res C Embryo Today.2006.78 (3):256-266
[32]C. H. Kim,T. Oda,M. Itohet al. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation[J]. Nature.2000.407 (6806):913-916
[33]H. Popperl,C. Schmidt,V. Wilsonet al. Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm[J]. Development.1997.124 (15): 2997-3005
[34]N. S. Hamblet,N. Lijam,P. Ruiz-Lozanoet al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure[J]. Development. 2002.129 (24):5827-5838
[35]L. Zeng,F. Fagotto,T. Zhanget al. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation[J]. Cell.1997.90 (1):181-192
[36]M. Carter,X. Chen,B.Slowinskaet al. Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6[J]. Proc Natl Acad Sci U S A. 2005.102 (36):12843-12848
[37]C. Kokubu,U. Heinzmann,T. Kokubuet al. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis[J]. Development.2004.131 (21):5469-5480
[38]M. L. Dequeant,E.Glynn,K. Gaudenzet al. A complex oscillating network of signaling genes underlies the mouse segmentation clock[J]. Science.2006.314 (5805):1595-1598
[39]A. Kawamura.S. Koshida,H.Hijikataet al. Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites[J]. Genes Dev.2005.19 (10) 1156-1161
[40]P. H. Crossley,S. Martinez,G. R. Martin. Midbrain development induced by FGF8 in the chick embryo[J]. Nature.1996.380 (6569):66-68
[41]H. Shamim,R. Mahmood,C. Loganet al. Sequential roles for Fgf4, Enl and Fgf8 in specification and regionalisation of the midbrain[J]. Development.1999.126 (5):945-959
[42]T. Fukuchi-Shimogori,E. A. Grove. Neocortex patterning by the secreted signaling molecule FGF8[J]. Science.2001.294 (5544):1071-1074
[43]A. Aulehla,C. Wehrle,B. Brand-Saberiet al. Wnt3A plays a major role in the segmentation clock controlling somitogenesis[J]. DEVELOPMENTAL CELL.2003.4 (3):395-406
[44]I. Palmeirim,D. Henrique,D. Ish-Horowiczet al. Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis[J]. Cell.1997.91 (5):639-648
[45]P. C. Rida,N. Le Minh,Y. J. Jiang. A Notch feeling of somite segmentation and beyond[J]. Dev Biol. 2004.265 (1):2-22
[46]A. Aulehla,C. Wehrle,B.Brand-Saberiet al. Wnt3a plays a major role in the segmentation clock controlling somitogenesis[J]. Dev Cell.2003.4 (3):395-406
[47]M. Hofmann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[48]M. Hofinann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dlll expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[49]M. Hofmann,K. Schuster-Gossler,M. Watabe-Rudolphet al. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dlll expression in the presomitic mesoderm of mouse embryos[J]. Genes Dev.2004.18 (22):2712-2717
[50]S. Gibb,A.Zagorska,K. Meltonet al. Interfering with Wnt signalling alters the periodicity of the segmentation clock[J]. Dev Biol.2009.330 (1):21-31
[51]M. B. Wahl,C. Deng,M. Lewandoskiet al. FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis[J]. Development. 2007.134 (22):4033-4041
[52]J. Dubrulle,M. J. McGrew,O. Pourquie. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation[J]. Cell.2001.106 (2):219-232
[53]A. Sawada,A. Fritz,Y. J. Jianget al. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites[J]. Development.2000.127 (8):1691-1702
[54]Y. Niwa,H. Shimojo,A. Isomuraet al. Different types of oscillations in Notch and Fgf signaling regulate the spatiotemporal periodicity of somitogenesis[J]. Genes Dev.2011.25 (11):1115-1120
[55]WC Jr Dunty,K. K. Biris,R. B. Chalamalasettyet al. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation[J]. Development.2008.135 (1):85-94
[56]J. K. Dale,P. Malapert,J. Chalet al. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis[J]. Dev Cell.2006.10(3): 355-366
[57]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cysticafJ]. J Med Genet.1975.12 (3):280-288
[58]G. H. Shahcheraghi,M. H. Hobbi. Patterns and progression in congenital scoliosis[J]. J Pediatr Orthop. 1999.19 (6):766-775
[59]J. M. Connor,A.N. Conner,R. A. Connoret al. Genetic aspects of early childhood scoliosis[J]. Am J Med Genet.1987.27 (2):419-424
[60]S. B. Purkiss,B. Driscoll,W. G. Coleet al. Idiopathic scoliosis in families of children with congenital scoliosis[J]. Clin Orthop Relat Res.2002 (401):27-31
[61]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[62]M. L. Martinez-Frias,E. Bermejo.L.Paisanet al. Severe spondylocostal dysostosis associated with other congenital anomalies:a clinical/epidemiologic analysis and description of ten cases from the Spanish registry[J]. Am J Med Genet.1994.51 (3):203-212
[63]D. B. Sparrow.G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[64]D. B. Sparrow,E. Guillen-Navarro,D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[65]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[66]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[67]P. Lorenz,E. Rupprecht. Spondylocostal dysostosis:dominant type[J]. Am J Med Genet.1990.35(2): 219-221
[68]Y. Floman. "Mirror image" congenital scoliosis in siblings[J]. J Spinal Disord.1991.4 (3):366-368
[69]N. Ghebranious,C. L. Raggio,R. D. Blanket al. Lack of evidence of WNT3A as a candidate gene for congenital vertebral malformations[J]. Scoliosis.2007.2:13
[70]M. K. Maisenbacher,J. S. Han,M. L. O'Brienet al. Molecular analysis of congenital scoliosis:a candidate gene approach[J]. Hum Genet.2005.116 (5):416-419
[71]P. F. Giampietro,S. L. Dunwoodie,K. Kusumiet al. Progress in the Understanding of the Genetic Etiology of Vertebral Segmentation Disorders in Humans G-2911-2010[M]. OXFORD,:BLACKWELL PUBLISHING,2009:38-67
[72]Q. Fei,Z. Wu,H. Wanget al. The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population[J]. Spine (Phila Pa 1976).2010.35 (9):983-988
[73]费琦,吴志宏,王以朋等LMX1A基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联[J].中国组织工程研究与临床康复,2011,15(35)：6632-6638.
[74]原所茂,吴志宏,魏斌等.HES7基因多态性与先天性脊柱侧凸的关联分析[J].中国脊柱脊髓杂志,2009,19(3)：222-226.
[75]费琦,吴志宏,王以朋等.DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究[J].中国组织工程研究与临床康复,2011,15(37)：7017-7022.
[76]费琦,吴志宏,王以朋等.中国汉族人群WNT3A基因多态性与先天性脊柱侧凸遗传易感性的关系[J].中华医学杂志,2011,91(11)：746-751.
[77]费琦,吴志宏,原所茂等.中国汉族人群PAX1基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2008,88(37)：2597-2602.
[78]费琦,吴志宏,周熹等.中国汉族人群SIM2基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2009,89(41)：2888-2893.
[79]D. B. Sparrow.G. Chapman,S. L. Dunwoodie. The mouse notches up another success:Understanding the causes of human vertebral malformation[J]. Mammalian Genome.2011.22 (7-8):362-376
[80]D. B. Sparrow,G. Chapman,A. J. Smithet al. A mechanism for gene-environment interaction in the etiology of congenital scoliosis[J]. Cell.2012.149 (2):295-306
[81]P. G. Alexander,R. S. Tuan. Role of environmental factors in axial skeletal dysmorphogenesis[J]. Birth Defects Res C Embryo Today.2010.90 (2):118-132
[82]P. G. Alexander.R. S. Tuan. Role of environmental factors in axial skeletal dysmorphogenesis[J]. Birth Defects Research Part C-Embryo Today. Reviews.2010.90 (2):118-132
[83]Z. F. Zakeri,H. S. Ahuja. Cell death/apoptosis:normal, chemically induced, and teratogenic effect[J]. Mutat Res.1997.396 (1-2):149-161
[84]C. Y. Kawanishi,P. Hartig,K. L. Bobseineet al. Axial skeletal and Hox expression domain alterations induced by retinoic acid, valproic acid, and bromoxynil during murine development[J]. J Biochem Mol Toxicol.2003.17 (6):346-356
[85]G. Duester. Retinoic acid regulation of the somitogenesis clock[J]. Birth Defects Res C Embryo Today. 2007.81 (2):84-92
[86]H. Nau,R. S. Hauck,K. Ehlers. Valproic acid-induced neural tube defects in mouse and human:aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms[J]. Pharmacol Toxicol.1991.69 (5).310-321
[87]A. Basu,F. H. Wezeman. Developmental toxicity of valproic acid during embryonic chick vertebral chondrogenesis[J]. Spine (Phila Pa 1976).2000.25 (17):2158-2164
[88]G. L. Barnes,P. G. Alexander,C. W. Hsuet al. Cloning and characterization of chicken Paraxis:a regulator of paraxial mesoderm development and somite formation[J]. Dev Biol.1997.189 (1):95-111
[89]N. D. Greene,A. J. Copp. Mouse models of neural tube defects:investigating preventive mechanisms[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):31-41
[90]K. P. Xu,Y. Li,A. V. Ljubimovet al. High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing[J]. Diabetes.2009.58 (5).1077-1085
[91]A. Aberg,L. Westbonm,B.Kallen. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes[J]. Early Hum Dev.2001.61 (2):85-95
[92]S. Akazawa. Diabetic embryopathy:studies using a rat embryo culture system and an animal model[J]. Congenit Anom (Kyoto).2005.45 (3):73-79
[93]M. R. Loeken. Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):77-87
[94]M. R. Loeken. Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy[J]. Am J Med Genet C Semin Med Genet.2005.135C (1):77-87
[95]A. Ornoy. Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis on diabetic embryopathy[J]. Reprod Toxicol.2007.24 (1):31-41
[96]K. Oyama,Y. Sugimura,T. Muraseet al. Folic acid prevents congenital malformations in the offspring of diabetic mice[J].Endocr J.2009.56 (1):29-37
[97]W. S. Webster,D. Abela. The effect of hypoxia in development[J]. Birth Defects Res C Embryo Today. 2007.81 (3):215-228
[98]J. M. Yon,I. J. Baek,S. R. Leeet al. The spatio-temporal expression pattern of cytoplasmic Cu/Zn superoxide dismutase (SOD1) mRNA during mouse embryogenesis[J]. J Mol Histol.2008.39 (1) 95-103
[99]R. Dumollard,M. Duchen,J. Carroll. The role of mitochondrial function in the oocyte and embryo[J]. Curr Top Dev Biol.2007.77:21-49
[100]J. Singh. Interaction of maternal protein and carbon monoxide on pup mortality in mice:implications for global infant mortality[J]. Birth Defects Res B Dev Reprod Toxicol.2006.77 (3):216-226
[101]M. A. Robkin. Carbon monoxide and the embryo[J]. Int J Dev Biol.1997.41 (2):283-289
[102]J. M. DeSesso,C. F. Jacobson,A. R. Scialliet al. An assessment of the developmental toxicity of inorganic arsenic[J]. Reprod Toxicol.1998.12 (4):385-433
[103]H. Thackray,C. Tifft. Fetal alcohol syndrome[J]. Pediatr Rev.2001.22 (2):47-55
[104]R. Yelin,H.Kot,D. Yelinet al. Early molecular effects of ethanol during vertebrate embryogenesis[J]. Differentiation.2007.75 (5):393-403
[105]J. G. Breen,T. W. Claggett,G. L. Kimmelet al. Heat shock during rat embryo development in vitro results in decreased mitosis and abundant cell death[J]. Reprod Toxicol.1999.13 (1):31-39
[106]JM Jr Graham,M. J. Edwards,M. J. Edwards. Teratogen update:gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans[J]. Teratology.1998.58 (5):209-221
[107]J. A. McCubrey,L. S. Steelman,R. A. Franklinet al. Targeting the RAF/MEK/ERK, PI3K/AKT and p53 pathways in hematopoietic drug resistance[J]. Adv Enzyme Regul.2007.47:64-103
[108]J. A. McCubrey,M. M. Lahair,R. A. Franklin. Reactive oxygen species-induced activation of the MAP kinase signaling pathways[J]. Antioxid Redox Signal.2006.8 (9-10):1775-1789
[109]M. C. Delfini,J. Dubrulle,P. Malapertet al. Control of the segmentation process by graded MAPK/ERK activation in the chick embryo[J]. Proc Natl Acad Sci U S A.2005.102 (32):11343-11348
[110]E. Hodges,Z. Xuan,V. Balijaet al. Genome-wide in situ exon capture for selective resequencing[J]. Nat Genet.2007.39 (12):1522-1527
[111]S. B. Ng,E.H. Turner,P.D. Robertsonet al. Targeted capture and massively parallel sequencing of 12 human exomes[J]. Nature.2009.461 (7261):272-276
[112]J. Shendure,H. Ji. Next-generation DNA sequencing[J]. Nat Biotechnol.2008.26 (10):1135-1145
[113]M. L. Metzker. Sequencing technologies-the next generation[J]. Nat Rev Genet.2010.11(1):31-46
[114]S. B. Ng,A. W. Bigham,K. J. Buckinghamet al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome[J]. Nat Genet.2010.42 (9):790-793
[115]K. Bilguvar,A. K. Ozturk,A. Louviet al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations[J]. Nature.2010.467 (7312):207-210
[116]X. J. Yao,J. Xu,Z. H. Guet al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia[J]. Nat Genet.2011.43 (4):309-315
[117]L. E. Vissers,J. de Ligt,C. Gilissenet al. A de novo paradigm for mental retardation[J]. Nat Genet. 2010.42 (12):1109-1112
[118]B. J. O'Roak,P. Deriziotis,C. Leeet al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations[J]. Nat Genet.2011.43 (6):585-589
[119]B. Xu,J. L. Roos,P. Dexheimeret al. Exome sequencing supports a de novo mutational paradigm for schizophrenia[J]. Nat Genet.2011.43 (9):864-868
[120]P. D. Stenson,M. Mort,E. V. Ballet al. The Human Gene Mutation Database:2008 update[J]. Genome Med.2009.1 (1):13
[121]G. V. Kryukov,L. A. Pennacchio,S.R.Sunyaev. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies[J]. Am J Hum Genet.2007.80 (4):727-739
[122]C. T. Chen,J. C. Wang,B.A. Cohen. The strength of selection on ultraconserved elements in the human genome[J]. Am J Hum Genet.2007.80 (4):692-704
[123]S. B. Ng,K. J. Buckingham,C. Leeet al. Exome sequencing identifies the cause of a mendelian disorder[J]. Nat Genet.2010.42 (1):30-35
[124]L. G. Biesecker. Exome sequencing makes medical genomics a reality[J]. Nat Genet.2010.42 (1) 13-14
[125]M. J. Bamshad,S. B. Ng,A. W. Bighamet al. Exome sequencing as a tool for Mendelian disease gene discovery[J]. Nat Rev Genet.2011.12 (11):745-755
[126]X. Zhang,M. Li,X. J. Zhang. [Exome sequencing and its application][J]. Yi Chuan.2011.33 (8) 847-856
[127]D. Botstein,N. Risch. Discovering genotypes underlying human phenotypes:past successes for mendelian disease, future approaches for complex disease[J]. Nat Genet.2003.33 Suppl:228-237
[128]C. T. Chen,J. C. Wang,B.A. Cohen. The strength of selection on ultraconserved elements in the human genome[J]. Am J Hum Genet.2007.80 (4):692-704
[129]M. Lynch. Rate, molecular spectrum, and consequences of human mutation[J]. Proc Natl Acad Sci U S A.2010.107 (3):961-968
[130]J. C. Roach,G. Glusman,A. F. Smitet al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing[J]. Science.2010.328 (5978).636-639
[131]J. McClellan,M. C. King. Genetic heterogeneity in human disease[J]. Cell.2010.141 (2):210-217
[132]H. Li,R. Durbin. Fast and accurate short read alignment with Burrows-Wheeler transform[J]. Bioinformatics.2009.25 (14):1754-1760
[133]I. A. Adzhubei,S. Schmidt,L. Peshkinet al. A method and server for predicting damaging missense mutations[J]. Nat Methods.2010.7(4):248-249
[134]P. C. Ng,S. Henikoff. SIFT:Predicting amino acid changes that affect protein function[J]. Nucleic Acids Res.2003.31 (13):3812-3814
[135]J. M. Schwarz,C. Rodelsperger,M. Schuelkeet al. MutationTaster evaluates disease-causing potential of sequence alterations[J]. Nat Methods.2010.7(8):575-576
[136]S. Chun,J. C. Fay. Identification of deleterious mutations within three human genomes[J]. Genome Res.2009.19 (9):1553-1561
[137]E. V. Davydov,D. L. Goode,M. Sirotaet al. Identifying a high fraction of the human genome to be under selective constraint using GERP++[J]. PLoS Comput Biol.2010.6 (12):e1001025
[138]A. Megarbane.N. Salem,E. Stephanet al. X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3[J]. Eur J Hum Genet.2000.8(9):704-708
[139]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[140]Y. Bessho,R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[141]W. Wang. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins[J]. Nat Rev Genet.2007.8 (10):735-748
[142]Y. Kee,A.D.D'Andrea. Expanded roles of the Fanconi anemia pathway in preserving genomic stability[J]. Genes Dev.2010.24 (16):1680-1694
[143]F. Vaz,H.Hanenberg,B. Schusteret al. Mutation of the RAD51C gene in a Fanconi anemia-like disorder[J]. Nat Genet. 2010.42 (5):406-409
[144]S. Unal,N. Ozbek,A. Karaet al. Five Fanconi anemia patients with unusual organ pathologies[J]. Am J Hematol.2004.77 (1):50-54
[145]S. Unal,F. Gumruk. Fanconi anemia patient with bilaterally hypoplastic scapula and unilateral winging associated with scoliosis and rib abnormality [J]. J Pediatr Hematol Oncol.2006.28 (9):616-617
[146]J. McGaughran. Klippel-Feil anomaly in Fanconi anemia[J]. Clin Dysmorphol.2003.12 (3):197
[147]R. D. Kennedy,A. D. D'Andrea. The Fanconi Anemia/BRCA pathway:new faces in the crowd[J]. Genes Dev.2005.19 (24):2925-2940
[148]A. R. Meetei,J. P. de Winter,A. L. Medhurstet al. A novel ubiquitin ligase is deficient in Fanconi anemia[J]. Nat Genet.2003.35 (2):165-170
[149]A. R. Meetei,Z. Yan,W. Wang. FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination[J]. Cell Cycle.2004.3 (2):179-181
[150]A. R. Meetei,A. L. Medhurst,C. Linget al. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M[J]. Nat Genet.2005.37 (9):958-963
[151]C. S. Tremblay,F. F. Huang,O. Habiet al. HES1 is a novel interactor of the Fanconi anemia core complex[J]. Blood.2008.112 (5):2062-2070
[152]P. Castella,S. Sawai,K. Nakaoet al. HES-1 repression of differentiation and proliferation in PC12 cells:role for the helix 3-helix 4 domain in transcription repression[J]. Mol Cell Biol.2000.20 (16) 6170-6183
[153]D. Grbavec,S. Stifani. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif[J]. Biochem Biophys Res Commun.1996.223 (3):701-705
[154]C. S. Tremblay,C. C. Huard,F. F. Huanget al. The fanconi anemia core complex acts as a transcriptional co-regulator in hairy enhancer of split 1 signaling[J]. J Biol Chem.2009.284 (20): 13384-13395
[155]S. J. Park,S. L. Ciccone,B.D. Becket al. Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins[J]. J Biol Chem.2004.279 (29):30053-30059
[156]T. Otsuki,Y. Furukawa,K. Ikedaet al. Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex[J]. Hum Mol Genet.2001.10 (23):2651-2660
[157]F. Qiao,A.Moss,G. M. Kupfer. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage-and cell cycle-regulated manner[J]. J Biol Chem.2001.276 (26):23391-23396
[158]M. Castella,R. Pujol,E. Callenet al. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations[J]. Blood.2011.117 (14):3759-3769
[159]N. B. Collins,J. B. Wilson,T. Bushet al. ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function[J]. Blood.2009.113 (10):2181-2190
[160]F. Yuan,L. Qian,X. Zhaoet al. Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms[J]. J Biol Chem.2012.287(7): 4800-4807
[161]Y. Masamizu,T. Ohtsuka,Y. Takashimaet al. Real-time imaging of the somite segmentation clock: revelation of unstable oscillators in the individual presomitic mesoderm cells[J]. Proc Natl Acad Sci U S A. 2006.103 (5):1313-1318
[162]J. K. Dale,M. Maroto. A Hesl-based oscillator in cultured cells and its potential implications for the segmentation clock[J]. Bioessays.2003.25 (3):200-203
[163]N. A. Monk. Oscillatory expression of Hesl, p53, and NF-kappaB driven by transcriptional time delays[J]. Curr Biol.2003.13 (16):1409-1413
[164]K. Takebayashi,Y. Sasai,Y. Sakaiet al. Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements[J]. J Biol Chem.1994.269 (7):5150-5156
[165]S. Agrawal,C. Archer,D. V. Schaffer. Computational models of the Notch network elucidate mechanisms of context-dependent signaling[J]. PLoS Comput Biol.2009.5(5):e1000390
[166]J. H. Baek,J. Hatakeyama,S. Sakamotoet al. Persistent and high levels of Hesl expression regulate boundary formation in the developing central nervous system[J]. Development.2006.133 (13) 2467-2476
[167JH. Shimojo,T. Ohtsuka,R. Kageyama. Oscillations in notch signaling regulate maintenance of neural progenitors[J]. Neuron.2008.58 (1):52-64
[168]M. Ishibashi.S. L. Ang,K Shiotaet al. Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects[J]. Genes Dev.1995.9 (24):3136-3148
[169]Y. Bessho,R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[170]Y. Niwa,Y. Masamizu,T. Liuet al. The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock[J]. Dev Cell.2007.13 (2):298-304
[171]J. E. Bedard,J. D. Purnell,S. M. Ware. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3[J]. Hum Mol Genet.2007.16 (2):187-198
[172]L. Zhu,G. Zhou,S. Pooleet al. Characterization of the interactions of human ZIC3 mutants with GLI3[J]. Hum Mutat.2008.29 (1):99-105
[173]S. M. Ware,K. G. Harutyunyan J. W. Belmont. Zic3 is critical for early embryonic patterning during gastrulation[J]. Dev Dyn.2006.235 (3):776-785
[174]T. Kitaguchi.T. Nagai,K. Nakataet al. Zic3 is involved in the left-right specification of the Xenopus embryo[J]. Development.2000.127 (22):4787-4795
[175]G. E. Herman,H. M. El-Hodiri. The role of ZIC3 in vertebrate development[J]. Cytogenet Genome Res.2002.99 (1-4):229-235
[176]M. J. Keller,A. B. Chitnis. Insights into the evolutionary history of the vertebrate zic3 locus from a teleost-specific zic6 gene in the zebrafish, Danio rerio[J]. Dev Genes Evol.2007.217 (7):541-547
[177]A. R. McMahon,C. S. Merzdorf. Expression of the zicl, zic2, zic3, and zic4 genes in early chick embryos[J]. BMC Res Notes.2010.3:167
[178]S. M. Ware,J. Peng,L. Zhuet al. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects[J]. Am J Hum Genet.2004.74 (1):93-105
[179]L. Zhu,J. W. Belmont,S. M. Ware. Genetics of human heterotaxias[J]. Eur J Hum Genet.2006.14 (1): 17-25
[180]G. B. Ferrero,M. Gebbia,G. Piliaet al. A submicroscopic deletion in Xq26 associated with familial situs ambiguus[J]. Am J Hum Genet.1997.61 (2):395-401
[181]R. Klootwijk,B. Franke,C. E. van der Zeeet al. A deletion encompassing Zic3 in bent tail, a mouse model for X-linked neural tube defects[J]. Hum Mol Genet.2000.9 (11):1615-1622
[182]J. B. Wallingford,R. M. Harland. Neural tube closure requires Dishevelled-dependent convergent extension of the midline[J]. Development.2002.129 (24):5815-5825
[183]B. Chung,L. G. Shaffer,S. Keatinget al. From VACTERL-H to heterotaxy:variable expressivity of ZIC3-related disorders[J]. Am J Med Genet A.2011.155A (5):1123-1128
[184]L. Ma,Tierney ES Selamet,T. Leeet al. Mutations in ZIC3 and ACVR2B are a common cause of heterotaxy and associated cardiovascular anomalies[J].Cardiol Young.2012.22 (2):194-201
[185]F. C. Wardle,V. E. Papaioannou. Teasing out T-box targets in early mesoderm[J]. Curr Opin Genet Dev.2008.18 (5):418-425
[186]L. M. Goering,K. Hoshijima,B. Huget al. An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm[J]. Proc Natl Acad Sci U S A.2003.100 (16):9410-9415
[187]D. L. Chapman,V. E. Papaioannou. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6[J]. Nature.1998.391 (6668):695-697
[188]J. Beckers,N. Schlautmann,A.Gossler. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Deltal null allele[J]. Mech Dev.2000.95 (1-2):35-46
[189]Y. Yasuhiko.S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[190]P. H. White,D. R. Farkas,E.E.McFaddenet al. Defective somite patterning in mouse embryos with reduced levels of Tbx6[J]. Development.2003.130 (8):1681-1690
[191]Y. Shen,X. Chen,L. Wanget al. Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family[J]. Am J Med Genet B Neuropsychiatr Genet.2011.156 (2):225-232
[1]M. J. McMaster,K. Ohtsuka. The natural history of congenital scoliosis. A study of two hundred and fifty-one patients[J]. J Bone Joint Surg Am.1982.64 (8):1128-1147
[2]AR Jr SHANDS,H. B. EISBERG. The incidence of scoliosis in the state of Delaware; a study of 50,000 minifilms of the chest made during a survey for tuberculosis[J]. J Bone Joint Surg Am.1955.37-A (6) 1243-1249
[3]M. J. McMaster,H.Singh. Natural history of congenital kyphosis and kyphoscoliosis. A study of one hundred and twelve patients[J]. J Bone Joint Surg Am.1999.81 (10):1367-1383
[4]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. JMed Genet. 1975.12 (3):280-288
[5]D. Jaskwhich,R. M. Ali,T. C. Patelet al. Congenital scoliosis[J]. CURRENT OPINION IN PEDIATRICS.2000.12 (1):61-66
[6]D. Hedequist,J. Emans. Congenital scoliosis:a review and update[J]. J Pediatr Orthop.2007.27 (1) 106-116
[7]A. Offiah,B. Alman,A. S. Cornieret al. Pilot assessment of a radiologic classification system for segmentation defects of the vertebrae[J]. Am J Med Genet A.2010.152A (6):1357-1371
[8]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. J Med Genet.1975.12 (3):280-288
[9]G. H. Shahcheraghi,M. H. Hobbi. Patterns and progression in congenital scoliosis[J]. J Pediatr Orthop. 1999.19 (6):766-775
[10]J. M. Connor,A. N. Conner,R. A. Connoret al. Genetic aspects of early childhood scoliosis[J]. Am J Med Genet.1987.27 (2):419-424
[11]S. B. Purkiss,B.Driscoll,W. G. Coleet al. Idiopathic scoliosis in families of children with congenital scoliosis[J]. Clin Orthop Relat Res.2002 (401):27-31
[12]R. Wynne-Davies. Congenital vertebral anomalies:aetiology and relationship to spina bifida cystica[J]. JMed Genet.1975.12 (3):280-288
[13]M. L. Martinez-Frias,E. Bermejo,L. Paisanet al. Severe spondylocostal dysostosis associated with other congenital anomalies:a clinical/epidemiologic analysis and description of ten cases from the Spanish registry[J]. Am J Med Genet.1994.51 (3):203-212
[14]D. B. Sparrow,G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[15]D. B. Sparrow,E. Guillen-Navarro,D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[16]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[17]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[18]P. Lorenz,E. Rupprecht. Spondylocostal dysostosis:dominant type[J]. Am J Med Genet.1990.35 (2): 219-221
[19]P. D. Turnpenny,R. J. Thwaites,F. N. Boulos. Evidence for variable gene expression in a large inbred kindred with autosomal recessive spondylocostal dysostosis[J]. J Med Genet.1991.28 (1):27-33
[20]S. L. Dunwoodie,D. Henrique.S. M. Harrisonet al. Mouse D113:a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo[J]. Development.1997.124 (16):3065-3076
[21]K. Kusumi,E. S. Sun,A. W. Kerrebrocket al. The mouse pudgy mutation disrupts Delta homologue D113 and initiation of early somite boundaries[J]. Nat Genet.1998.19 (3):274-278
[22]P. D. Turnpenny,B. Alman,A. S. Cornieret al. Abnormal vertebral segmentation and the notch signaling pathway in man[J]. Dev Dyn.2007.236 (6):1456-1474
[23]S. L. Dunwoodie,M. Clements,D. B. Sparrowet al. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene D113 are associated with disruption of the segmentation clock within thepresomitic mesoderm[J]. Development.2002.129 (7):1795-1806
[24]K. Kusumi,M. S. Mimoto,K. L. Covelloet al. D113 pudgy mutation differentially disrupts dynamic expression of somite genes[J]. Genesis.2004.39 (2):115-121
[25]I. B. Barrantes,A. J. Elia,K. Wunschet al. Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse[J]. Curr Biol.1999.9(9):470-480
[26]G. F. Hoyne,G. Chapman,Y. Sontaniet al. A cell autonomous role for the Notch ligand Delta-like 3 in alphabeta T-cell development[J]. Immunol Cell Biol.2011.89 (6).696-705
[27]G. Chapman,D. B. Sparrow,E. Kremmeret al. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis[J]. Hum Mol Genet.2011. 20 (5):905-916
[28]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans[J]. Am J Hum Genet.2004.74 (6):1249-1254
[29]M. Morimoto,Y. Takahashi,M. Endoet al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity[J]. Nature.2005.435 (7040):354-359
[30]M. Morimoto,N. Sasaki,M. Oginumaet al. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite[J]. Development.2007.134 (8); 1561-1569
[31]Y. Yasuhiko.S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[32]A. S. Cornier.K. Staehling-Hampton,K. M. Delventhalet al. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome[J]. Am J Hum Genet.2008.82 (6):1334-1341
[33]N. Zhang,C. R. Norton,T. Gridley. Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice[J]. Genesis.2002.33 (1):21-28
[34]K. Bruckner,L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[35]L. T. Yang,J. T. Nichols,C. Yaoet al. Fringe glycosyltransferases differentially modulate Notchl proteolysis induced by Deltal and Jaggedl [J]. Mol Biol Cell.2005.16 (2):927-942
[36]J. Chen,L. Kang,N. Zhang. Negative feedback loop formed by Lunatic fringe and Hes7 controls their oscillatory expression during somitogenesis[J]. Genesis.2005.43 (4):196-204
[37]D. B. Sparrow,D. Sillence,M. A. Wouterset al. Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis[J]. Eur J Hum Genet. 2010.18 (6):674-679
[38]Y. Floman. "Mirror image" congenital scoliosis in siblings[J]. J Spinal Disord.1991.4 (3):366-368
[39]M. K. Maisenbacher,J. S. Han,M. L. O'Brienet al. Molecular analysis of congenital scoliosis:a candidate gene approach[J]. Hum Genet.2005.116 (5):416-419
[40]N. Ghebranious,C. L. Raggio,R. D. Blanket al. Lack of evidence of WNT3A as a candidate gene for congenital vertebral malformations[J]. Scoliosis.2007.2:13
[41]P. F. Giampietro,S. L. Dunwoodie,K. Kusumiet al. Progress in the Understanding of the Genetic Etiology of Vertebral Segmentation Disorders in Humans G-2911-2010[M]. OXFORD、:BLACKWELL PUBLISHING,2009:38-67
[42]Q. Fei,Z. Wu,H. Wanget al. The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population[J]. Spine (Phila Pa 1976).2010.35 (9):983-988
[43]O. Pourquie. Vertebrate segmentation:from cyclic gene networks to scoliosis[J]. Cell.2011.145 (5): 650-663
[44]费琦,吴志宏,王以朋等LMX1A基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联[J].中国组织工程研究与临床康复,2011,15(35)：6632-6638.
[45]原所茂,吴志宏,魏斌等.HES7基因多态性与先天性脊柱侧凸的关联分析[J].中国脊柱脊髓杂志,2009,19(3)：222-226.
[46]费琦,吴志宏,王以朋等.DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究[J].中国组织工程研究与临床康复,2011,15(37)：7017-7022.
[47]费琦,吴志宏,王以朋等.中国汉族人群WNT3A基因多态性与先天性脊柱侧凸遗传易感性的关系[J].中华医学杂志,2011,91(11)：746-751.
[48]费琦,吴志宏,原所茂等.中国汉族人群PAX1基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2008,88(37)：2597-2602.
[49]费琦,吴志宏,周熹等.中国汉族人群SIM2基因多态性与先天性脊柱侧凸遗传易感性的关联研究[J].中华医学杂志,2009,89(41)：2888-2893.
[50]J. Wallin,J. Wilting,H. Kosekiet al. The role of Pax-1 in axial skeleton development[J]. Development. 1994.120 (5):1109-1121
[51]J. M. McGaughran,A.Oates,D. Donnaiet al. Mutations in PAX1 may be associated with Klippel-Feil syndrome[J]. EUROPEAN JOURNAL OF HUMAN GENETICS.2003.11 (6):468-474
[52]P. F. Giampietro,C. L. Raggio,C. E. Reynoldset al. An analysis of PAX1 in the development of vertebral malformations[J]. Clin Genet.2005.68 (5):448-453
[53]C. Farrington-Rock,V. Kirilova,L. Dillard-Telmet al. Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome[J]. Hum Mol Genet.2008.17 (5):631-641
[54]M. B. Dobbs,S. Boehm,D. K. Grangeet al. Case report:Congenital knee dislocation in a patient with larsen syndrome and a novel filamin B mutation[J]. Clin Orthop Relat Res.2008.466 (6):1503-1509
[55]L. S. Bicknell,C. Farrington-Rock,Y. Shafeghatiet al. A molecular and clinical study of Larsen syndrome caused by mutations in FLNB[J]. J Med Genet.2007.44 (2):89-98
[56]C. Goumy,A. M. Beaufrere,A. Tchirkovet al. Larsen-like phenotype associated with partial trisomy 3p and monosomy 5p[J]. Prenat Diagn.2008.28 (2):131-134
[57]J. Lu,G. Lian,R. Lenkinskiet al. Filamin B mutations cause chondrocyte defects in skeletal development[J]. Hum Mol Genet.2007.16 (14):1661-1675
[58]M. Colombani,N. Laurent,M. Le Merreret al. A new osteochondrodysplasia with severe osteopenia, preaxial polydactyly, clefting and dysmorphic features resembling filamin-related disorders[J]. Prenat Diagn.2006.26 (12):1151-1155
[59]C. Farrington-Rock,M. H. Firestein,L. S. Bicknellet al. Mutations in two regions of FLNB result in atelosteogenesis Ⅰ and Ⅲ[J].Hum Mutat.2006.27 (7):705-710
[60]D. Krakow.S. P. Robertson,L. M. Kinget al. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis[J]. Nat Genet.2004.36 (4):405-410
[61]L. S. Bicknell,T. Morgan,L. Bonafeet al. Mutations in FLNB cause boomerang dysplasia[J]. J Med Genet.2005.42 (7):e43
[62]G. Weinmaster.C. Kintner. Modulation of Notch signaling during somitogenesis[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY.2003.19:367-395
[63]G. Chapman,D. B. Sparrow,E. Kremmeret al. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis[J]. Hum Mol Genet.2011. 20 (5):905-916
[64]G. F. Hoyne,G. Chapman,Y. Sontaniet al. A cell autonomous role for the Notch ligand Delta-like 3 in alphabeta T-cell development[J]. Immunol Cell Biol.2011.89 (6):696-705
[65]S. L. Dunwoodie,D. Henrique,S. M. Harrisonet al. Mouse D113:a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo[J]. Development.1997.124 (16):3065-3076
[66]K. Kusumi,E. S. Sun,A. W. Kerrebrocket al. The mouse pudgy mutation disrupts Delta homologue D113 and initiation of early somite boundaries[J]. Nat Genet. 1998.19 (3):274-278
[67]S. L. Dunwoodie,M. Clements,D. B. Sparrowet al. Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene D113 are associated with disruption of the segmentation clock within the presomitic mesoderm[J]. Development.2002.129 (7):1795-1806
[68]P. F. Giampietro,C. L. Raggio,R. D. Blank. Synteny-defined candidate genes for congenital and idiopathic scoliosis[J]. Am J Med Genet.1999.83 (3):164-177
[69]P. D. Turnpenny,M. P. Bulman,T. M. Fraylinget al. A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3[J]. Am J Hum Genet.1999.65 (1):175-182
[70]M. P. Bulman,K. Kusumi,T. M. Fraylinget al. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis[J]. Nat Genet.2000.24 (4):438-441
[71]R. E. Fisher,H. F. Smith,K. Kusumiet al. Mutations in the Notch Pathway Alter the Patterning of Multifidus[J]. Anat Rec (Hoboken).2011:
[72JN. V. Whittock,S. Ellard,J. Duncanet al. Pseudodominant inheritance of spondylocostal dysostosis type 1 caused by two familial delta-like 3 mutations[J]. CLINICAL GENETICS.2004.66 (1):67-72
[73]P. F. Giampietro,C. L. Raggio,C. Reynoldset al. DLL3 as a candidate gene for vertebral malformations[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A.2006.140A (22) 2447-2453
[74]K. M.Loomes,S. A. Stevens,M. L. O'Brienet al. Dll3 and Notchl genetic interactions model axial segmental and craniofacial malformations of human birth defects C-5418-2011 [J]. DEVELOPMENTAL DYNAMICS.2007.236 (10):2943-2951
[75]Y. Yasuhiko,S. Haraguchi,S. Kitajimaet al. Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression[J]. Proc Natl Acad Sci U S A.2006.103 (10):3651-3656
[76]M. Morimoto,Y. Takahashi,M. Endoet al. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity[J]. Nature.2005.435 (7040):354-359
[77]M. Morimoto,N. Sasaki,M. Oginumaet al. The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite[Jj. Development.2007.134 (8) 1561-1569
[78]N. Sasaki,M. Kiso,M. Kitagawaet al. The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis[J]. Development.2011.138 (1):55-64
[79]M. Morimoto,M. Kiso,N. Sasakiet al. Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis[J]. Dev Biol.2006.300 (2):687-698
[80]C. Rallis.S. M. Pinchin,D. Ish-Horowicz. Cell-autonomous integrin control of Wnt and Notch signalling during somitogenesis[J]. Development.2010.137 (21):3591-3601
[81]M. Oginuma,Y. Takahashi,S. Kitajimaet al. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite[J]. Development.2010. 137 (9):1515-1522
[82]Y. Saga,N. Hata,H. Kosekiet al. Mesp2:a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation[J]. Genes Dev.1997.11 (14):1827-1839
[83]N. V. Whittock,D. B. Sparrow,M. A. Wouterset al. Mutated MESP2 causes spondylocostal dysostosis in humans B-3994-2008 F-4310-2010[J]. AMERICAN JOURNAL OF HUMAN GENETICS.2004.74 (6):1249-1254
[84]A. S. Cornier,K. Staehling-Hampton,K. M. Delventhalet al. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome[J]. Am J Hum Genet.2008.82 (6):1334-1341
[85]E. Goshu,H. Jin,R. Fasnachtet al. Sim2 mutants have developmental defects not overlapping with those of Siml mutants[J]. Mol Cell Biol.2002.22 (12):4147-4157
[86]Q. Fei,Z. H. Wu,X. Zhouet al. [Association study of SIM2 gene polymorphisms with susceptibility to congenital scoliosis in a Chinese Han population][J]. Zhonghua Yi Xue Za Zhi.2009.89 (41):2888-2893
[87]R. Nusse,H. E. Varmus. Wnt genes[J]. Cell.1992.69 (7):1073-1087
[88]S. Takada,K. L. Stark,M. J. Sheaet al. Wnt-3a regulates somite and tailbud formation in the mouse embryo[J]. Genes Dev.1994.8 (2):174-189
[89]WC Jr Dunty,K. K. Biris,R. B. Chalamalasettyet al. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation[J]. Development.2008.135 (1):85-94
[90]R. B. Chalamalasetty,W. C. Dunty Jr.,K. K. Biriset al. The Wnt3a/(beta)-catenin target gene Mesogeninl controls the segmentation clock by activating a Notch signalling program[J]. Nature Communications.2011.2 (1):
[91]V. E. Papaioannou. T-box genes in development:from hydra to humans[J]. Int Rev Cytol.2001.207: 1-70
[92]D. L. Chapman,V. E. Papaioannou. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6[J]. Nature.1998.391 (6668):695-697
[93]P. H. White,D. R. Farkas,E. E. McFaddenet al. Defective somite patterning in mouse embryos with reduced levels of Tbx6[J]. Development.2003.130 (8):1681-1690
[94]J. Beckers,N. Schlautmann,A. Gossler. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Deltal null allele[J]. Mech Dev.2000.95 (1-2):35-46
[95]Y. Yasuhiko.S. Kitajima,Y. Takahashiet al. Functional importance of evolutionally conserved Tbx6 binding sites in the presomitic mesoderm-specific enhancer of Mesp2[J]. Development.2008.135 (21) 3511-3519
[96]M. Oginuma,Y. Niwa,D. L. Chapmanet al. Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis[J]. Development.2008.135 (15) 2555-2562
[97]Y. Shen,X. Chen,L. Wanget al. Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family[J]. Am J Med Genet B Neuropsychiatr Genet.2011.156 (2):225-232
[98]J. Klingensmith,Y. Yang,J. D. Axelrodet al. Conservation of dishevelled structure and function between flies and mice:isolation and characterization of Dvl2[J]. Mech Dev.1996.58 (1-2):15-26
[99]N. S. Hamblet,N. Lijam,P. Ruiz-Lozanoet al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure[J]. Development.2002.129 (24):5827-5838
[100]J. H. Millonig,K. J. Millen,M. E. Hatten. The mouse Dreher gene Lmxla controls formation of the roof plate in the vertebrate CNS[J]. Nature.2000.403 (6771):764-769
[101]V. Chizhikov,E.Steshina,R. Robertset al. Molecular definition of an allelic series of mutations disrupting the mouse Lmxla (dreher) gene[J]. Mamm Genome.2006.17 (10):1025-1032
[102]K. Bruckner,L. Perez,H. Clausenet al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions[J]. Nature.2000.406 (6794):411-415
[103]D. J. Moloney.V. M. Panin,S. H. Johnstonet al. Fringe is a glycosyltransferase that modifies Notch[J]. Nature.2000.406 (6794):369-375
[104]N. Haines,K. D. Irvine. Glycosylation regulates Notch signalling[J]. Nat Rev Mol Cell Biol.2003.4 (10):786-797
[105]N. Zhang,T. Gridley. Defects in somite formation in lunatic fringe-deficient mice[J]. Nature.1998. 394 (6691):374-377
[106]D. B. Sparrow,G. Chapman,M. A. Wouterset al. Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype[J]. Am J Hum Genet.2006.78 (1) 28-37
[107]R. L. Davis,D. L. Turner. Vertebrate hairy and Enhancer of split related proteins:transcriptional repressors regulating cellular differentiation and embryonic patterning[J]. Oncogene.2001.20 (58) 8342-8357
[108]A. Fischer,M. Gessler. Delta-Notch-and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors[J]. Nucleic Acids Res.2007.35 (14):4583-4596
[109]Y. Bessho,H. Hirata,Y. Masamizuet al. Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock[J]. Genes Dev.2003.17 (12):1451-1456
[110]Y. Bessho.R. Sakata,S. Komatsuet al. Dynamic expression and essential functions of Hes7 in somite segmentation[J]. Genes Dev.2001.15 (20):2642-2647
[111]R. Kageyama,Y. Niwa,H.Shimojoet al. Ultradian oscillations in Notch signaling regulate dynamic biological events[J]. Current Topics in Developmental Biology.2010.92 (C):311-331
[112]Y. Takashima,T. Ohtsuka,A. Gonzalezet al. Intronic delay is essential for oscillatory expression in the segmentation clock[J]. Proceedings of the National Academy of Sciences of the United States of America. 2011.108 (8):3300-3305
[113]D. B. Sparrow,E.Guillen-Navarro.D. Fatkinet al. Mutation of Hairy-and-Enhancer-of-Split-7 in humans causes spondylocostal dysostosis[J]. Hum Mol Genet.2008.17 (23):3761-3766
[114]D. B. Sparrow,D. Sillence,M. A. Wouterset al. Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis[J]. Eur J Hum Genet. 2010.18 (6):674-679
[115]Y. Xue,X. Gao,C. E. Lindsellet al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1[J]. Hum Mol Genet.1999.8 (5):723-730
[116]T. Oda,A. G. Elkahloun,B. L. Pikeet al. Mutations in the human Jaggedl gene are responsible for Alagille syndrome[J]. Nat Genet.1997.16 (3):235-242
[117]C. Glaser.S. Schulz,C. Schmidtet al. Nonrandom distribution of JAG 1 mutations in patients with alagille syndrome[J]. Medizinische Genetik.2011.23 (1):106
[118]A. Cosme,A.M. Cobo,M. Meunier-Rotivalet al. Molecular and clinical characteristics of a family with Alagille syndrome[J]. Medicina Clinica.2008.130 (1):17-19
[119]C. Lertudomphonwanit,S. Treepongkaruna,D. Charoenpipopet al. Phenotypes and genotypes of alagille syndrome in thai children:Report of 4 cases[J]. Hepatology International.2011.5(1):394
[120]R. McDaniell,D. M. Warthen,P. A. Sanchez-Laraet al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway[J]. Am J Hum Genet.2006.79 (1):169-173
[121]C. Zweier.G. Hammersen,R. Behrenset al. Severe course of alagille syndrome associated with a novel NOTCH2 mutation[J]. Genetic Counseling.2010.21 (1):132-133
[122]C. Schmidt,D. Wandt,S. Schulzet al. NOTCH2 mutations in patients with Alagille syndrome[J]. Medizinische Genetik.2010.22 (1):122
[123]P. D. Turnpenny,S. Ellard. Alagille syndrome:pathogenesis, diagnosis and management[J]. Eur J Hum Genet.2011: