PRPS1基因打靶载体的构建及Treacher collins综合征致病基因筛查
|
摘要
耳聋是导致言语交流障碍的常见疾病,由遗传因素和环境因素共同引起，在所有耳聋患者中由于遗传因素导致的约占60%，主要表现为单基因遗传病。中国耳聋的发病率高、数量多、危害大，快速提高耳聋的防治水平对降低耳聋的发生率至关重要。随着我国经济发展及人民生活水平的提高，导致耳聋的各种外界环境因素的影响正在逐步减弱，遗传因素在耳聋病因学中的重要性日渐突出。近年来，随着分子遗传学研究高速发展，我们对于听觉功能和耳聋病因的理解越来越深入，一部分研究成果已应用于临床实践。但仍有许多致聋基因的功能及发病机制还不明确，深入地研究遗传性耳聋的病因和发病机理，寻找能够预测、减少后代耳聋再发风险的预防措施及新的耳聋治疗方法，对于降低耳聋的发生率、提高我国人口素质有重要的现实和长远意义。本工作针对遗传性耳聋进行了病因及发病机理的研究，分为两部分。
一、PRPS1基因打靶载体的构建及ES细胞的筛选和鉴定
本课题组在前期研究中，在国际上首次发现PRPS1基因缺陷可导致DFNX1型耳聋并初步揭示了其致聋机制，通过国际国内协作我们在英国、美国和另一中国DFNX1耳聋家系中均找到了PRPS1致病基因突变，证实了这一重要发现。通过对PRPS1致聋机制的研究，我们发现通过药物干预有可能实现DFNX1型耳聋的症状前预防（PRPS1是体内嘌呤和嘧啶核苷酸从头合成途径的重要酶类），并找到了比较理想的候选药物S-腺苷蛋氨酸（SAM），评估SAM对DFNX1型耳聋可能的疗效和安全性则需要在动物模型上进行验证。本研究利用基于ES细胞和定点同源重组原理的基因打靶技术建立DFNX1基因敲入载体，在129品系ES细胞基因组中置入与人类DFNX1突变同源的c.869T>C突变。以长短两段目的基因的同源序列构建载体，同源序列之间插入突变位点和loxP序列锚定的正选择筛选的neo基因。载体构建成功后，将线性化的载体DNA电转至ES细胞，通过同源重组技术整合到ES细胞基因组序列，利用抗生素G418和长片段PCR联合筛选的方法，剔除未发生整合和随机插入载体序列的ES细胞，并进行阳性ES细胞的筛选。该载体的构建，为DFNX1小鼠模型的建立、PRPS1基因功能研究、致聋机制、发病前预防、药物筛选等关于该疾病的后续研究工作奠定了基础。
二、 Treacher Collins综合征致病基因筛查
Treacher Collins综合征（Treacher Collins syndrome, TCS）又称为Franceschetti综合征、Franceschetti-Zwahlen-Klein综合征，是一种影响面部发育的常染色体显性遗传性疾病，因此也称为下颌面骨发育不全（Mandibulofacial Dysostosis,MFD），其主要临床表现为颅面骨发育不全包括颧骨和下颌发育不良、小耳畸形、外耳道闭锁、睑裂外下垂或巨口等，患者有特征性的鱼脸样面容。本研究对一例TCS疑似病例进行了TCOF1基因的直接测序，发现该患者携带TCOF1的第11外显子c.1639delAG杂合突变，此突变提前产生了终止密码子(p.S547X)，对其父亲、母亲进行该基因位点突变筛查，未发现同样突变，提示患儿TCOF1的第11外显子c.1639delAG杂合突变为一新生突变。本实验研究结果为该家系下一步实施的遗传咨询和产前诊断提供了资料和依据。同时对了解TCS发病机理及该病致病基因分子机制提供了新的认识。
Deafness is common disease led to obstacles of communication, caused by geneticand environmental factors.60%of deafness patients are are hereditary,which ismainly a monogenic genetic disease. In china, with the rapid development ofeconomy and the improvement of our living standards, the effects of environmentalfactors to deafness are decreased gradually.The importance of genetic factors in thecause of deafness is increasingly prominent. In recent years, with the rapiddevelopment of molecular genetics, our understanding of the auditory function andhearing loss causes is getting more and more in-depth. Some important researchfindings have been applied in clinical practice for genetic diagnosis of deafness. Butsome gene functions and mechanism lead to deafness still remain unclear. Morein-depth research on the etiology and pathogenesis of hereditary deafness is needed tolook for a forecast, reducing the risk of offspring deafness and new treatment methods,and improving the quality of our population, which has important practical andlong-term significance. In this study, the etiology and pathogenesis of hereditarydeafness were studied, which is divided into two parts:
PART1: Construction of targeting vector for knockin of PRPS1.
In the previous study, our group has reported a novel gene, PRPS1, underlyinghuman DFNX1deafness, and has deciphered its mechanism. By collaborating withseveral international groups, we have identified different PRPS1mutations in otherDFNX1families, which proved our finding. From the functional study of DFNX1mechanism, we found that using SAM has the potential to prevent DFNX1presymptomly (PRPS1is a key enzyme in pathway of purine and pyrimidinesynthesis). A mouse model mimicking human DFNX1deafness is needed to test thevalidity and security of SAM in DFNX1prevention in human. In this study, we haveestablished a gene vector for knockin of PRPS1by Gene targeting technology.Targeting ES cells from129strain mice by electro-transformation. The targeted EScells were screened out by antibiotic G418and PCR reaction. This vector provides abasis for establishment of DFNX1mouse model, PRPS1gene function research, prevention before onset, and therapeutic approaches.
PART2: Mutational screening of TCOF1gene in patients with TreacherCollins syndrome
Treacher Collins syndrome (Treacher Collins syndrome, TCS) is also known asFranceschetti syndrome, Franceschetti-Zwahlen-Klein Syndrome, is an autosomaldominant disease affecting the facial development, also known as the mandibularbone hypoplasia (Mandibulofacial Dysostosis, MFD),The typical physical featuresinclude downward slanting eyes, micrognathia, underdevelopedzygoma, conductivehearing loss, drooping part of the lateral lower eyelids, and malformed or absent ears.We have collected one sporadic patients with conductive hearing loss and notching ofthe lower eyelid recruited from Outpatient Department of our hospital. By directsequencing TCOF1, we identified a novel missense mutation c.1639delAG in the11thexon of TCOF1gene in patient, this mutation have a termination codon (p.S547X),but was not found in the gene in his parents. Results of this study can be used toconduct prenatal diagnosis in this family.
一、PRPS1基因打靶载体的构建及ES细胞的筛选和鉴定
本课题组在前期研究中，在国际上首次发现PRPS1基因缺陷可导致DFNX1型耳聋并初步揭示了其致聋机制，通过国际国内协作我们在英国、美国和另一中国DFNX1耳聋家系中均找到了PRPS1致病基因突变，证实了这一重要发现。通过对PRPS1致聋机制的研究，我们发现通过药物干预有可能实现DFNX1型耳聋的症状前预防（PRPS1是体内嘌呤和嘧啶核苷酸从头合成途径的重要酶类），并找到了比较理想的候选药物S-腺苷蛋氨酸（SAM），评估SAM对DFNX1型耳聋可能的疗效和安全性则需要在动物模型上进行验证。本研究利用基于ES细胞和定点同源重组原理的基因打靶技术建立DFNX1基因敲入载体，在129品系ES细胞基因组中置入与人类DFNX1突变同源的c.869T>C突变。以长短两段目的基因的同源序列构建载体，同源序列之间插入突变位点和loxP序列锚定的正选择筛选的neo基因。载体构建成功后，将线性化的载体DNA电转至ES细胞，通过同源重组技术整合到ES细胞基因组序列，利用抗生素G418和长片段PCR联合筛选的方法，剔除未发生整合和随机插入载体序列的ES细胞，并进行阳性ES细胞的筛选。该载体的构建，为DFNX1小鼠模型的建立、PRPS1基因功能研究、致聋机制、发病前预防、药物筛选等关于该疾病的后续研究工作奠定了基础。
二、 Treacher Collins综合征致病基因筛查
Treacher Collins综合征（Treacher Collins syndrome, TCS）又称为Franceschetti综合征、Franceschetti-Zwahlen-Klein综合征，是一种影响面部发育的常染色体显性遗传性疾病，因此也称为下颌面骨发育不全（Mandibulofacial Dysostosis,MFD），其主要临床表现为颅面骨发育不全包括颧骨和下颌发育不良、小耳畸形、外耳道闭锁、睑裂外下垂或巨口等，患者有特征性的鱼脸样面容。本研究对一例TCS疑似病例进行了TCOF1基因的直接测序，发现该患者携带TCOF1的第11外显子c.1639delAG杂合突变，此突变提前产生了终止密码子(p.S547X)，对其父亲、母亲进行该基因位点突变筛查，未发现同样突变，提示患儿TCOF1的第11外显子c.1639delAG杂合突变为一新生突变。本实验研究结果为该家系下一步实施的遗传咨询和产前诊断提供了资料和依据。同时对了解TCS发病机理及该病致病基因分子机制提供了新的认识。
Deafness is common disease led to obstacles of communication, caused by geneticand environmental factors.60%of deafness patients are are hereditary,which ismainly a monogenic genetic disease. In china, with the rapid development ofeconomy and the improvement of our living standards, the effects of environmentalfactors to deafness are decreased gradually.The importance of genetic factors in thecause of deafness is increasingly prominent. In recent years, with the rapiddevelopment of molecular genetics, our understanding of the auditory function andhearing loss causes is getting more and more in-depth. Some important researchfindings have been applied in clinical practice for genetic diagnosis of deafness. Butsome gene functions and mechanism lead to deafness still remain unclear. Morein-depth research on the etiology and pathogenesis of hereditary deafness is needed tolook for a forecast, reducing the risk of offspring deafness and new treatment methods,and improving the quality of our population, which has important practical andlong-term significance. In this study, the etiology and pathogenesis of hereditarydeafness were studied, which is divided into two parts:
PART1: Construction of targeting vector for knockin of PRPS1.
In the previous study, our group has reported a novel gene, PRPS1, underlyinghuman DFNX1deafness, and has deciphered its mechanism. By collaborating withseveral international groups, we have identified different PRPS1mutations in otherDFNX1families, which proved our finding. From the functional study of DFNX1mechanism, we found that using SAM has the potential to prevent DFNX1presymptomly (PRPS1is a key enzyme in pathway of purine and pyrimidinesynthesis). A mouse model mimicking human DFNX1deafness is needed to test thevalidity and security of SAM in DFNX1prevention in human. In this study, we haveestablished a gene vector for knockin of PRPS1by Gene targeting technology.Targeting ES cells from129strain mice by electro-transformation. The targeted EScells were screened out by antibiotic G418and PCR reaction. This vector provides abasis for establishment of DFNX1mouse model, PRPS1gene function research, prevention before onset, and therapeutic approaches.
PART2: Mutational screening of TCOF1gene in patients with TreacherCollins syndrome
Treacher Collins syndrome (Treacher Collins syndrome, TCS) is also known asFranceschetti syndrome, Franceschetti-Zwahlen-Klein Syndrome, is an autosomaldominant disease affecting the facial development, also known as the mandibularbone hypoplasia (Mandibulofacial Dysostosis, MFD),The typical physical featuresinclude downward slanting eyes, micrognathia, underdevelopedzygoma, conductivehearing loss, drooping part of the lateral lower eyelids, and malformed or absent ears.We have collected one sporadic patients with conductive hearing loss and notching ofthe lower eyelid recruited from Outpatient Department of our hospital. By directsequencing TCOF1, we identified a novel missense mutation c.1639delAG in the11thexon of TCOF1gene in patient, this mutation have a termination codon (p.S547X),but was not found in the gene in his parents. Results of this study can be used toconduct prenatal diagnosis in this family.
引文
[1] Becker M. A. Phosphoribosylpyrophosphate synthetase and the regulation ofphosphoribosylpyrophosphate production in human cells [J]. Prog Nucleic Acid ResMol Biol,2001,69(115-48.
[2] Roessler B. J., Nosal J. M., Smith P. R., et al. Human X-linkedphosphoribosylpyrophosphate synthetase superactivity is associated with distinctpoint mutations in the PRPS1gene [J]. J Biol Chem,1993,268(35):26476-81.
[3] Becker M. A., Smith P. R., Taylor W., et al. The genetic and functional basis ofpurine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetasesuperactivity [J]. J Clin Invest,1995,96(5):2133-41.
[4] Kim H. J., Sohn K. M., Shy M. E., et al. Mutations in PRPS1, which encodes thephosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis,cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5)[J]. Am J Hum Genet,2007,81(3):552-8.
[5] De Brouwer A. P., Williams K. L., Duley J. A., et al. Arts syndrome is caused byloss-of-function mutations in PRPS1[J]. Am J Hum Genet,2007,81(3):507-18.
[6] Liu X., Han D., Li J., et al. Loss-of-function mutations in the PRPS1gene cause atype of nonsyndromic X-linked sensorineural deafness, DFNX1[J]. Am J Hum Genet,2010,86(1):65-71.
[7] San Filippo J., Sung P., Klein H. Mechanism of eukaryotic homologousrecombination [J]. Annu Rev Biochem,2008,77(229-57.
[8] De Kok Y. J., Van Der Maarel S. M., Bitner-Glindzicz M., et al. Associationbetween X-linked mixed deafness and mutations in the POU domain gene POU3F4[J]. Science,1995,267(5198):685-8.
[9] Schraders M., Haas S. A., Weegerink N. J., et al. Next-generation sequencingidentifies mutations of SMPX, which encodes the small muscle protein, X-linked, as acause of progressive hearing impairment [J]. Am J Hum Genet,2011,88(5):628-34.
[10]韩冰,李建忠,程静, et al. PRPS1基因功能缺失性突变导致X-连锁非综合征性DFNX1型耳聋[J].中华耳科学杂志,01):1-8.
[11] Tyson J., Bellman S., Newton V., et al. Mapping of DFNX1to Xq22[J]. HumMol Genet,1996,5(12):2055-60.
[12] Manolis E. N., Eavey R. D., Sangwatanaroj S., et al. Hereditary postlingualsensorineural hearing loss mapping to chromosome Xq21[J]. Am J Otol,1999,20(5):621-6.
[13] Cui B., Zhang H., Lu Y., et al. Refinement of the locus for non-syndromicsensorineural deafness (DFNX1)[J]. J Genet,2004,83(1):35-8.
[14] Becker M. A., Heidler S. A., Bell G. I., et al. Cloning of cDNAs for humanphosphoribosylpyrophosphate synthetases1and2and X chromosome localization ofPRPS1and PRPS2genes [J]. Genomics,1990,8(3):555-61.
[15] Taira M., Iizasa T., Yamada K., et al. Tissue-differential expression of twodistinct genes for phosphoribosyl pyrophosphate synthetase and existence of thetestis-specific transcript [J]. Biochim Biophys Acta,1989,1007(2):203-8.
[16] Pablo García-Pavía Rosa J. Torres, Manuel Rivero, Maqbool Ahmed, JuanGarcía-Puig, Michael A. Becker. Phosphoribosylpyrophosphate synthetaseoveractivity as a cause of uric acid overproduction in a young woman [J]. Arthritis&Rheumatism,2003,2003(7):2036-41.
[17] Kim Hj Sohn Km, Shy Me, Et Al. Mutations in PRPS1, which encodes thephosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis,cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5)[J]. Am J Hum Genet,2007,81(3):552-8.
[18] De Brouwer Apm Williams Kl, Duley Ja, Et Al. Arts syndrome is caused byloss-of-function mutations in PRPS1[J]. Am J Hum Genet,2007,81(3):507-18.
[19]李建忠.遗传性非综合征型耳聋的分子机制研究[D];中国人民解放军军医进修学院.
[20] Evans M. J., Kaufman M. H. Establishment in culture of pluripotential cellsfrom mouse embryos [J]. Nature,1981,292(5819):154-6.
[21] Martin G. R. Isolation of a pluripotent cell line from early mouse embryoscultured in medium conditioned by teratocarcinoma stem cells [J]. Proc Natl Acad SciU S A,1981,78(12):7634-8.
[22] Fuchs E., Segre J. A. Stem cells: a new lease on life [J]. Cell,2000,100(1):143-55.
[23] Hamra F. K. Gene targeting: Enter the rat [J]. Nature,2010,467(7312):161-3.
[1] Dixon J., Trainor P., Dixon M. J. Treacher Collins syndrome [J]. OrthodCraniofac Res,2007,10(2):88-95.
[2] Fazen L. E., Elmore J., Nadler H. L. Mandibulo-facial dysostosis.(Treacher-Collins syndrome)[J]. Am J Dis Child,1967,113(4):405-10.
[3] Rovin S., Dachi S. F., Borenstein D. B., et al. Mandibulofacial Dysostosis, aFamilial Study of Five Generations [J]. J Pediatr,1964,65(215-21.
[4] Jones K. L., Smith D. W., Harvey M. A., et al. Older paternal age and fresh genemutation: data on additional disorders [J]. J Pediatr,1975,86(1):84-8.
[5] Trainor P. A., Dixon J., Dixon M. J. Treacher Collins syndrome: etiology,pathogenesis and prevention [J]. Eur J Hum Genet,2009,17(3):275-83.
[6] Thomson Allen. Notice of several cases of malformation of the external ear,together with experiments on the state of hearing in suh persons [J]. Monthly J MedSci,1846,7):420.
[7] Collins. E Treacher. Cases with symmetrical congenital notches in the outer partof each lid and defective development of the malar bones [J]. Trans Ophthalmol SocUK,1990,20(190-200.
[8] Dixon M. J., Dixon J., Houseal T., et al. Narrowing the position of the TreacherCollins syndrome locus to a small interval between three new microsatellite markersat5q32-33.1[J]. Am J Hum Genet,1993,52(5):907-14.
[9] Dauwerse J. G., Dixon J., Seland S., et al. Mutations in genes encoding subunitsof RNA polymerases I and III cause Treacher Collins syndrome [J]. Nat Genet,2011,43(1):20-2.
[10] Epstein Erickson and Wynshaw-Boris. In born Errors of Development [M].2ed.:permission of Oxford University Press,2008.
[11] Poswillo D. The pathogenesis of the Treacher Collins syndrome(mandibulofacial dysostosis)[J]. Br J Oral Surg,1975,13(1):1-26.
[12] Stovin J. J., Lyon J. A., Jr., Clemmens R. L. Mandibulofacial dysostosis [J].Radiology,1960,74(225-31.
[13] Kolar J. C., Farkas L. G., Munro I. R. Surface morphology in Treacher Collinssyndrome: an anthropometric study [J]. Cleft Palate J,1985,22(4):266-74.
[14] Phelps P. D., Poswillo D., Lloyd G. A. The ear deformities in mandibulofacialdysostosis (Treacher Collins syndrome)[J]. Clin Otolaryngol Allied Sci,1981,6(1):15-28.
[15] Dixon M. J., Marres H. A., Edwards S. J., et al. Treacher Collins syndrome:correlation between clinical and genetic linkage studies [J]. Clin Dysmorphol,1994,3(2):96-103.
[16] Marres H. A., Cremers C. W., Dixon M. J., et al. The Treacher Collins syndrome.A clinical, radiological, and genetic linkage study on two pedigrees [J]. ArchOtolaryngol Head Neck Surg,1995,121(5):509-14.
[17] Dixon M. J., Read A. P., Donnai D., et al. The gene for Treacher Collinssyndrome maps to the long arm of chromosome5[J]. Am J Hum Genet,1991,49(1):17-22.
[18] Pron G., Galloway C., Armstrong D., et al. Ear malformation and hearing lossin patients with Treacher Collins syndrome [J]. Cleft Palate Craniofac J,1993,30(1):97-103.
[19] Edwards S. J., Fowlie A., Cust M. P., et al. Prenatal diagnosis in TreacherCollins syndrome using combined linkage analysis and ultrasound imaging [J]. J MedGenet,1996,33(7):603-6.
[20] Chemke J., Mogilner B. M., Ben-Itzhak I., et al. Autosomal recessiveinheritance of Nager acrofacial dysostosis [J]. J Med Genet,1988,25(4):230-2.
[21] Gorlin Rj Cohen Mm, Levin Ls. Syndromes of the Head and Neck [N]. OxfordUniversity Press,1990-.
[22] Kay E. D., Kay C. N. Dysmorphogenesis of the mandible, zygoma, and middleear ossicles in hemifacial microsomia and mandibulofacial dysostosis [J]. Am J MedGenet,1989,32(1):27-31.
[23] Summitt R.L. Familial Goldenhar syndrome [J]. Birth Defects Orig Art Se,1969,5(106-9.
[24] Dixon J., Edwards S. J., Anderson I., et al. Identification of the complete codingsequence and genomic organization of the Treacher Collins syndrome gene [J].Genome Res,1997,7(3):223-34.
[25] Balestrazzi P., Baeteman M. A., Mattei M. G., et al. Franceschetti syndrome ina child with a de novo balanced translocation (5;13)(q11;p11) and significant decreaseof hexosaminidase B [J]. Hum Genet,1983,64(3):305-8.
[26] Jabs E. W., Li X., Coss C. A., et al. Mapping the Treacher Collins syndromelocus to5q31.3-q33.3[J]. Genomics,1991,11(1):193-8.
[27] Loftus S. K., Dixon J., Koprivnikar K., et al. Transcriptional map of theTreacher Collins candidate gene region [J]. Genome Res,1996,6(1):26-34.
[28] So R. B., Gonzales B., Henning D., et al. Another face of the Treacher Collinssyndrome (TCOF1) gene: identification of additional exons [J]. Gene,2004,328(49-57.
[29] Group the Treacher Collins Syndrome Collaborative. Positional cloning of agene involved in the pathogenesis of Treacher Collins syndrome. The TreacherCollins Syndrome Collaborative Group [J]. Nat Genet,1996,12(2):130-6.
[30] Sulik K. K., Johnston M. C., Smiley S. J., et al. Mandibulofacial dysostosis(Treacher Collins syndrome): a new proposal for its pathogenesis [J]. Am J MedGenet,1987,27(2):359-72.
[31] Sulik K. K., Smiley S. J., Turvey T. A., et al. Pathogenesis of cleft palate inTreacher Collins, Nager, and Miller syndromes [J]. Cleft Palate J,1989,26(3):209-16;discussion16.
[32] Wiley M. J., Cauwenbergs P., Taylor I. M. Effects of retinoic acid on thedevelopment of the facial skeleton in hamsters: early changes involving cranial neuralcrest cells [J]. Acta Anat (Basel),1983,116(2):180-92.
[33] Herring S. W., Rowlatt U. F., Pruzansky S. Anatomical abnormalities inmandibulofacial dysostosis [J]. Am J Med Genet,1979,3(3):225-9.
[34] Dixon J., Jones N. C., Sandell L. L., et al. Tcof1/Treacle is required for neuralcrest cell formation and proliferation deficiencies that cause craniofacialabnormalities [J]. Proc Natl Acad Sci U S A,2006,103(36):13403-8.
[35] Wise C. A., Chiang L. C., Paznekas W. A., et al. TCOF1gene encodes aputative nucleolar phosphoprotein that exhibits mutations in Treacher CollinsSyndrome throughout its coding region [J]. Proc Natl Acad Sci U S A,1997,94(7):3110-5.
[36] Marsh K. L., Dixon J., Dixon M. J. Mutations in the Treacher Collins syndromegene lead to mislocalization of the nucleolar protein treacle [J]. Hum Mol Genet,1998,7(11):1795-800.
[37] Winokur S. T., Shiang R. The Treacher Collins syndrome (TCOF1) geneproduct, treacle, is targeted to the nucleolus by signals in its C-terminus [J]. Hum MolGenet,1998,7(12):1947-52.
[38] Waitzman A. A., Posnick J. C., Armstrong D. C., et al. Craniofacial skeletalmeasurements based on computed tomography: Part II. Normal values and growthtrends [J]. Cleft Palate Craniofac J,1992,29(2):118-28.
[1] Eric S. Lander Lauren M. Linton, Bruce Birren, Et Al. Initial sequencing andanalysis of the human genome [J]. Nature,2001,409(860-921.
[2] J. Craig Venter Mark D. Adams, Eugene W. Myers, Et Al. The Sequence of theHuman Genome [J]. Science,2001,291(1304-51.
[3] Francis S. Collins Eric D. Green, Alan E. Guttmacher, Et Al. A vision for thefuture of genomics research [J]. Nature,2003,422(835-47.
[4] Tianjiao Chu Kimberly Bunce, W. Allen Hogge，Et Al. Statistical model forwhole genome sequencing and its application to minimally invasive diagnosis of fetalgenetic disease [J]. Bioinformatics,2009,25(10):1244-50.
[5] Melissa J. Fullwood Chia-Lin Wei, Edison T. Liu, Et Al. Next-generation DNAsequencing of paired-end tags (PET) for transcriptome and genome analyses [J].Genome Res,2009,19(521-32.
[6] Talima Pearson Richard T. Okinaka, Jeffrey T. Foster, Et Al. Phylogeneticunderstanding of clonal populations in an era of whole genome sequencing [J].Infection, Genetics and Evolution,2009,9(5):1010-9
[7] Metzker Michael L. Emerging technologies in DNA sequencing [J]. GenomeRes,2005,15(1767-76.
[8] Bennett St Barnes C, Cox a,Et Al. Toward the$1000human genome [J].Pharmacogenomics,2005,6(4):373-82.
[9] J Kling. Ultrafast DNA sequencing [J]. Nature Biotechnology,2003,21(12):1425-7.
[10] Jay Shendure Robi D. Mitra, Chris Varma, Et Al. Advanced sequencingtechnologies: methods and goals [J]. Nature Reviews Genetics2004,5(335-44.
[11] Bao S., Jiang R., Kwan W., et al. WITHDRAWN: Evaluation of next-generationsequencing software in mapping and assembly [J]. J Hum Genet,2011,
[12] Boetzer M., Henkel C. V., Jansen H. J., et al. Scaffolding pre-assembled contigsusing SSPACE [J]. Bioinformatics,2011,27(4):578-9.
[13] Kriseman J., Busick C., Szelinger S., et al. BING: biomedical informaticspipeline for Next Generation Sequencing [J]. J Biomed Inform,2009,43(3):428-34.
[14] Pushkarev D., Neff N. F., Quake S. R. Single-molecule sequencing of anindividual human genome [J]. Nat Biotechnol,2009,27(9):847-50.
[15] Branton D., Deamer D. W., Marziali A., et al. The potential and challenges ofnanopore sequencing [J]. Nat Biotechnol,2008,26(10):1146-53.
[16]王升跃.新一代高通量测序技术及其临床应用前景[J].广东医学,2010,31(3):269-72.
[17] Marcel Margulies Michael Egholm, William E. Altman, Et Al. Genomesequencing in microfabricated high-density picolitre reactors [J]. Nature,2005,437(376-80.
[18] Karl V. Voelkerding Shale A. Dames, Jacob D. Durtschi. Next-GenerationSequencing: From Basic Research to Diagnostics [J]. Clinical Chemistry,2009,55(4):641-58.
[19] Marcus Droege Brendon Hill. The Genome Sequencer FLX System—Longerreads, more applications, straight forward bioinformatics and more complete data sets[J]. Journal of Biotechnology,2008,136(1-2):3-10.
[20] Daniel Maclean Jonathan D. G. Jones, David J. Studholme. Application of'next-generation' sequencing technologies to microbial genetics [J]. Nature ReviewsMicrobiology,2009,7(287-96.
[21] Mardis Elaine R. Next-Generation DNA Sequencing Methods [J]. AnnualReview of Genomics and Human Genetics,2008,9(387-402.
[22] John H. Leamon William L. Lee, Karrie R. Tartaro, Et Al. A massively parallelPicoTiterPlate based platform for discrete picoliter-scale polymerase chain reactions[J]. Electrophoresis,2003,24(3769-77.
[23] Elahe Elahi Mostafa Ronaghi. Pyrosequencing: A Tool for DNA SequencingAnalysis [J]. Methods in Molecular Biology2004,255(211-9.
[24] Ronaghi Mostafa. Pyrosequencing Sheds Light on DNA Sequencing [J]. GenomeRes,2001,11(3-11.
[25] Sydney Brenner Maria Johnson, John Bridgham, Et Al. Gene expression analysisby massively parallel signature sequencing (MPSS) on microbead arrays [J]. NatureBiotechnology,2000,18(630-4.
[26] Meyer M., Kircher M. Illumina sequencing library preparation for highlymultiplexed target capture and sequencing [J]. Cold Spring Harb Protoc,2010,2010(6): pdb prot5448.
[27] Michael Imelfort Chris Duran, Jacqueline Batley, Et Al. Discovering geneticpolymorphisms in next-generation sequencing data [J]. Plant Biotechnology Journal,2009,7(4):312-7.
[28] Douglas R. Smith Aaron R. Quinlan, Heather E. Peckham Et Al. Rapidwhole-genome mutational profiling using next-generation sequencing technologies [J].Genome Res,2008,18(1638-42.
[29] Jay Shendure Gregory J. Porreca, Nikos B. Reppas, Et Al. Accurate MultiplexPolony Sequencing of an Evolved Bacterial Genome [J]. Science,2005,309(5741):1728-32
[30] Mardis Elaine R. The impact of next-generation sequencing technology ongenetics [J]. Trends in Genetics,2008,24(3):133-41.
[31] Matsumura Hideo, Kruger, Et Al. SuperSAGE: A Modern Platform forGenome-Wide Quantitative Transcript Profiling [J]. Current PharmaceuticalBiotechnology,2008,9(7):368-74.
[32] Ozsolak F., Platt A. R., Jones D. R., et al. Direct RNA sequencing [J]. Nature,2009,461(7265):814-8.
[33]沈树泉.单分子测序与个体医学[J].生理科学进展,2009,03):283-8.
[34] Ido Braslavsky Benedict Hebert, Emil Kartalov, Et Al. Sequence information canbe obtained from single DNA molecules [J]. PNAS,2003,100(7):3960-4.
[35] Harris T. D., Buzby P. R., Babcock H., et al. Single-molecule DNA sequencing ofa viral genome [J]. Science,2008,320(5872):106-9.
[36] Korlach J., Marks P. J., Cicero R. L., et al. Selective aluminum passivation fortargeted immobilization of single DNA polymerase molecules in zero-modewaveguide nanostructures [J]. Proc Natl Acad Sci U S A,2008,105(4):1176-81.
[37] http://hereditaryhearingloss.org/
[38] Nance W. E. The genetics of deafness [J]. Ment Retard Dev Disabil Res Rev,2003,9(2):109-19.
[39] Shearer A. E., Deluca A. P., Hildebrand M. S., et al. Comprehensive genetictesting for hereditary hearing loss using massively parallel sequencing [J]. Proc NatlAcad Sci U S A,2010,107(49):21104-9.
[40] Rehman A. U., Morell R. J., Belyantseva I. A., et al. Targeted capture andnext-generation sequencing identifies C9orf75, encoding taperin, as the mutated genein nonsyndromic deafness DFNB79[J]. Am J Hum Genet,2010,86(3):378-88.
[41] Schraders M., Haas S. A., Weegerink N. J., et al. Next-generation sequencingidentifies mutations of SMPX, which encodes the small muscle protein, X-linked, as acause of progressive hearing impairment [J]. Am J Hum Genet,2011,88(5):628-34.
[42] Mortazavi A., Williams B. A., Mccue K., et al. Mapping and quantifyingmammalian transcriptomes by RNA-Seq [J]. Nat Methods,2008,5(7):621-8.
[43] Lewis M. A., Quint E., Glazier A. M., et al. An ENU-induced mutation ofmiR-96associated with progressive hearing loss in mice [J]. Nat Genet,2009,41(5):614-8.
[44] Kuhn S., Johnson S. L., Furness D. N., et al. miR-96regulates the progression ofdifferentiation in mammalian cochlear inner and outer hair cells [J]. Proc Natl AcadSci U S A,2011,108(6):2355-60.
[45] Xu G., Fewell C., Taylor C., et al. Transcriptome and targetome analysis inMIR155expressing cells using RNA-seq [J]. Rna,2010,16(8):1610-22.
[46] Perez-Enciso M., Ferretti L. Massive parallel sequencing in animal genetics:wherefroms and wheretos [J]. Anim Genet,2010,41(6):561-9.
[47] Kreuze J. F., Perez A., Untiveros M., et al. Complete viral genome sequence anddiscovery of novel viruses by deep sequencing of small RNAs: a generic method fordiagnosis, discovery and sequencing of viruses [J]. Virology,2009,388(1):1-7.
[48] Armisen J., Gilchrist M. J., Wilczynska A., et al. Abundant and dynamicallyexpressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopustropicalis [J]. Genome Res,2009,19(10):1766-75.
[2] Roessler B. J., Nosal J. M., Smith P. R., et al. Human X-linkedphosphoribosylpyrophosphate synthetase superactivity is associated with distinctpoint mutations in the PRPS1gene [J]. J Biol Chem,1993,268(35):26476-81.
[3] Becker M. A., Smith P. R., Taylor W., et al. The genetic and functional basis ofpurine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetasesuperactivity [J]. J Clin Invest,1995,96(5):2133-41.
[4] Kim H. J., Sohn K. M., Shy M. E., et al. Mutations in PRPS1, which encodes thephosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis,cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5)[J]. Am J Hum Genet,2007,81(3):552-8.
[5] De Brouwer A. P., Williams K. L., Duley J. A., et al. Arts syndrome is caused byloss-of-function mutations in PRPS1[J]. Am J Hum Genet,2007,81(3):507-18.
[6] Liu X., Han D., Li J., et al. Loss-of-function mutations in the PRPS1gene cause atype of nonsyndromic X-linked sensorineural deafness, DFNX1[J]. Am J Hum Genet,2010,86(1):65-71.
[7] San Filippo J., Sung P., Klein H. Mechanism of eukaryotic homologousrecombination [J]. Annu Rev Biochem,2008,77(229-57.
[8] De Kok Y. J., Van Der Maarel S. M., Bitner-Glindzicz M., et al. Associationbetween X-linked mixed deafness and mutations in the POU domain gene POU3F4[J]. Science,1995,267(5198):685-8.
[9] Schraders M., Haas S. A., Weegerink N. J., et al. Next-generation sequencingidentifies mutations of SMPX, which encodes the small muscle protein, X-linked, as acause of progressive hearing impairment [J]. Am J Hum Genet,2011,88(5):628-34.
[10]韩冰,李建忠,程静, et al. PRPS1基因功能缺失性突变导致X-连锁非综合征性DFNX1型耳聋[J].中华耳科学杂志,01):1-8.
[11] Tyson J., Bellman S., Newton V., et al. Mapping of DFNX1to Xq22[J]. HumMol Genet,1996,5(12):2055-60.
[12] Manolis E. N., Eavey R. D., Sangwatanaroj S., et al. Hereditary postlingualsensorineural hearing loss mapping to chromosome Xq21[J]. Am J Otol,1999,20(5):621-6.
[13] Cui B., Zhang H., Lu Y., et al. Refinement of the locus for non-syndromicsensorineural deafness (DFNX1)[J]. J Genet,2004,83(1):35-8.
[14] Becker M. A., Heidler S. A., Bell G. I., et al. Cloning of cDNAs for humanphosphoribosylpyrophosphate synthetases1and2and X chromosome localization ofPRPS1and PRPS2genes [J]. Genomics,1990,8(3):555-61.
[15] Taira M., Iizasa T., Yamada K., et al. Tissue-differential expression of twodistinct genes for phosphoribosyl pyrophosphate synthetase and existence of thetestis-specific transcript [J]. Biochim Biophys Acta,1989,1007(2):203-8.
[16] Pablo García-Pavía Rosa J. Torres, Manuel Rivero, Maqbool Ahmed, JuanGarcía-Puig, Michael A. Becker. Phosphoribosylpyrophosphate synthetaseoveractivity as a cause of uric acid overproduction in a young woman [J]. Arthritis&Rheumatism,2003,2003(7):2036-41.
[17] Kim Hj Sohn Km, Shy Me, Et Al. Mutations in PRPS1, which encodes thephosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis,cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5)[J]. Am J Hum Genet,2007,81(3):552-8.
[18] De Brouwer Apm Williams Kl, Duley Ja, Et Al. Arts syndrome is caused byloss-of-function mutations in PRPS1[J]. Am J Hum Genet,2007,81(3):507-18.
[19]李建忠.遗传性非综合征型耳聋的分子机制研究[D];中国人民解放军军医进修学院.
[20] Evans M. J., Kaufman M. H. Establishment in culture of pluripotential cellsfrom mouse embryos [J]. Nature,1981,292(5819):154-6.
[21] Martin G. R. Isolation of a pluripotent cell line from early mouse embryoscultured in medium conditioned by teratocarcinoma stem cells [J]. Proc Natl Acad SciU S A,1981,78(12):7634-8.
[22] Fuchs E., Segre J. A. Stem cells: a new lease on life [J]. Cell,2000,100(1):143-55.
[23] Hamra F. K. Gene targeting: Enter the rat [J]. Nature,2010,467(7312):161-3.
[1] Dixon J., Trainor P., Dixon M. J. Treacher Collins syndrome [J]. OrthodCraniofac Res,2007,10(2):88-95.
[2] Fazen L. E., Elmore J., Nadler H. L. Mandibulo-facial dysostosis.(Treacher-Collins syndrome)[J]. Am J Dis Child,1967,113(4):405-10.
[3] Rovin S., Dachi S. F., Borenstein D. B., et al. Mandibulofacial Dysostosis, aFamilial Study of Five Generations [J]. J Pediatr,1964,65(215-21.
[4] Jones K. L., Smith D. W., Harvey M. A., et al. Older paternal age and fresh genemutation: data on additional disorders [J]. J Pediatr,1975,86(1):84-8.
[5] Trainor P. A., Dixon J., Dixon M. J. Treacher Collins syndrome: etiology,pathogenesis and prevention [J]. Eur J Hum Genet,2009,17(3):275-83.
[6] Thomson Allen. Notice of several cases of malformation of the external ear,together with experiments on the state of hearing in suh persons [J]. Monthly J MedSci,1846,7):420.
[7] Collins. E Treacher. Cases with symmetrical congenital notches in the outer partof each lid and defective development of the malar bones [J]. Trans Ophthalmol SocUK,1990,20(190-200.
[8] Dixon M. J., Dixon J., Houseal T., et al. Narrowing the position of the TreacherCollins syndrome locus to a small interval between three new microsatellite markersat5q32-33.1[J]. Am J Hum Genet,1993,52(5):907-14.
[9] Dauwerse J. G., Dixon J., Seland S., et al. Mutations in genes encoding subunitsof RNA polymerases I and III cause Treacher Collins syndrome [J]. Nat Genet,2011,43(1):20-2.
[10] Epstein Erickson and Wynshaw-Boris. In born Errors of Development [M].2ed.:permission of Oxford University Press,2008.
[11] Poswillo D. The pathogenesis of the Treacher Collins syndrome(mandibulofacial dysostosis)[J]. Br J Oral Surg,1975,13(1):1-26.
[12] Stovin J. J., Lyon J. A., Jr., Clemmens R. L. Mandibulofacial dysostosis [J].Radiology,1960,74(225-31.
[13] Kolar J. C., Farkas L. G., Munro I. R. Surface morphology in Treacher Collinssyndrome: an anthropometric study [J]. Cleft Palate J,1985,22(4):266-74.
[14] Phelps P. D., Poswillo D., Lloyd G. A. The ear deformities in mandibulofacialdysostosis (Treacher Collins syndrome)[J]. Clin Otolaryngol Allied Sci,1981,6(1):15-28.
[15] Dixon M. J., Marres H. A., Edwards S. J., et al. Treacher Collins syndrome:correlation between clinical and genetic linkage studies [J]. Clin Dysmorphol,1994,3(2):96-103.
[16] Marres H. A., Cremers C. W., Dixon M. J., et al. The Treacher Collins syndrome.A clinical, radiological, and genetic linkage study on two pedigrees [J]. ArchOtolaryngol Head Neck Surg,1995,121(5):509-14.
[17] Dixon M. J., Read A. P., Donnai D., et al. The gene for Treacher Collinssyndrome maps to the long arm of chromosome5[J]. Am J Hum Genet,1991,49(1):17-22.
[18] Pron G., Galloway C., Armstrong D., et al. Ear malformation and hearing lossin patients with Treacher Collins syndrome [J]. Cleft Palate Craniofac J,1993,30(1):97-103.
[19] Edwards S. J., Fowlie A., Cust M. P., et al. Prenatal diagnosis in TreacherCollins syndrome using combined linkage analysis and ultrasound imaging [J]. J MedGenet,1996,33(7):603-6.
[20] Chemke J., Mogilner B. M., Ben-Itzhak I., et al. Autosomal recessiveinheritance of Nager acrofacial dysostosis [J]. J Med Genet,1988,25(4):230-2.
[21] Gorlin Rj Cohen Mm, Levin Ls. Syndromes of the Head and Neck [N]. OxfordUniversity Press,1990-.
[22] Kay E. D., Kay C. N. Dysmorphogenesis of the mandible, zygoma, and middleear ossicles in hemifacial microsomia and mandibulofacial dysostosis [J]. Am J MedGenet,1989,32(1):27-31.
[23] Summitt R.L. Familial Goldenhar syndrome [J]. Birth Defects Orig Art Se,1969,5(106-9.
[24] Dixon J., Edwards S. J., Anderson I., et al. Identification of the complete codingsequence and genomic organization of the Treacher Collins syndrome gene [J].Genome Res,1997,7(3):223-34.
[25] Balestrazzi P., Baeteman M. A., Mattei M. G., et al. Franceschetti syndrome ina child with a de novo balanced translocation (5;13)(q11;p11) and significant decreaseof hexosaminidase B [J]. Hum Genet,1983,64(3):305-8.
[26] Jabs E. W., Li X., Coss C. A., et al. Mapping the Treacher Collins syndromelocus to5q31.3-q33.3[J]. Genomics,1991,11(1):193-8.
[27] Loftus S. K., Dixon J., Koprivnikar K., et al. Transcriptional map of theTreacher Collins candidate gene region [J]. Genome Res,1996,6(1):26-34.
[28] So R. B., Gonzales B., Henning D., et al. Another face of the Treacher Collinssyndrome (TCOF1) gene: identification of additional exons [J]. Gene,2004,328(49-57.
[29] Group the Treacher Collins Syndrome Collaborative. Positional cloning of agene involved in the pathogenesis of Treacher Collins syndrome. The TreacherCollins Syndrome Collaborative Group [J]. Nat Genet,1996,12(2):130-6.
[30] Sulik K. K., Johnston M. C., Smiley S. J., et al. Mandibulofacial dysostosis(Treacher Collins syndrome): a new proposal for its pathogenesis [J]. Am J MedGenet,1987,27(2):359-72.
[31] Sulik K. K., Smiley S. J., Turvey T. A., et al. Pathogenesis of cleft palate inTreacher Collins, Nager, and Miller syndromes [J]. Cleft Palate J,1989,26(3):209-16;discussion16.
[32] Wiley M. J., Cauwenbergs P., Taylor I. M. Effects of retinoic acid on thedevelopment of the facial skeleton in hamsters: early changes involving cranial neuralcrest cells [J]. Acta Anat (Basel),1983,116(2):180-92.
[33] Herring S. W., Rowlatt U. F., Pruzansky S. Anatomical abnormalities inmandibulofacial dysostosis [J]. Am J Med Genet,1979,3(3):225-9.
[34] Dixon J., Jones N. C., Sandell L. L., et al. Tcof1/Treacle is required for neuralcrest cell formation and proliferation deficiencies that cause craniofacialabnormalities [J]. Proc Natl Acad Sci U S A,2006,103(36):13403-8.
[35] Wise C. A., Chiang L. C., Paznekas W. A., et al. TCOF1gene encodes aputative nucleolar phosphoprotein that exhibits mutations in Treacher CollinsSyndrome throughout its coding region [J]. Proc Natl Acad Sci U S A,1997,94(7):3110-5.
[36] Marsh K. L., Dixon J., Dixon M. J. Mutations in the Treacher Collins syndromegene lead to mislocalization of the nucleolar protein treacle [J]. Hum Mol Genet,1998,7(11):1795-800.
[37] Winokur S. T., Shiang R. The Treacher Collins syndrome (TCOF1) geneproduct, treacle, is targeted to the nucleolus by signals in its C-terminus [J]. Hum MolGenet,1998,7(12):1947-52.
[38] Waitzman A. A., Posnick J. C., Armstrong D. C., et al. Craniofacial skeletalmeasurements based on computed tomography: Part II. Normal values and growthtrends [J]. Cleft Palate Craniofac J,1992,29(2):118-28.
[1] Eric S. Lander Lauren M. Linton, Bruce Birren, Et Al. Initial sequencing andanalysis of the human genome [J]. Nature,2001,409(860-921.
[2] J. Craig Venter Mark D. Adams, Eugene W. Myers, Et Al. The Sequence of theHuman Genome [J]. Science,2001,291(1304-51.
[3] Francis S. Collins Eric D. Green, Alan E. Guttmacher, Et Al. A vision for thefuture of genomics research [J]. Nature,2003,422(835-47.
[4] Tianjiao Chu Kimberly Bunce, W. Allen Hogge，Et Al. Statistical model forwhole genome sequencing and its application to minimally invasive diagnosis of fetalgenetic disease [J]. Bioinformatics,2009,25(10):1244-50.
[5] Melissa J. Fullwood Chia-Lin Wei, Edison T. Liu, Et Al. Next-generation DNAsequencing of paired-end tags (PET) for transcriptome and genome analyses [J].Genome Res,2009,19(521-32.
[6] Talima Pearson Richard T. Okinaka, Jeffrey T. Foster, Et Al. Phylogeneticunderstanding of clonal populations in an era of whole genome sequencing [J].Infection, Genetics and Evolution,2009,9(5):1010-9
[7] Metzker Michael L. Emerging technologies in DNA sequencing [J]. GenomeRes,2005,15(1767-76.
[8] Bennett St Barnes C, Cox a,Et Al. Toward the$1000human genome [J].Pharmacogenomics,2005,6(4):373-82.
[9] J Kling. Ultrafast DNA sequencing [J]. Nature Biotechnology,2003,21(12):1425-7.
[10] Jay Shendure Robi D. Mitra, Chris Varma, Et Al. Advanced sequencingtechnologies: methods and goals [J]. Nature Reviews Genetics2004,5(335-44.
[11] Bao S., Jiang R., Kwan W., et al. WITHDRAWN: Evaluation of next-generationsequencing software in mapping and assembly [J]. J Hum Genet,2011,
[12] Boetzer M., Henkel C. V., Jansen H. J., et al. Scaffolding pre-assembled contigsusing SSPACE [J]. Bioinformatics,2011,27(4):578-9.
[13] Kriseman J., Busick C., Szelinger S., et al. BING: biomedical informaticspipeline for Next Generation Sequencing [J]. J Biomed Inform,2009,43(3):428-34.
[14] Pushkarev D., Neff N. F., Quake S. R. Single-molecule sequencing of anindividual human genome [J]. Nat Biotechnol,2009,27(9):847-50.
[15] Branton D., Deamer D. W., Marziali A., et al. The potential and challenges ofnanopore sequencing [J]. Nat Biotechnol,2008,26(10):1146-53.
[16]王升跃.新一代高通量测序技术及其临床应用前景[J].广东医学,2010,31(3):269-72.
[17] Marcel Margulies Michael Egholm, William E. Altman, Et Al. Genomesequencing in microfabricated high-density picolitre reactors [J]. Nature,2005,437(376-80.
[18] Karl V. Voelkerding Shale A. Dames, Jacob D. Durtschi. Next-GenerationSequencing: From Basic Research to Diagnostics [J]. Clinical Chemistry,2009,55(4):641-58.
[19] Marcus Droege Brendon Hill. The Genome Sequencer FLX System—Longerreads, more applications, straight forward bioinformatics and more complete data sets[J]. Journal of Biotechnology,2008,136(1-2):3-10.
[20] Daniel Maclean Jonathan D. G. Jones, David J. Studholme. Application of'next-generation' sequencing technologies to microbial genetics [J]. Nature ReviewsMicrobiology,2009,7(287-96.
[21] Mardis Elaine R. Next-Generation DNA Sequencing Methods [J]. AnnualReview of Genomics and Human Genetics,2008,9(387-402.
[22] John H. Leamon William L. Lee, Karrie R. Tartaro, Et Al. A massively parallelPicoTiterPlate based platform for discrete picoliter-scale polymerase chain reactions[J]. Electrophoresis,2003,24(3769-77.
[23] Elahe Elahi Mostafa Ronaghi. Pyrosequencing: A Tool for DNA SequencingAnalysis [J]. Methods in Molecular Biology2004,255(211-9.
[24] Ronaghi Mostafa. Pyrosequencing Sheds Light on DNA Sequencing [J]. GenomeRes,2001,11(3-11.
[25] Sydney Brenner Maria Johnson, John Bridgham, Et Al. Gene expression analysisby massively parallel signature sequencing (MPSS) on microbead arrays [J]. NatureBiotechnology,2000,18(630-4.
[26] Meyer M., Kircher M. Illumina sequencing library preparation for highlymultiplexed target capture and sequencing [J]. Cold Spring Harb Protoc,2010,2010(6): pdb prot5448.
[27] Michael Imelfort Chris Duran, Jacqueline Batley, Et Al. Discovering geneticpolymorphisms in next-generation sequencing data [J]. Plant Biotechnology Journal,2009,7(4):312-7.
[28] Douglas R. Smith Aaron R. Quinlan, Heather E. Peckham Et Al. Rapidwhole-genome mutational profiling using next-generation sequencing technologies [J].Genome Res,2008,18(1638-42.
[29] Jay Shendure Gregory J. Porreca, Nikos B. Reppas, Et Al. Accurate MultiplexPolony Sequencing of an Evolved Bacterial Genome [J]. Science,2005,309(5741):1728-32
[30] Mardis Elaine R. The impact of next-generation sequencing technology ongenetics [J]. Trends in Genetics,2008,24(3):133-41.
[31] Matsumura Hideo, Kruger, Et Al. SuperSAGE: A Modern Platform forGenome-Wide Quantitative Transcript Profiling [J]. Current PharmaceuticalBiotechnology,2008,9(7):368-74.
[32] Ozsolak F., Platt A. R., Jones D. R., et al. Direct RNA sequencing [J]. Nature,2009,461(7265):814-8.
[33]沈树泉.单分子测序与个体医学[J].生理科学进展,2009,03):283-8.
[34] Ido Braslavsky Benedict Hebert, Emil Kartalov, Et Al. Sequence information canbe obtained from single DNA molecules [J]. PNAS,2003,100(7):3960-4.
[35] Harris T. D., Buzby P. R., Babcock H., et al. Single-molecule DNA sequencing ofa viral genome [J]. Science,2008,320(5872):106-9.
[36] Korlach J., Marks P. J., Cicero R. L., et al. Selective aluminum passivation fortargeted immobilization of single DNA polymerase molecules in zero-modewaveguide nanostructures [J]. Proc Natl Acad Sci U S A,2008,105(4):1176-81.
[37] http://hereditaryhearingloss.org/
[38] Nance W. E. The genetics of deafness [J]. Ment Retard Dev Disabil Res Rev,2003,9(2):109-19.
[39] Shearer A. E., Deluca A. P., Hildebrand M. S., et al. Comprehensive genetictesting for hereditary hearing loss using massively parallel sequencing [J]. Proc NatlAcad Sci U S A,2010,107(49):21104-9.
[40] Rehman A. U., Morell R. J., Belyantseva I. A., et al. Targeted capture andnext-generation sequencing identifies C9orf75, encoding taperin, as the mutated genein nonsyndromic deafness DFNB79[J]. Am J Hum Genet,2010,86(3):378-88.
[41] Schraders M., Haas S. A., Weegerink N. J., et al. Next-generation sequencingidentifies mutations of SMPX, which encodes the small muscle protein, X-linked, as acause of progressive hearing impairment [J]. Am J Hum Genet,2011,88(5):628-34.
[42] Mortazavi A., Williams B. A., Mccue K., et al. Mapping and quantifyingmammalian transcriptomes by RNA-Seq [J]. Nat Methods,2008,5(7):621-8.
[43] Lewis M. A., Quint E., Glazier A. M., et al. An ENU-induced mutation ofmiR-96associated with progressive hearing loss in mice [J]. Nat Genet,2009,41(5):614-8.
[44] Kuhn S., Johnson S. L., Furness D. N., et al. miR-96regulates the progression ofdifferentiation in mammalian cochlear inner and outer hair cells [J]. Proc Natl AcadSci U S A,2011,108(6):2355-60.
[45] Xu G., Fewell C., Taylor C., et al. Transcriptome and targetome analysis inMIR155expressing cells using RNA-seq [J]. Rna,2010,16(8):1610-22.
[46] Perez-Enciso M., Ferretti L. Massive parallel sequencing in animal genetics:wherefroms and wheretos [J]. Anim Genet,2010,41(6):561-9.
[47] Kreuze J. F., Perez A., Untiveros M., et al. Complete viral genome sequence anddiscovery of novel viruses by deep sequencing of small RNAs: a generic method fordiagnosis, discovery and sequencing of viruses [J]. Virology,2009,388(1):1-7.
[48] Armisen J., Gilchrist M. J., Wilczynska A., et al. Abundant and dynamicallyexpressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopustropicalis [J]. Genome Res,2009,19(10):1766-75.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |