线粒体A1555G突变相关非综合征耳聋大家系的分子病因学研究
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摘要
在永久性保存遗传资源的基础上,对淮阴的一个A1555G突变相关耳聋大家系成员的线粒体基因组、可能的核修饰位点或基因进行研究,以期为阐明A1555G突变致聋分子机理和揭示母系遗传非综合征耳聋的本质等提供重要的分子生物学资料。
一、在家系随访和临床医学检查的前提下,知情同意后,共收集到来自淮阴耳聋大家系的122例全血标本(包括85例母系成员、26例相关配偶对照和11例父系成员),并采用EB病毒转化法成功构建了115株永生化细胞系,有效地保存了该大家系的遗传资源;
二、共发现遗传性耳聋患者56例,且均为母系成员,表现出母系遗传的特征;耳聋患者个体间的听力损失程度和发病年龄差异较大,但均为双耳对称性、感音神经性高频听力损失,且多不伴有耳聋以外的其他病症,确认为非综合征型耳聋;根据构建的家系图谱分析,除线粒体DNA突变外,可能还有位于常染色体上的核基因以不规则显性遗传方式影响母系成员的临床表型;
三、采用聚合酶链反应-限制片断长度多态性分析(PCR-restriction fragment length polymorphism, PCR-RFLP)和测序技术,检测了核心分支家系中26名母系成员的线粒体DNA上1555位点和7445位点的碱基变化,进而对该家系2名母系成员(一例听力正常,另一例具有严重耳聋症状)的线粒体全基因组和其他24名母系成员线粒体12S rRNA基因和tRNA~(Ser(UCN))基因进行了全长测序。再次证明了A1555G突变是该家系成员致聋的分子生物学基础之一;与人类线粒体标准序列相比,发现临床表型完全不同两母系成员的线粒体基因组间无序列差异,均有31处序列变化,但只有A1555G和955-960insC为已知的可引起非综合征耳聋的突变,进一步研究发现该核心家系26例母系成员的线粒体基因组中除A1555G突变外,都同时存在有955-960 insC同质型突变,两突变共分离。另外,新发现一个线粒体DNA突变——7449insG,但该突变仅在2名母系成员中存在。推测955-960 insC突
Following establishment of immortal lymphoblastoid cell lines for the Chinese extensive family with nonsyndromic deafness in Huaiyin, Jiangsu Province, the whole mitochondrial genome and two putative nuclear modifier genes were PCR amplified and directly sequenced, and the chromosomal region around marker D8S277, a promising modifier locus on 8p23.1, was fine-mapped, in order to identify whether other variants in the mitochondrial DNA, mutation(s) in Connexion 26 and MTO1, or D8S277, would contribute to the pathophysiological pathway in this Chinese deafness family associated A1555G mutation.
I. Based on the clinical characterization, venous blood samples were obtained from 122 family members (including 85 matrilineal relatives, 11 patrilineal relatives and 26 spouse controls ) with informed consent, then 115 immortal lymphoblastoid cell lines were transformed using EB virus mediated by cyclosporin A.
II. Clinical characterization showed that 56/85 maternal relatives, in this family, experienced hearing loss, whose severity and age-onset varied distinctly. However, their hearing loss shared some common features, being bilateral, sensorineural, and symmetric. And the pattern of inheritance in this family strongly indicates that the mitochondrial DNA mutation may be the main factor of deafness in this family, and that the nuclear modifier gene(s) may have involved in the development of deafness, which is in an irregular autosomal dominant model.
III. PCR-RFLP (PCR-restriction fragment length polymorphism, PCR-RFLP) was used to screen both the nt1555 and the nt7445 of the mitochondrial DNA from 26 matrilineal members in the nuclear family; subsequently, the whole mitochondrial genomes from two matrilineal members (one with severe hearing loss, the other with normal hearing), 12S rRNA genes and tRNASer(UCN) from
一、在家系随访和临床医学检查的前提下,知情同意后,共收集到来自淮阴耳聋大家系的122例全血标本(包括85例母系成员、26例相关配偶对照和11例父系成员),并采用EB病毒转化法成功构建了115株永生化细胞系,有效地保存了该大家系的遗传资源;
二、共发现遗传性耳聋患者56例,且均为母系成员,表现出母系遗传的特征;耳聋患者个体间的听力损失程度和发病年龄差异较大,但均为双耳对称性、感音神经性高频听力损失,且多不伴有耳聋以外的其他病症,确认为非综合征型耳聋;根据构建的家系图谱分析,除线粒体DNA突变外,可能还有位于常染色体上的核基因以不规则显性遗传方式影响母系成员的临床表型;
三、采用聚合酶链反应-限制片断长度多态性分析(PCR-restriction fragment length polymorphism, PCR-RFLP)和测序技术,检测了核心分支家系中26名母系成员的线粒体DNA上1555位点和7445位点的碱基变化,进而对该家系2名母系成员(一例听力正常,另一例具有严重耳聋症状)的线粒体全基因组和其他24名母系成员线粒体12S rRNA基因和tRNA~(Ser(UCN))基因进行了全长测序。再次证明了A1555G突变是该家系成员致聋的分子生物学基础之一;与人类线粒体标准序列相比,发现临床表型完全不同两母系成员的线粒体基因组间无序列差异,均有31处序列变化,但只有A1555G和955-960insC为已知的可引起非综合征耳聋的突变,进一步研究发现该核心家系26例母系成员的线粒体基因组中除A1555G突变外,都同时存在有955-960 insC同质型突变,两突变共分离。另外,新发现一个线粒体DNA突变——7449insG,但该突变仅在2名母系成员中存在。推测955-960 insC突
Following establishment of immortal lymphoblastoid cell lines for the Chinese extensive family with nonsyndromic deafness in Huaiyin, Jiangsu Province, the whole mitochondrial genome and two putative nuclear modifier genes were PCR amplified and directly sequenced, and the chromosomal region around marker D8S277, a promising modifier locus on 8p23.1, was fine-mapped, in order to identify whether other variants in the mitochondrial DNA, mutation(s) in Connexion 26 and MTO1, or D8S277, would contribute to the pathophysiological pathway in this Chinese deafness family associated A1555G mutation.
I. Based on the clinical characterization, venous blood samples were obtained from 122 family members (including 85 matrilineal relatives, 11 patrilineal relatives and 26 spouse controls ) with informed consent, then 115 immortal lymphoblastoid cell lines were transformed using EB virus mediated by cyclosporin A.
II. Clinical characterization showed that 56/85 maternal relatives, in this family, experienced hearing loss, whose severity and age-onset varied distinctly. However, their hearing loss shared some common features, being bilateral, sensorineural, and symmetric. And the pattern of inheritance in this family strongly indicates that the mitochondrial DNA mutation may be the main factor of deafness in this family, and that the nuclear modifier gene(s) may have involved in the development of deafness, which is in an irregular autosomal dominant model.
III. PCR-RFLP (PCR-restriction fragment length polymorphism, PCR-RFLP) was used to screen both the nt1555 and the nt7445 of the mitochondrial DNA from 26 matrilineal members in the nuclear family; subsequently, the whole mitochondrial genomes from two matrilineal members (one with severe hearing loss, the other with normal hearing), 12S rRNA genes and tRNASer(UCN) from
引文
1. Morton NE. Genetic epidemiology of hearing impairment [J]. Ann N Y Acad SCi, 1991, 630:16-31.
2. Marazita ML, Ploughman LM, Rawlings B. et al. Genetic epidemiological studies of early-onset deafness in the US school-age population [J]. Am J Med Genet, 1993: 46: 486-491.
3. Nadol JB. Hearing loss [J]. N Engl J Med, 1993: 329: 1092-1102.
4. Gorlin RJ, Toriello HV, Cohen MM. Hereditary Hearing Loss and its Syndromes [M]. Oxford: Oxford University Press, 1995.
5. Reardon W. Genetic deafness [J]. J Med Genet, 1992, 29: 521-526.
6. Petit C. Genes responsible for human hereditary deafness: symphony of a thousand [J]. Nat Genet, 1996: 14: 385-391.
7. Resendes BL, Williamson RE, Morton CC. At the speed of sound: gene discovery in the auditory system [J]. Am J Hum Genet, 2001: 69: 923-935.
8. Van Camp G, Willems PJ, Smith RJH. Nonsyndromic hearing impairment: unparalleled heterogeneity [J]. Am J Hum Genet, 1997: 60: 758-764.
9. Kalatzis V, Petit C. The fundamental and medical impacts of recent progress in research on hereditary hearing loss [J]. Hum Mol Genet, 1998: 7: 1589-1597.
10. Keats BJB, Berlin CI. Genomics and hearing impairment [J]. Genome Res, 1999: 9: 7-16.
11. Robertson ND, Morton CC. Beginning of a molecular era in hearing and deafness [J]. Clin Genet, 1999,55: 149-159.
12. Willems PJ. Genetic causes of hearing loss [J]. N Engl J Med, 2000, 342: 1101-1109.
13. Steel KP, Kros CJ. A Genetic approach to understanding auditory function [J]. Nat Genet, 2001:27: 143-149.
14. Petersen MB. Non-syndromic autosomal-dominant deafness [J]. Clin Genet, 2002, 62: 1-13.
15. Friedman TB, Griffith AJ. Human nonsyndromic sensorineural deafness [J]. Annu Rev Genomica Hum Genet, 2003,4:341-402
16. Kumar NM and Gilula NB. The gap junction communication channel [J]. Cell, 1996, 84(3): 381-8.
17. Kelsell DP, Dunlop J, Stevens HP, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness [J]. Nature, 1997, 387(6628): 80-3.
18. Grifa A, Wagner CA, Dambrosio L, et al. Mutations in GJB6 cause nonsyndomic autosomal dominant deafness at DFNA3 locus [J]. Nature Genetics, 1999, 23:16-18.
19. Denoyelle F, Weil D, Maw MA, et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene [J]. Hum Mol Genet, 1997, 6(12): 2173-7.
20. Kelley PM, Harris DJ, Comer BC, et al. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss [J]. Am J Hum Genet, 1998, 62(4): 792-9.
21. Kiang, DTJin N, Tu ZJ, et al. Upstream genomic sequence of the human connexin26 gene. Gene [J]. 1997, 199: 165-171.
22. Kelley DP, Conn E, Kimberling WJ. Connexin26: required for normal auditory function [J]. Brain Res Brain Res Rev, 2000, 32:184-188.
23. Kikuchi T, Kimura RS, Paul DL, et al. Gap junction system in mammalian cochlea [J]. Brain Res Brain Res Rev, 2000, 32: 163-166.
24. Rabionet, R, Gasparini, P, Estivill, X. Molecular Genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins [J]. Hum Mutat, 2000, 16: 190-202.
25. Heathcote, K, Syrris P, Carter, ND. A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis [J]. J Med Genet, 2000, 37: 50-51.
26. Morle L, Bozon M, Alloisio N. A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss [J]. J Med Genet, 2000, 37: 368-370.
27. Pandya A, Arnos KS, Xia XJ. Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands [J]. Genet, Med, 2003, 5: 295-303.
28. Kenneson A, Van Naarden Braun K, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review [J]. Genet, Med, 2002, 4: 258-274.
29. Carrasquillo MM, Zlotogora J, Barges S, et al. Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for Genetic studies in isolated populations [J]. Hum Mol Genet, 1997, 6: 2163-2172.
30. Zelante L, Gasparini P, Estivill X, et al. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans [J]. HumMolec Genet, 1997, 6: 1605-1609.
31. Estivill X, Fortina P, Surrey S, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet, 1998, 351: 394-398.
32. Abe S, Usami S, Shinkawa H,et al. Prevalent connexin 26 gene (GJB2) mutations in Japanese [J]. J Med Genet, 2000, 37: 41-43.
33. Kudo T, Ikeda K, Kure S, et al. Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population [J]. Am J Med Genet, 2000, 90: 141-145.
34. Liu XZ, Xia XJ, Ke XM, et al. The prevalence of connexin 26 (GJB2) mutations in the Chinese population [J]. Hum Genet, 2002, 111: 394-397.
35. Yan D, Park HJ, Ouyang XM, et al. Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in east Asians [J]. Hum Genet, 2003, 114: 44-50.
36．徐悦凡，任鲁风，宋文芹，等．中国人非综合征型听力损失患者Cx26基因的突变分析[J]． 中华耳鼻咽喉科杂志，2002，37(5)：348—351．
37．柯肖枚，路远，刘玉和，等．Connexin26基因突变与国人遗传性无综合征耳聋相关性分析 [J]．中华耳鼻咽喉科杂志，2001，36：163～5．
38．肖自安，冯永，潘乾，等．非综合征型耳聋患者连接蛋白26基因突变的研究[J]．中华耳鼻 咽喉科杂志，2000，35：188～91．
39．李建瑞，陈瑛，郭皖北，等．中国人GJB2耳聋基因突变分析[J]．中华医学遗传学杂志， 2003，20(10)：441．433
40. Sobe T, Vreugde S, Shahin H, et al. The prevalence and expression of inherited connexin 26 mutations associated with nonsyndromic hearing loss in the Israeli population [J]. Hum Genet, 2000, 106: 50-57.
41. Morell RJ, Kim H J, Hood LJ, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness [J]. New Eng J Med, 1998, 339: 1500-1505.
42. Xia J, Liu C, Tang B, et al. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment [J]. Nature Genet, 1998, 20: 370-373.
43. Liu XZ, Xia XJ, Xu L, et al. Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss [J]. Hum Mol Genet, 2000, 9: 63-67.
44. Dahl E, Manthey D, Chen Y, et al. Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin [J]. J Biol Chem, 1996,271: 17903-17910.
45. Grifa A, Wagner CA, et al. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus [J]. Nature Genet, 1999, 23: 16-18.
46. Lautermann J, Frank H, Jahnke K, et al. Developmental expression patterns of connexin-26 and -30 in the rat cochlea [J]. Dev Genet, 1999, 25: 306-311.
47. Kelley PM, Abe S, Askew JW, et al. Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13ql2 [J]. Genomics, 1999, 62, 172-176.
48. Lamartine J, Essenfelder GM, Kibar Z, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter) [J]. Nature Genet, 2000, 26: 142-144.
49. Smith FJ, Morley SM, McLean, WH, et al. A novel connexin 30 mutation in Clouston syndrome [J]. J Invest Derm, 2002, 118: 530-532.
50. Coucke PJ, Van Hauwe P, Kelley PM, et al. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families [J]. Hum Mol Genet, 1999, 8: 1321-1328.
51. Kubisch C, Schroeder BC, Friedrich T. et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness [J]. Cell, 1999, 96: 437-446.
52. Kharkovets T, Hardelin JP, Safieddine S, et al. KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway [J]. Proc Nat Acad Sci, 2000,97: 4333-4338.
53. Talebizadeh Z, Kelley PM, Askew JW, et al. Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss [J]. Hum Mutat, 1999, 14: 493-501.
54. Van Camp G, Coucke PJ, Akita J, et al. A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment [J]. Hum Mutat, 2002, 20: 15-19.
55. Everett LA, Glaser B, Beck, JC, et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS) [J]. Nature Genet, 1997, 17: 411-422.
56. Borck G, Roth C, Martine U, et al. Mutations in the PDS gene in German families with Pendred's syndrome: V138F is a founder mutation [J]. J Clin Endocr Metab,2003, 88: 2916-2921.
57. Kraiem Z, Heinrich R, Sadeh O, et al. Sulfate transport is not impaired in Pendred syndrome thyrocytes [J]. J Clin Endocr Metab, 1999, 84: 2574-2576.
58. Lopez-Bigas N, Rabionet R, de Cid R. Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in Pendred syndrome [J]. Hum Mutat, 1999, 14: 520-526.
59. Park H.-J, Shaukat S, Liu, XZ. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness [J]. J Med Genet, 2003, 40: 242-248.
60. Pryor SP, Madeo AC, Reynolds JC. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and Genetic entities (Letter) [J]. J Med Genet, 2005, 42: 159-165.
61. Hattori M, Fujiyama A, Taylor TD. The DNA sequence of human chromosome 21 [J]. Nature, 2000,405:311-319.
62. Wilcox ER, Burton QL, Naz S. Mutations in the gene encoding tight junction claudin-14 cause recessive deafness DFNB29 [J]. Cell, 2001, 104: 165-172.
63. Wattenhofer M, Reymond A, Falciola V. Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions in vitro [J]. Hum Mutat, 2005, 25: 543-549.
64. Scott HS, Kudoh J, Wattenhofer M. Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness [J]. Nature Genet, 2001, 27: 59-63.
65. Masmoudi S, Antonarakis SE, Schwede T. Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with nonsyndromic autosomal recessive deafness [J]. Hum Mutat, 2001, 18: 101-108
66. Guipponi M, Vuagniaux G, Wattenhofer M. The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro [J]. Hum Mol Genet, 2002, 11: 2829-2836.
67. Lee YJ, Park D, Kim S. Y. Pathogenic mutations but not polymorphisms in congenital and childhood onset autosomal recessive deafness disrupt the proteolytic activity of TMPRSS3 [J]. J Med Genet, 2003,40: 629-631.
68. Bitner-Glindzicz M, Turnpenny P, Hoglund P. Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3 [J]. Hum Molec Genet, 4: 1467-1469, 1995.
69. deKok YJM, Cremers CWRJ, Ropers HH. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation [J]. Hum Mutat, 1997, 10: 207-211.
70. de Kok YJM, Merkx GFM, van der Maarel SM. A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene [J]. Hum Molec Genet, 1995, 4: 2145-2150.
71. de Kok YJM, van der Maarel SM, Bitner-Glindzicz M, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4 [J], Science, 1995, 267: 685-688.
72. Vahava O, Morell R, Lynch ED. Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans [J]. Science, 1998,279:1950-1954.
73. Borsani G, DeGrandi A, Ballabio A. EYA4, a novel vertebrate gene related to Drosophila eyes absent [J]. Hum Molec Genet, 1999,8:11-23.
74. Wayne S, Robertson NG, DeClau F. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus [J]. Hum Molec Genet, 2001,10: 195-200.
75. Schonberger J, Wang L, Shin JT. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss [J]. Nature Genet, 2005,37:418-422.
76. Peters LM, Anderson DW, Griffith AJ. Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28 [J]. Hum Molec Genet, 2002, 11: 2877-2885.
77. Verhoeven K, Van Laer, L, Kirschhofer K, et al. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment [J]. Nature Genet, 1998, 19: 60-62.
78. Mustapha M, Weil D, Chardenoux S, et al. An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21 [J]. Hum Molec Genet, 1999, 8: 409-412.
79. Balciuniene J, Dahl N, Borg E, et al. Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family [J]. Am J Hum Genet, 1998, 63: 786-793.
80. Naz S, Alasti F, Mowjoodi A, et al. Distinctive audiometric profile associated with DFNB21 alleles of TECTA [J]. J Med Genet, 2003,40: 360-363.
81. Lui VCH, Ng LJ, Sat EWY, Cheah KSE. The human alpha-2(XI) collagen gene (COL11A2): completion of coding information, identification of the promoter sequence, and precise localization within the major histocompatibility complex reveal overlap with the KE5 gene [J]. Genomics, 1996, 32:401-412.
82. McGuirt WT Prasad SD, Griffith AJ, Kunst HPM, et al. Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13) [J]. Nature Genet, 1999,23:413-419.
83. Melkoniemi, M, Brunner, HG, Manouvrier, S, et al. Autosomal recessive disorder otospondylomegaepiphyseal dysplasia is associated with loss-of-function mutations in the COL11A2 gene [J]. Am J Hum Genet, 2000,66: 368-377.
84. Vuoristo, MM, Pappas, JG, Jansen, V, et al. A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome [J]. Am J Med Genet, 2004, 130A: 160-164.
85. Zwaenepoel, I, Mustapha, M, Leibovici, M, et al. Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22 [J]. Proc. Nat. Acad. Sci, 2002, 99: 6240-6245.
86. Robertson NG, Lu L, Heller S, et al. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction [J]. Nature Genet, 1998, 20: 299-303.
87. Fransen, E, Verstreken, M, Verhagen, W. et al. High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene [J]. Hum Molec Genet, 1999, 8: 1425-1429.
88. Grabski R, Szul T, Sasaki T, et al. Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin [J]. Hum Genet, 2003,113:406-416.
89. Usami S, Takahashi K, Yuge I, et al. Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease [J]. Europ. J Hum Genet, 2003,11: 744-478.
90. Ahituv N, Sobe T, Robertson NG, et al. Genomic structure of the human unconventional myosin VI gene. Gene [J]. 2000,261: 269-275.
91. Melchionda S, Ahituv N, Bisceglia L, et al. MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss [J]. Am J Hum Genet, 2001, 69: 635-640.
92. Ahmed ZM, Morell RJ, Riazuddin S, et al. Mutations of MYO6 are associated with recessive deafness, DFNB37 [J]. Am J Hum Genet, 2003, 72: 1315-1322.
93. Mohiddin SA, Ahmed ZM, Griffith AJ, et al. Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MY06) (Letter) [J]. J Med Genet, 2004,41: 309-314.
94. Leal A, Endele S, Stengel C, et al. A novel myosin heavy chain gene in human chromosome 19ql3.3 [J]. Gene, 2003, 312: 165-171.
95. Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family [J]. J Biol Chem, 2004, 279;-2800-2808.
96. Donaudy F, Snoeckx R, Pfister M, et al. Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4) [J]. Am J Hum Genet, 2004, 74: 770-776.
97. Dose AC, Burnside B. Cloning and chromosomal localization of a human class III myosin [J]. Genomics, 2000, 67: 333-342.
98. Walsh T, Walsh V, Vreugde S, et al. From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30 [J]. Proc Nat Acad Sci, 2002,99:7518-7523.
99. Kelley PM, Weston MD, Chen ZY, et al. The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A) [J]. Genomics, 1997,40: 73-79.
100. Liu XZ, Walsh J, Mburu P, et al. Mutations in the myosin VILA gene cause non-syndromic recessive deafness [J]. Nature Genet, 1997,16: 188-190.
101. Weil D, Kussel P, Blanchard S, et al. The autosomal recessive isolated deafness, DFNB2, and the UsherlB syndrome are allelic defects of the myosin-VIIA gene [J]. Nature Genet, 1997, 16: 191-193.
102. Liu XZ, Walsh J, Tamagawa Y, et al. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene (Letter) [J]. Nature Genet, 1997,17: 268-269.
103. Weston MD, Kelley PM, Overbeck LD, et al. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients [J]. Am J Hum Genet, 1996, 59: 1074-1083.
104. Wang A, Liang Y, Fridell RA, et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3 [J]. Science, 1998, 280: 1447-1451.
105.Liburd N, Ghosh M, Riazuddin S, et al. Novel mutations of MYO15A associated withprofound deafness in consanguineous families and moderately severe hearing loss in a patientwith Smith-Magenis syndrome [J]. Hum Genet, 2001,109: 535-541. 106.Belyantseva LA, Boger ET, Naz S, et al. Myosin-XVa is required for tip localization ofwhirlin and differential elongation of hair-cell stereocilia [J]. Nature Cell Biol, 2005, 7:148-156.
107. Lynch ED, Lee MK, Morrow JE, et al. Nonsyndromic deafness DFNA1 associated with mutation of the human homolog of the Drosophila gene diaphanous [J]. Science, 1997, 278: 1315-1318.
108. Rose R, Weyand M, Lammers M, et al. Structural and mechanistic insights into the interaction between Rho and mammalian Dia (Letter) [J]. Nature, 2005,435: 513-518.
109.Lalwani AK, Goldstein JA, Kelley MJ, et al. Human nonsyndromic hereditary deafnessDFNA17 is due to a mutation in nonmuscle myosin MYH9 [J]. Am J Hum Genet, 2000, 67:1121-1128.
110.Martignetti JA, Heath KE, Harris J, et al. The gene for May-Hegglin anomaly localizes to aless than 1-Mb region on chromosome 22ql2.3-13.1 [J]. Am J Hum Genet, 2000, 66:1449-1454.
111.Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosinheavy chain A, in May-Hegglin anomaly [J]. Nature Genet, 2000, 26: 106-108.
112.Moxey-Mims MM, Young G, Silverman A, et al. End-stage renal disease in two pediatricpatients with Fechtner syndrome [J]. Pediat. Nephrol, 1999, 13: 782-786.
113. Siemens J, Kazmierczak P, Reynolds A, et al. The Usher syndrome proteins cadherin 23 andharmonin form a complex by means of PDZ-domain interactions [J]. Proc Nat Acad Sci, 2002,99: 14946-14951.
114.Boeda B, El-Amraoui A, Bahloul A, et al. harmonin and cadherin 23, three Usher I geneproducts that cooperate to shape the sensory hair cell bundle [J]. EMBO J, 2002, 21:6689-6699.
115.Erba HP, Eddy R, Shows T. Structure, chromosome location, and expression of the humangamma-actin gene: differential evolution, location, and expression of the cytoskeletal beta-and gamma-actin genes [J]. Molec Cell Biol, 1988,8: 1775-1789.
116.Ueyama H, Inazawa J, Nishino H, et al. FISH localization of human cytoplasmic actin genesACTB to 7p22 and ACTG1 to 17q25 and characterization of related pseudogenes [J].CytoGenet, Cell Genet, 1996, 74: 221 -224.
117.Zhu M, Yang T, Wei S, et al. Mutations in the gamma-actin gene (ACTG1) are associatedwith dominant progressive deafness (DFNA20/26) [J]. Am J Hum Genet, 2003, 73:1082-1091.
118. van Wijk E, Krieger E, Kemperman MH, et al. A mutation in the gamma actin 1 (ACTG1)gene causes autosomal dominant hearing loss (DFNA20/26) [J]. J Med Genet, 2003, 40:879-884.
119. Yasunaga S, Grati M, Cohen-Salmon M, et al. A mutation in OTOF, encoding otoferlin, aFER-1-like protein, causes DFNB9, a nonsyndromic form of deafness [J]. Nature Genet, 1999,21: 363-369.
120. Yasunaga S, Grati M, Chardenoux S, et al. OTOF encodes multiple long and short isoforms: Genetic evidence that the long ones underlie recessive deafness DFNB9 [J]. Am J Hum Genet, 2000, 67: 591-600.
121. Adato A, Raskin L, Petit C, et al. Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus [J]. Europ. J Hum Genet, 2000, 8: 437-442.
122.Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, et al. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss [J]. J Med Genet, 2002,39: 502-506.
123.Varga R, Kelley PM, Keats BJ, et al. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter) [J]. J Med Genet, 2003,40: 45-50.
124. Van Laer L, Huizing EH, Verstreken M, et al. Nonsyndromic hearing impairment is associated with a mutation in DFNA5 [J]. Nature Genetics, 1998, 20: 194-197.
125. Yu C, Meng X, Zhang S, Zhao G, et al. A 3-nucleotide deletion in the polypyrimidine tract of the intron 7 of the DFNA5 gene causes nonsyndromic hearing impairment in a Chinese family [J]. Genomics, 2003, 82: 575-579.
126. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome) [J]. Nature Genet, 1998,20: 143-148.
127.Domenech E, Gomez-Zaera M, Nunes V, et al. Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families [J]. Clin. Genet, 2004,65: 463-469.
128. Verpy E, Masmoudi S, Zwaenepoel I, et al. Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus [J]. Nature Genet, 2001, 29: 345-349.
129. Attardi G, Schatz G. Biogenesis of mitochondria [J]. Annual Review of Cell Biology. 1988,4: 289-333.
130. Wallace DC. Mitochondrial diseases in man and mouse [J]. Science, 1999,283: 1482-1488.
131.Schon EA, Bonilla E, Dimauro S. Mitochondrial ONA mutations and pathogenesis [J]. JBioenerg Biomembr. 1997,29: 131-149.
132.DiMauro S, Schon EA. Mitochondrial DNA mutations in human disease. American Journal of Medical Genetics, 2001,106(l):18 -26
133.Prezant TR, Agapian JV, Bohlman MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and nonsyndromic deafness [J]. Nat Genet, 1993, 4:289-294.
134. Guan, MX, Fishel-Ghodsian N, Attardi G. A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity [J]. Hum Mol. Genet, 2000, 9: 1787-1793.
135. Guan, MX. Molecular Pathogenetic Mechanism of Maternally Inherited Deafness [J]. Ann N YAcadSci, 2004, 259-271
136.Pandya A, Xia XJ, Erdenetungalag RM. et al. Heterogenous point mutations in the mitochondrial tRNASer(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia [J]. Am J Hum Genet, 1999, 65: 1803-1806.
137.Lopez-Bigas N, Rabionet R, Martinez E, et al. Mutations in the Mitochondrial tRNA Ser(UCN)and in the GJB2 (Connexin 26) Gene Are Not Modifiers of the Age at Onset or Severity of HearingLoss in Spanish Patients with the 12S rRNA A1555G Mutation [J]. Am J Hum Genet, 2000, 66:1465-1467
138.Torroni A, Cruciani F, Rengo C, et al. The A1555G mutation in the 12S rRNA gene of human mtDNA: Recurrent origins and founder events in families affected by sensorineural deafness [J]. Am J Hum Genet, 1999, 65:1349-1358.
139. Guan MX, Fischel-Ghodsian N, Attardi G. Biochemical evidence for nuclear gene involvementin phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation [J]. Human Molecular Genetics, 1996, 5: 963-971.
140. Guan MX, Fischel-Ghodsian N, Attardi G. Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation [J]. Hum Mol. Genet, 2001, 10: 573-580.
141.Bykhovskaya Y, Shohat M, Ehrenman K, et al. Evidence for complex nuclear inheritance in a pedigree with non-syndromic deafness due to a homoplasmic mitochondrial mutation [J].American Journal of Medical Genetics, 1998, 77:421-426.
142.Bykhovskaya Y, Yang H, Taylor K, et al. Modifier locus for mitochondrial DNA disease:Linkage and linkage disequilibrium mapping of a nuclear modifier gene for maternally inherited deafness [J]. Genetics in Medicine, 2001, 3: 177-180.
143.Bykhovskaya Y, Estivill X, Taylor K, et al. Candidate locus for a nuclear modifier gene formaternally inherited deafness [J]. Am J Hum Genet, 2000, 66:1905-1910. 144.Finnila S, Majamaa K. Lack of modulative factor in locus 8p23 in Finnish family with nonsyndromic sensorineural hearing loss associated with the 1555A>G mitochondrial DNA mutation [J]. European Journal of Human Genetics, 2003,11: 652-658.
145.Mitomap: Human Mitochondrial Genome Database. Center for Molecular Medicine Emory University, Atlanta, GA, USA World Wide Web (http://www.gen.emory.edu/mitomap.html),1995.
146.Arnaudo E, Hirano M, Seelan RS, et al. Tissue specific expression and chromosome assignment of genes specifying two isoforms of subunit Vila of human cytochrome c oxidase[J].Gene, 1992,119:299-305.
147. Bindoff LA, Howell N, Poulton J, et al. Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA [J]. J Biol Chem, 1993,268:19559-19564.
148. Fischel-Ghodsian N. Mitochondrial RNA Processing and Translation: Link between Mitochondrial Mutations and Hearing Loss [J]. Molecular Genetics and Metabolism, 1998, 65:97-104.
149. Johnson DF, Hamon, M, Fischel-Ghodsian N. Cloning and characterization of the human mitochondrial ribosomal S12 gene [J]. Genomics, 1998, 52, 363-368.
150. Bykhovskaya Y, Mengesha E, Wang D, et al. Human mitochondrial transcription factor Bl as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation [J]. Mol. Genet, Metab. 2004, 82:27-32.
151. Bykhovskaya Y, Mengesha E, Wang D, et al. Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTO1 and GTPBP3 [J]. Molecular Genetics and Metabolism, 2004, 83: 199-206.
152. Abe S, Kelley PM, Kimberling WJ, et al. Connexin 26 gene (GJB2) mutations modulates the severity of hearing loss associated with the 1555A—>G mitochondrial mutation [J]. Am J Med Genet, 2001, 103:334-338.
153. Bacino C, Prezant TR, Bu X, Fournier P, Fischel-Ghodsian N. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness [J]. Pharmaco Genetics, 1995, 5: 165-172.
154. Fischel-Ghodsian N. Mitochondrial deafness mutations reviewed [J]. Hum Mutat. 1999, 13: 261-270.
155. Li R, Greinwald JH., Yang L, et al. Molecular analysis of the mitochondrial 12S rRNA and tRNA-ser(UCN) genes in paediatric subjects with non-syndromic hearing loss [J]. Journal of Medical Genetics, 2004,41:615-620.
156.Thyagarajan D, Bressman S, Bruno C, et al. A novel mitochondrial 12SrRNA point mutation in parkinsonism, deafness, and neuropathy [J]. Ann. Neurol. 2000,48: 730-736.
157. Zhao H, Li R, Wang Q, et al. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family [J]. Am J Hum Genet, 2004, 74: 139-152.
158. Reid FM, Vernham GA, Jacobs HT. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness [J]. Hum Mutat, 1994, 3: 243-247.
159. Fischel-Ghodsian N, Prezant TR, Fournier P, et al. Mitochondrial mutation associated with nonsyndromic deafness [J]. Am J Otolaryng. 1995,16: 403-408.
160.Sevior KB, Hatamochi A, Stewart I. et al. Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness [J]. Am J Med Genet, 1998, 75: 179-185.
161.Guan MX, Enriquez JA, Fischel-Ghodsian N, et al. The deafness-associated mitochondrial DNA mutation at position 7445, which effects tRNAser(UCN) precursor processing, has long-range affects on NADH dehydrogenase subunit ND6 gene expression [J]. Molec CellBiol, 1998, 18: 5868-5879.
162.Tiranti V, Chariot P, Carella F, et al. Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNAser(UCN) gene [J]. Hum Molec Genet, 1995,4:1421-1427.
163. Verhoeven K, Ensink RJH, Tiranti V, et al. Hearing impairment and neurological dysfunction associated with a mutation in the mitochondrial tRNAser(UCN) gene [J]. Europ. J Hum Genet, 1999,7:45-51.
164.Toompuu M, Tiranti V, Zeviani M, et al. Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids [J]. Hum Molec Genet, 1999, 8: 2275-2283.
165.Hutchin TP, Parker MJ, Young ID, et al. A novel mutation in the mitochondrial tRNASer(UCN) gene in a family with non-syndromic sensorineural hearing impairment [J]. JMed Genet, 2000,37: 692-694.
166．严明．一例非综合征母系遗传耳聋大家系的分子遗传学研究[D]．博士论文
167．黄小义，刘岸，于旸，等．中国10个民族永生细胞系的建立与保存[J]．遗传，2002，24(6)，643-645．
168．乔军，刘亚琴，孙逸平，等．微量全血EB病毒转化法建立B淋巴细胞系的新技术[J]．中华实验临床免疫学杂志，1990，2：2．5．
169．李冬娜，区彩莹，陈路．建立海南黎族永生细胞库[J]。遗传，1999，21(6)：2l一22．
170．王子淑编．人体及动物细胞遗传学实验技术[M]．成都：四川大学出版社，1987．
171．周焰庚编．人类染色体[M]．北京：科学出版社，1987．
172．杨汉民著．细胞生物学实验[M]．北京：高等教育出版社2001，6．
173．卜行宽．常染色体显性遗传性感音性聋的大家系听力学调查[J]．中华耳鼻咽喉科杂志，1992，27：40．
174．郭汉璧，谭振涛，孙玉洁．显性遗传性聋大家系研究[J]．中国优生与遗传学杂志，1994， 2(2)：94—100．
175．Jaber L，Shohat M，Bu X．Sensorineural deafness inherited as a tissue specific mitochondrial disorder [J]．J Med Genet，1 992；29：86．
176．邢光前，卜行宽，严明，等．母系遗传性聋大家系听力学调查及线粒体DNA突变分析[J]． 中华耳鼻咽喉科杂志，2000，35：98—101．
177．严明，刘宁生，单祥年．一个母系遗传非综合征耳聋大家系及mtDNAl2SrRNA基因突变研究[J]．中华医学遗传学杂志，1999，5：321．325．
178.Torroni A, Rengo C, Guida V, et al. Do the four clades mtDNA haplogroupL2 evolve at different rate [J]. Am J Hum Genet, 2001, 69:1348-1356.
179. Li XM, Guan MX. A Human Mitochondrial GTP Binding Protein Related to tRNA Modification May Modulate Phenotypic Expression of the Deafness-Associated Mitochondrial 12S rRNA Mutation [J]. Mol Cell Biol, 2002, 22: 7701 - 7711.
180. Li XM, Li RH, Guan MX. Isolation and Characterization of the Putative Nuclear Modifier Gene MTOl Involved in the Pathogenesis of Deafhess-associated Mitochondrial 12 S rRNA A1555G Mutation [J]. J Biol Chem, 2002, 277: 27256 - 27264.
181. Wang YC, Kung CY, Su MC, et al. Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan [J]. Eur J Hum Genet, 2002,10:495-498
182.Bykhovskaya Y, Mengesha E, Wang D. Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTOl and GTPBP3 [J]. Mol Genet Metab, 2004, 83(3): 199-206.
1. 王宗仁,杜若甫.鹿科动物的染色体组型及其进化[J].动物学报(Wang Zong-ren, DuRuo-fu. Karyotypes of cervidae and their evolution. Acta Zoologica Sinica), 1983 , 29(3):214-221
2. 马世来,王应祥,徐龙辉. 麂属（Muntiacus ）的分类及其系统发育研究[J]. 兽类学报(Ma Shi-lai, Wang Yingxiang Taxonomic and phylogenetic studies on the genus muntiacus.Acta Theriologica Sinica), 1986, 6: 191 －207
3. SHI L M, MA C X. A new karyotype of muntjac(Muntiacus sp.) from Gongshan county in China[J]. Zoological Research, 1988, 9: 343-347
4. 王宗仁,杜若甫.1982 鹿属（Cervus ）染色体组型的进化[J]. 遗传学报(Wang Zong-ren,Du Ruo-fu. Evolution of karyotype of the genus Cervus. Acta Gentica Sinica), 1982,9(1):24-31
5. Wallace D C. Mitochondrial DNA Variation in Human Evolution, Degenerative Disease,and Aging[J]. Am. J. Hum. Genet, 1995, 57:201-223.
6. Zhang Ya-Ping, Oliver A. Ryder.Mitochondrial DNA Sequence Evolution in the Arctoidea[J]. Proc Natl Acad Sci USA, 1993, 90(20): 9557-9561.
7. Shi Yan-feng, Shan Xiang-nian Li-jian, Zhang Xiao-mei, Zhang Hai-jun. Sequencing and Organization of the Complete Mitochondrial Genome of Muntiacus muntjak[J]. Acta Zoologica Sinica, 2003, 49(5): 629-636
8. 兰宏,施立明.麂属（Muntiacus ）动物线粒体DNA 多态性及其遗传分化[J]. 中国科学（B）(Lan-Hong, Shi Li-ming. The Polymorphism and genetics differentiation of the Mitchondrial DNA of Muntiacus. Sciences in China(B) ), 1993, 23(5): 489-497
9. Avise J C. Molecular Markers, Natural History and Evolution [M]. Champman & Hall. New York. London. 1994, 511
10. Groves C P, Grubb P. Relationships of living deer [M]. In: Wemmer CM. Biology and Management of the Cervidae Washington, Smithsonia Inst Press, 1987, 21-59
11. Geist V. Endangered species and the law. Nature, 1992, 357: 274-276
12. Wang Wen, Lan Hong. Rapid and parallel chromosomal number reductions in Muntjac deer inferred from mitochondrial DNA phylogeny [J]. Mol. Biol. Evol, 2000, 17(9):1326-1333
13. Shi L M. Unique cytogenetic characteristics of a tufted deer Elaphodus cephalophus.Mamm [J]. Chromosome News1, 1981, 22: 47-51
14. Iwin D W, Kocher T D, Wilson A C. Evolution of the cytochrome b gene of mammals [J].J. Mol. Evol, 1999, 32: 128 –144
15. Irwin D M, Kocher T D, Wilson A C. Evolution of the cytochrome b gene of mammals [J]. J. Mol. Evol, 1991, 32:128-144
16. Johns G C, Avise J C. A comparative summary of genetic distances in the vertebrates from the mitochondrial cytochrome b gene [J]. Mol. Biol. Evol, 1998, 15(11):1481-1490.
17. 张亚平,Ryder O A.金丝猴属的DNA 序列变异及进化与保护遗传学研究[J].遗传学报(Zhang Ya-ping, Ryder O A. Mitochondrial DNA sequence evolution and conservation relevance of Snub-nosed Langurs Acta Gentica Sinica), 1997, 24(2): 116 －121
18. Bouvrain G., Geraads D, Jehenne Y. New data relating to the classification of the Cervidae (Artiodactyla, Mammalia) [J]. Zool. Znz, 1989, 223, 82-90
19. Ettore Randi, Nadia Mucci, Massimo Pierpaoli, Emmanuel Douzery. New phylogenetic perspectives on the Cervidae (Artiodactyla) are provided by the mitochondrial cytochrome b gene [J]. Pro. R. Soc. Lond.B,1998, 265, 793-801
20. 张亚平.从DNA 序列到物种树[J]. 动物学研究(Zhang Ya-ping. From DNA Sequence to Species Tree. Zoological Research), 1996, 17(3): 247-252
21. 张荣祖.中国自然地理－动物地理[M]. 科学出版社(Zhang Rong-zu. Physicalgeography of China- Zoo geography. Beijing: The Science Press ), 1980, 1-120
22. 易广才, 张小梅, 单祥年. 麂属(Muntiacus)动物线粒体12S RNA 细胞色素b 基因和多耐药基因序列的分析及其分子进化关系[J]. 遗传学报(Yi Guang-cai, Zhang Xiao-mei, Shan Xiang-nian. 12S rRNA Cytochrome b and MDR1 Gene DNA Sequence Phylogentic Evolution of Muntiacus [J]. Acta Gentica Sinica), 2002, 29(8): 674-680
23. 肖武汉, 张亚平. 鱼类线粒体DNA 的遗传与进化[J].水生生物学报(Xiao Wu-han,Zhang Ya-ping. Genetics and Evolution of Michondrial DNA in Fish. Acta Hydrobioloica Sinica), 2000, 24(4): 384-391
2. Marazita ML, Ploughman LM, Rawlings B. et al. Genetic epidemiological studies of early-onset deafness in the US school-age population [J]. Am J Med Genet, 1993: 46: 486-491.
3. Nadol JB. Hearing loss [J]. N Engl J Med, 1993: 329: 1092-1102.
4. Gorlin RJ, Toriello HV, Cohen MM. Hereditary Hearing Loss and its Syndromes [M]. Oxford: Oxford University Press, 1995.
5. Reardon W. Genetic deafness [J]. J Med Genet, 1992, 29: 521-526.
6. Petit C. Genes responsible for human hereditary deafness: symphony of a thousand [J]. Nat Genet, 1996: 14: 385-391.
7. Resendes BL, Williamson RE, Morton CC. At the speed of sound: gene discovery in the auditory system [J]. Am J Hum Genet, 2001: 69: 923-935.
8. Van Camp G, Willems PJ, Smith RJH. Nonsyndromic hearing impairment: unparalleled heterogeneity [J]. Am J Hum Genet, 1997: 60: 758-764.
9. Kalatzis V, Petit C. The fundamental and medical impacts of recent progress in research on hereditary hearing loss [J]. Hum Mol Genet, 1998: 7: 1589-1597.
10. Keats BJB, Berlin CI. Genomics and hearing impairment [J]. Genome Res, 1999: 9: 7-16.
11. Robertson ND, Morton CC. Beginning of a molecular era in hearing and deafness [J]. Clin Genet, 1999,55: 149-159.
12. Willems PJ. Genetic causes of hearing loss [J]. N Engl J Med, 2000, 342: 1101-1109.
13. Steel KP, Kros CJ. A Genetic approach to understanding auditory function [J]. Nat Genet, 2001:27: 143-149.
14. Petersen MB. Non-syndromic autosomal-dominant deafness [J]. Clin Genet, 2002, 62: 1-13.
15. Friedman TB, Griffith AJ. Human nonsyndromic sensorineural deafness [J]. Annu Rev Genomica Hum Genet, 2003,4:341-402
16. Kumar NM and Gilula NB. The gap junction communication channel [J]. Cell, 1996, 84(3): 381-8.
17. Kelsell DP, Dunlop J, Stevens HP, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness [J]. Nature, 1997, 387(6628): 80-3.
18. Grifa A, Wagner CA, Dambrosio L, et al. Mutations in GJB6 cause nonsyndomic autosomal dominant deafness at DFNA3 locus [J]. Nature Genetics, 1999, 23:16-18.
19. Denoyelle F, Weil D, Maw MA, et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene [J]. Hum Mol Genet, 1997, 6(12): 2173-7.
20. Kelley PM, Harris DJ, Comer BC, et al. Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss [J]. Am J Hum Genet, 1998, 62(4): 792-9.
21. Kiang, DTJin N, Tu ZJ, et al. Upstream genomic sequence of the human connexin26 gene. Gene [J]. 1997, 199: 165-171.
22. Kelley DP, Conn E, Kimberling WJ. Connexin26: required for normal auditory function [J]. Brain Res Brain Res Rev, 2000, 32:184-188.
23. Kikuchi T, Kimura RS, Paul DL, et al. Gap junction system in mammalian cochlea [J]. Brain Res Brain Res Rev, 2000, 32: 163-166.
24. Rabionet, R, Gasparini, P, Estivill, X. Molecular Genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins [J]. Hum Mutat, 2000, 16: 190-202.
25. Heathcote, K, Syrris P, Carter, ND. A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis [J]. J Med Genet, 2000, 37: 50-51.
26. Morle L, Bozon M, Alloisio N. A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss [J]. J Med Genet, 2000, 37: 368-370.
27. Pandya A, Arnos KS, Xia XJ. Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands [J]. Genet, Med, 2003, 5: 295-303.
28. Kenneson A, Van Naarden Braun K, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review [J]. Genet, Med, 2002, 4: 258-274.
29. Carrasquillo MM, Zlotogora J, Barges S, et al. Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for Genetic studies in isolated populations [J]. Hum Mol Genet, 1997, 6: 2163-2172.
30. Zelante L, Gasparini P, Estivill X, et al. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans [J]. HumMolec Genet, 1997, 6: 1605-1609.
31. Estivill X, Fortina P, Surrey S, et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet, 1998, 351: 394-398.
32. Abe S, Usami S, Shinkawa H,et al. Prevalent connexin 26 gene (GJB2) mutations in Japanese [J]. J Med Genet, 2000, 37: 41-43.
33. Kudo T, Ikeda K, Kure S, et al. Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population [J]. Am J Med Genet, 2000, 90: 141-145.
34. Liu XZ, Xia XJ, Ke XM, et al. The prevalence of connexin 26 (GJB2) mutations in the Chinese population [J]. Hum Genet, 2002, 111: 394-397.
35. Yan D, Park HJ, Ouyang XM, et al. Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in east Asians [J]. Hum Genet, 2003, 114: 44-50.
36．徐悦凡，任鲁风，宋文芹，等．中国人非综合征型听力损失患者Cx26基因的突变分析[J]． 中华耳鼻咽喉科杂志，2002，37(5)：348—351．
37．柯肖枚，路远，刘玉和，等．Connexin26基因突变与国人遗传性无综合征耳聋相关性分析 [J]．中华耳鼻咽喉科杂志，2001，36：163～5．
38．肖自安，冯永，潘乾，等．非综合征型耳聋患者连接蛋白26基因突变的研究[J]．中华耳鼻 咽喉科杂志，2000，35：188～91．
39．李建瑞，陈瑛，郭皖北，等．中国人GJB2耳聋基因突变分析[J]．中华医学遗传学杂志， 2003，20(10)：441．433
40. Sobe T, Vreugde S, Shahin H, et al. The prevalence and expression of inherited connexin 26 mutations associated with nonsyndromic hearing loss in the Israeli population [J]. Hum Genet, 2000, 106: 50-57.
41. Morell RJ, Kim H J, Hood LJ, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness [J]. New Eng J Med, 1998, 339: 1500-1505.
42. Xia J, Liu C, Tang B, et al. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment [J]. Nature Genet, 1998, 20: 370-373.
43. Liu XZ, Xia XJ, Xu L, et al. Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss [J]. Hum Mol Genet, 2000, 9: 63-67.
44. Dahl E, Manthey D, Chen Y, et al. Molecular cloning and functional expression of mouse connexin-30, a gap junction gene highly expressed in adult brain and skin [J]. J Biol Chem, 1996,271: 17903-17910.
45. Grifa A, Wagner CA, et al. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus [J]. Nature Genet, 1999, 23: 16-18.
46. Lautermann J, Frank H, Jahnke K, et al. Developmental expression patterns of connexin-26 and -30 in the rat cochlea [J]. Dev Genet, 1999, 25: 306-311.
47. Kelley PM, Abe S, Askew JW, et al. Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13ql2 [J]. Genomics, 1999, 62, 172-176.
48. Lamartine J, Essenfelder GM, Kibar Z, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. (Letter) [J]. Nature Genet, 2000, 26: 142-144.
49. Smith FJ, Morley SM, McLean, WH, et al. A novel connexin 30 mutation in Clouston syndrome [J]. J Invest Derm, 2002, 118: 530-532.
50. Coucke PJ, Van Hauwe P, Kelley PM, et al. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families [J]. Hum Mol Genet, 1999, 8: 1321-1328.
51. Kubisch C, Schroeder BC, Friedrich T. et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness [J]. Cell, 1999, 96: 437-446.
52. Kharkovets T, Hardelin JP, Safieddine S, et al. KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway [J]. Proc Nat Acad Sci, 2000,97: 4333-4338.
53. Talebizadeh Z, Kelley PM, Askew JW, et al. Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss [J]. Hum Mutat, 1999, 14: 493-501.
54. Van Camp G, Coucke PJ, Akita J, et al. A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment [J]. Hum Mutat, 2002, 20: 15-19.
55. Everett LA, Glaser B, Beck, JC, et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS) [J]. Nature Genet, 1997, 17: 411-422.
56. Borck G, Roth C, Martine U, et al. Mutations in the PDS gene in German families with Pendred's syndrome: V138F is a founder mutation [J]. J Clin Endocr Metab,2003, 88: 2916-2921.
57. Kraiem Z, Heinrich R, Sadeh O, et al. Sulfate transport is not impaired in Pendred syndrome thyrocytes [J]. J Clin Endocr Metab, 1999, 84: 2574-2576.
58. Lopez-Bigas N, Rabionet R, de Cid R. Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in Pendred syndrome [J]. Hum Mutat, 1999, 14: 520-526.
59. Park H.-J, Shaukat S, Liu, XZ. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness [J]. J Med Genet, 2003, 40: 242-248.
60. Pryor SP, Madeo AC, Reynolds JC. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and Genetic entities (Letter) [J]. J Med Genet, 2005, 42: 159-165.
61. Hattori M, Fujiyama A, Taylor TD. The DNA sequence of human chromosome 21 [J]. Nature, 2000,405:311-319.
62. Wilcox ER, Burton QL, Naz S. Mutations in the gene encoding tight junction claudin-14 cause recessive deafness DFNB29 [J]. Cell, 2001, 104: 165-172.
63. Wattenhofer M, Reymond A, Falciola V. Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions in vitro [J]. Hum Mutat, 2005, 25: 543-549.
64. Scott HS, Kudoh J, Wattenhofer M. Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness [J]. Nature Genet, 2001, 27: 59-63.
65. Masmoudi S, Antonarakis SE, Schwede T. Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with nonsyndromic autosomal recessive deafness [J]. Hum Mutat, 2001, 18: 101-108
66. Guipponi M, Vuagniaux G, Wattenhofer M. The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro [J]. Hum Mol Genet, 2002, 11: 2829-2836.
67. Lee YJ, Park D, Kim S. Y. Pathogenic mutations but not polymorphisms in congenital and childhood onset autosomal recessive deafness disrupt the proteolytic activity of TMPRSS3 [J]. J Med Genet, 2003,40: 629-631.
68. Bitner-Glindzicz M, Turnpenny P, Hoglund P. Further mutations in brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3 [J]. Hum Molec Genet, 4: 1467-1469, 1995.
69. deKok YJM, Cremers CWRJ, Ropers HH. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation [J]. Hum Mutat, 1997, 10: 207-211.
70. de Kok YJM, Merkx GFM, van der Maarel SM. A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene [J]. Hum Molec Genet, 1995, 4: 2145-2150.
71. de Kok YJM, van der Maarel SM, Bitner-Glindzicz M, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4 [J], Science, 1995, 267: 685-688.
72. Vahava O, Morell R, Lynch ED. Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans [J]. Science, 1998,279:1950-1954.
73. Borsani G, DeGrandi A, Ballabio A. EYA4, a novel vertebrate gene related to Drosophila eyes absent [J]. Hum Molec Genet, 1999,8:11-23.
74. Wayne S, Robertson NG, DeClau F. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus [J]. Hum Molec Genet, 2001,10: 195-200.
75. Schonberger J, Wang L, Shin JT. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss [J]. Nature Genet, 2005,37:418-422.
76. Peters LM, Anderson DW, Griffith AJ. Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28 [J]. Hum Molec Genet, 2002, 11: 2877-2885.
77. Verhoeven K, Van Laer, L, Kirschhofer K, et al. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment [J]. Nature Genet, 1998, 19: 60-62.
78. Mustapha M, Weil D, Chardenoux S, et al. An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21 [J]. Hum Molec Genet, 1999, 8: 409-412.
79. Balciuniene J, Dahl N, Borg E, et al. Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family [J]. Am J Hum Genet, 1998, 63: 786-793.
80. Naz S, Alasti F, Mowjoodi A, et al. Distinctive audiometric profile associated with DFNB21 alleles of TECTA [J]. J Med Genet, 2003,40: 360-363.
81. Lui VCH, Ng LJ, Sat EWY, Cheah KSE. The human alpha-2(XI) collagen gene (COL11A2): completion of coding information, identification of the promoter sequence, and precise localization within the major histocompatibility complex reveal overlap with the KE5 gene [J]. Genomics, 1996, 32:401-412.
82. McGuirt WT Prasad SD, Griffith AJ, Kunst HPM, et al. Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13) [J]. Nature Genet, 1999,23:413-419.
83. Melkoniemi, M, Brunner, HG, Manouvrier, S, et al. Autosomal recessive disorder otospondylomegaepiphyseal dysplasia is associated with loss-of-function mutations in the COL11A2 gene [J]. Am J Hum Genet, 2000,66: 368-377.
84. Vuoristo, MM, Pappas, JG, Jansen, V, et al. A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome [J]. Am J Med Genet, 2004, 130A: 160-164.
85. Zwaenepoel, I, Mustapha, M, Leibovici, M, et al. Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22 [J]. Proc. Nat. Acad. Sci, 2002, 99: 6240-6245.
86. Robertson NG, Lu L, Heller S, et al. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction [J]. Nature Genet, 1998, 20: 299-303.
87. Fransen, E, Verstreken, M, Verhagen, W. et al. High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene [J]. Hum Molec Genet, 1999, 8: 1425-1429.
88. Grabski R, Szul T, Sasaki T, et al. Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin [J]. Hum Genet, 2003,113:406-416.
89. Usami S, Takahashi K, Yuge I, et al. Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease [J]. Europ. J Hum Genet, 2003,11: 744-478.
90. Ahituv N, Sobe T, Robertson NG, et al. Genomic structure of the human unconventional myosin VI gene. Gene [J]. 2000,261: 269-275.
91. Melchionda S, Ahituv N, Bisceglia L, et al. MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss [J]. Am J Hum Genet, 2001, 69: 635-640.
92. Ahmed ZM, Morell RJ, Riazuddin S, et al. Mutations of MYO6 are associated with recessive deafness, DFNB37 [J]. Am J Hum Genet, 2003, 72: 1315-1322.
93. Mohiddin SA, Ahmed ZM, Griffith AJ, et al. Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MY06) (Letter) [J]. J Med Genet, 2004,41: 309-314.
94. Leal A, Endele S, Stengel C, et al. A novel myosin heavy chain gene in human chromosome 19ql3.3 [J]. Gene, 2003, 312: 165-171.
95. Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family [J]. J Biol Chem, 2004, 279;-2800-2808.
96. Donaudy F, Snoeckx R, Pfister M, et al. Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4) [J]. Am J Hum Genet, 2004, 74: 770-776.
97. Dose AC, Burnside B. Cloning and chromosomal localization of a human class III myosin [J]. Genomics, 2000, 67: 333-342.
98. Walsh T, Walsh V, Vreugde S, et al. From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30 [J]. Proc Nat Acad Sci, 2002,99:7518-7523.
99. Kelley PM, Weston MD, Chen ZY, et al. The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A) [J]. Genomics, 1997,40: 73-79.
100. Liu XZ, Walsh J, Mburu P, et al. Mutations in the myosin VILA gene cause non-syndromic recessive deafness [J]. Nature Genet, 1997,16: 188-190.
101. Weil D, Kussel P, Blanchard S, et al. The autosomal recessive isolated deafness, DFNB2, and the UsherlB syndrome are allelic defects of the myosin-VIIA gene [J]. Nature Genet, 1997, 16: 191-193.
102. Liu XZ, Walsh J, Tamagawa Y, et al. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene (Letter) [J]. Nature Genet, 1997,17: 268-269.
103. Weston MD, Kelley PM, Overbeck LD, et al. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients [J]. Am J Hum Genet, 1996, 59: 1074-1083.
104. Wang A, Liang Y, Fridell RA, et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3 [J]. Science, 1998, 280: 1447-1451.
105.Liburd N, Ghosh M, Riazuddin S, et al. Novel mutations of MYO15A associated withprofound deafness in consanguineous families and moderately severe hearing loss in a patientwith Smith-Magenis syndrome [J]. Hum Genet, 2001,109: 535-541. 106.Belyantseva LA, Boger ET, Naz S, et al. Myosin-XVa is required for tip localization ofwhirlin and differential elongation of hair-cell stereocilia [J]. Nature Cell Biol, 2005, 7:148-156.
107. Lynch ED, Lee MK, Morrow JE, et al. Nonsyndromic deafness DFNA1 associated with mutation of the human homolog of the Drosophila gene diaphanous [J]. Science, 1997, 278: 1315-1318.
108. Rose R, Weyand M, Lammers M, et al. Structural and mechanistic insights into the interaction between Rho and mammalian Dia (Letter) [J]. Nature, 2005,435: 513-518.
109.Lalwani AK, Goldstein JA, Kelley MJ, et al. Human nonsyndromic hereditary deafnessDFNA17 is due to a mutation in nonmuscle myosin MYH9 [J]. Am J Hum Genet, 2000, 67:1121-1128.
110.Martignetti JA, Heath KE, Harris J, et al. The gene for May-Hegglin anomaly localizes to aless than 1-Mb region on chromosome 22ql2.3-13.1 [J]. Am J Hum Genet, 2000, 66:1449-1454.
111.Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosinheavy chain A, in May-Hegglin anomaly [J]. Nature Genet, 2000, 26: 106-108.
112.Moxey-Mims MM, Young G, Silverman A, et al. End-stage renal disease in two pediatricpatients with Fechtner syndrome [J]. Pediat. Nephrol, 1999, 13: 782-786.
113. Siemens J, Kazmierczak P, Reynolds A, et al. The Usher syndrome proteins cadherin 23 andharmonin form a complex by means of PDZ-domain interactions [J]. Proc Nat Acad Sci, 2002,99: 14946-14951.
114.Boeda B, El-Amraoui A, Bahloul A, et al. harmonin and cadherin 23, three Usher I geneproducts that cooperate to shape the sensory hair cell bundle [J]. EMBO J, 2002, 21:6689-6699.
115.Erba HP, Eddy R, Shows T. Structure, chromosome location, and expression of the humangamma-actin gene: differential evolution, location, and expression of the cytoskeletal beta-and gamma-actin genes [J]. Molec Cell Biol, 1988,8: 1775-1789.
116.Ueyama H, Inazawa J, Nishino H, et al. FISH localization of human cytoplasmic actin genesACTB to 7p22 and ACTG1 to 17q25 and characterization of related pseudogenes [J].CytoGenet, Cell Genet, 1996, 74: 221 -224.
117.Zhu M, Yang T, Wei S, et al. Mutations in the gamma-actin gene (ACTG1) are associatedwith dominant progressive deafness (DFNA20/26) [J]. Am J Hum Genet, 2003, 73:1082-1091.
118. van Wijk E, Krieger E, Kemperman MH, et al. A mutation in the gamma actin 1 (ACTG1)gene causes autosomal dominant hearing loss (DFNA20/26) [J]. J Med Genet, 2003, 40:879-884.
119. Yasunaga S, Grati M, Cohen-Salmon M, et al. A mutation in OTOF, encoding otoferlin, aFER-1-like protein, causes DFNB9, a nonsyndromic form of deafness [J]. Nature Genet, 1999,21: 363-369.
120. Yasunaga S, Grati M, Chardenoux S, et al. OTOF encodes multiple long and short isoforms: Genetic evidence that the long ones underlie recessive deafness DFNB9 [J]. Am J Hum Genet, 2000, 67: 591-600.
121. Adato A, Raskin L, Petit C, et al. Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus [J]. Europ. J Hum Genet, 2000, 8: 437-442.
122.Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, et al. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss [J]. J Med Genet, 2002,39: 502-506.
123.Varga R, Kelley PM, Keats BJ, et al. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter) [J]. J Med Genet, 2003,40: 45-50.
124. Van Laer L, Huizing EH, Verstreken M, et al. Nonsyndromic hearing impairment is associated with a mutation in DFNA5 [J]. Nature Genetics, 1998, 20: 194-197.
125. Yu C, Meng X, Zhang S, Zhao G, et al. A 3-nucleotide deletion in the polypyrimidine tract of the intron 7 of the DFNA5 gene causes nonsyndromic hearing impairment in a Chinese family [J]. Genomics, 2003, 82: 575-579.
126. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome) [J]. Nature Genet, 1998,20: 143-148.
127.Domenech E, Gomez-Zaera M, Nunes V, et al. Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families [J]. Clin. Genet, 2004,65: 463-469.
128. Verpy E, Masmoudi S, Zwaenepoel I, et al. Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus [J]. Nature Genet, 2001, 29: 345-349.
129. Attardi G, Schatz G. Biogenesis of mitochondria [J]. Annual Review of Cell Biology. 1988,4: 289-333.
130. Wallace DC. Mitochondrial diseases in man and mouse [J]. Science, 1999,283: 1482-1488.
131.Schon EA, Bonilla E, Dimauro S. Mitochondrial ONA mutations and pathogenesis [J]. JBioenerg Biomembr. 1997,29: 131-149.
132.DiMauro S, Schon EA. Mitochondrial DNA mutations in human disease. American Journal of Medical Genetics, 2001,106(l):18 -26
133.Prezant TR, Agapian JV, Bohlman MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and nonsyndromic deafness [J]. Nat Genet, 1993, 4:289-294.
134. Guan, MX, Fishel-Ghodsian N, Attardi G. A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity [J]. Hum Mol. Genet, 2000, 9: 1787-1793.
135. Guan, MX. Molecular Pathogenetic Mechanism of Maternally Inherited Deafness [J]. Ann N YAcadSci, 2004, 259-271
136.Pandya A, Xia XJ, Erdenetungalag RM. et al. Heterogenous point mutations in the mitochondrial tRNASer(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia [J]. Am J Hum Genet, 1999, 65: 1803-1806.
137.Lopez-Bigas N, Rabionet R, Martinez E, et al. Mutations in the Mitochondrial tRNA Ser(UCN)and in the GJB2 (Connexin 26) Gene Are Not Modifiers of the Age at Onset or Severity of HearingLoss in Spanish Patients with the 12S rRNA A1555G Mutation [J]. Am J Hum Genet, 2000, 66:1465-1467
138.Torroni A, Cruciani F, Rengo C, et al. The A1555G mutation in the 12S rRNA gene of human mtDNA: Recurrent origins and founder events in families affected by sensorineural deafness [J]. Am J Hum Genet, 1999, 65:1349-1358.
139. Guan MX, Fischel-Ghodsian N, Attardi G. Biochemical evidence for nuclear gene involvementin phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation [J]. Human Molecular Genetics, 1996, 5: 963-971.
140. Guan MX, Fischel-Ghodsian N, Attardi G. Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation [J]. Hum Mol. Genet, 2001, 10: 573-580.
141.Bykhovskaya Y, Shohat M, Ehrenman K, et al. Evidence for complex nuclear inheritance in a pedigree with non-syndromic deafness due to a homoplasmic mitochondrial mutation [J].American Journal of Medical Genetics, 1998, 77:421-426.
142.Bykhovskaya Y, Yang H, Taylor K, et al. Modifier locus for mitochondrial DNA disease:Linkage and linkage disequilibrium mapping of a nuclear modifier gene for maternally inherited deafness [J]. Genetics in Medicine, 2001, 3: 177-180.
143.Bykhovskaya Y, Estivill X, Taylor K, et al. Candidate locus for a nuclear modifier gene formaternally inherited deafness [J]. Am J Hum Genet, 2000, 66:1905-1910. 144.Finnila S, Majamaa K. Lack of modulative factor in locus 8p23 in Finnish family with nonsyndromic sensorineural hearing loss associated with the 1555A>G mitochondrial DNA mutation [J]. European Journal of Human Genetics, 2003,11: 652-658.
145.Mitomap: Human Mitochondrial Genome Database. Center for Molecular Medicine Emory University, Atlanta, GA, USA World Wide Web (http://www.gen.emory.edu/mitomap.html),1995.
146.Arnaudo E, Hirano M, Seelan RS, et al. Tissue specific expression and chromosome assignment of genes specifying two isoforms of subunit Vila of human cytochrome c oxidase[J].Gene, 1992,119:299-305.
147. Bindoff LA, Howell N, Poulton J, et al. Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA [J]. J Biol Chem, 1993,268:19559-19564.
148. Fischel-Ghodsian N. Mitochondrial RNA Processing and Translation: Link between Mitochondrial Mutations and Hearing Loss [J]. Molecular Genetics and Metabolism, 1998, 65:97-104.
149. Johnson DF, Hamon, M, Fischel-Ghodsian N. Cloning and characterization of the human mitochondrial ribosomal S12 gene [J]. Genomics, 1998, 52, 363-368.
150. Bykhovskaya Y, Mengesha E, Wang D, et al. Human mitochondrial transcription factor Bl as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation [J]. Mol. Genet, Metab. 2004, 82:27-32.
151. Bykhovskaya Y, Mengesha E, Wang D, et al. Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTO1 and GTPBP3 [J]. Molecular Genetics and Metabolism, 2004, 83: 199-206.
152. Abe S, Kelley PM, Kimberling WJ, et al. Connexin 26 gene (GJB2) mutations modulates the severity of hearing loss associated with the 1555A—>G mitochondrial mutation [J]. Am J Med Genet, 2001, 103:334-338.
153. Bacino C, Prezant TR, Bu X, Fournier P, Fischel-Ghodsian N. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness [J]. Pharmaco Genetics, 1995, 5: 165-172.
154. Fischel-Ghodsian N. Mitochondrial deafness mutations reviewed [J]. Hum Mutat. 1999, 13: 261-270.
155. Li R, Greinwald JH., Yang L, et al. Molecular analysis of the mitochondrial 12S rRNA and tRNA-ser(UCN) genes in paediatric subjects with non-syndromic hearing loss [J]. Journal of Medical Genetics, 2004,41:615-620.
156.Thyagarajan D, Bressman S, Bruno C, et al. A novel mitochondrial 12SrRNA point mutation in parkinsonism, deafness, and neuropathy [J]. Ann. Neurol. 2000,48: 730-736.
157. Zhao H, Li R, Wang Q, et al. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family [J]. Am J Hum Genet, 2004, 74: 139-152.
158. Reid FM, Vernham GA, Jacobs HT. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness [J]. Hum Mutat, 1994, 3: 243-247.
159. Fischel-Ghodsian N, Prezant TR, Fournier P, et al. Mitochondrial mutation associated with nonsyndromic deafness [J]. Am J Otolaryng. 1995,16: 403-408.
160.Sevior KB, Hatamochi A, Stewart I. et al. Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness [J]. Am J Med Genet, 1998, 75: 179-185.
161.Guan MX, Enriquez JA, Fischel-Ghodsian N, et al. The deafness-associated mitochondrial DNA mutation at position 7445, which effects tRNAser(UCN) precursor processing, has long-range affects on NADH dehydrogenase subunit ND6 gene expression [J]. Molec CellBiol, 1998, 18: 5868-5879.
162.Tiranti V, Chariot P, Carella F, et al. Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNAser(UCN) gene [J]. Hum Molec Genet, 1995,4:1421-1427.
163. Verhoeven K, Ensink RJH, Tiranti V, et al. Hearing impairment and neurological dysfunction associated with a mutation in the mitochondrial tRNAser(UCN) gene [J]. Europ. J Hum Genet, 1999,7:45-51.
164.Toompuu M, Tiranti V, Zeviani M, et al. Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids [J]. Hum Molec Genet, 1999, 8: 2275-2283.
165.Hutchin TP, Parker MJ, Young ID, et al. A novel mutation in the mitochondrial tRNASer(UCN) gene in a family with non-syndromic sensorineural hearing impairment [J]. JMed Genet, 2000,37: 692-694.
166．严明．一例非综合征母系遗传耳聋大家系的分子遗传学研究[D]．博士论文
167．黄小义，刘岸，于旸，等．中国10个民族永生细胞系的建立与保存[J]．遗传，2002，24(6)，643-645．
168．乔军，刘亚琴，孙逸平，等．微量全血EB病毒转化法建立B淋巴细胞系的新技术[J]．中华实验临床免疫学杂志，1990，2：2．5．
169．李冬娜，区彩莹，陈路．建立海南黎族永生细胞库[J]。遗传，1999，21(6)：2l一22．
170．王子淑编．人体及动物细胞遗传学实验技术[M]．成都：四川大学出版社，1987．
171．周焰庚编．人类染色体[M]．北京：科学出版社，1987．
172．杨汉民著．细胞生物学实验[M]．北京：高等教育出版社2001，6．
173．卜行宽．常染色体显性遗传性感音性聋的大家系听力学调查[J]．中华耳鼻咽喉科杂志，1992，27：40．
174．郭汉璧，谭振涛，孙玉洁．显性遗传性聋大家系研究[J]．中国优生与遗传学杂志，1994， 2(2)：94—100．
175．Jaber L，Shohat M，Bu X．Sensorineural deafness inherited as a tissue specific mitochondrial disorder [J]．J Med Genet，1 992；29：86．
176．邢光前，卜行宽，严明，等．母系遗传性聋大家系听力学调查及线粒体DNA突变分析[J]． 中华耳鼻咽喉科杂志，2000，35：98—101．
177．严明，刘宁生，单祥年．一个母系遗传非综合征耳聋大家系及mtDNAl2SrRNA基因突变研究[J]．中华医学遗传学杂志，1999，5：321．325．
178.Torroni A, Rengo C, Guida V, et al. Do the four clades mtDNA haplogroupL2 evolve at different rate [J]. Am J Hum Genet, 2001, 69:1348-1356.
179. Li XM, Guan MX. A Human Mitochondrial GTP Binding Protein Related to tRNA Modification May Modulate Phenotypic Expression of the Deafness-Associated Mitochondrial 12S rRNA Mutation [J]. Mol Cell Biol, 2002, 22: 7701 - 7711.
180. Li XM, Li RH, Guan MX. Isolation and Characterization of the Putative Nuclear Modifier Gene MTOl Involved in the Pathogenesis of Deafhess-associated Mitochondrial 12 S rRNA A1555G Mutation [J]. J Biol Chem, 2002, 277: 27256 - 27264.
181. Wang YC, Kung CY, Su MC, et al. Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan [J]. Eur J Hum Genet, 2002,10:495-498
182.Bykhovskaya Y, Mengesha E, Wang D. Phenotype of non-syndromic deafness associated with the mitochondrial A1555G mutation is modulated by mitochondrial RNA modifying enzymes MTOl and GTPBP3 [J]. Mol Genet Metab, 2004, 83(3): 199-206.
1. 王宗仁,杜若甫.鹿科动物的染色体组型及其进化[J].动物学报(Wang Zong-ren, DuRuo-fu. Karyotypes of cervidae and their evolution. Acta Zoologica Sinica), 1983 , 29(3):214-221
2. 马世来,王应祥,徐龙辉. 麂属（Muntiacus ）的分类及其系统发育研究[J]. 兽类学报(Ma Shi-lai, Wang Yingxiang Taxonomic and phylogenetic studies on the genus muntiacus.Acta Theriologica Sinica), 1986, 6: 191 －207
3. SHI L M, MA C X. A new karyotype of muntjac(Muntiacus sp.) from Gongshan county in China[J]. Zoological Research, 1988, 9: 343-347
4. 王宗仁,杜若甫.1982 鹿属（Cervus ）染色体组型的进化[J]. 遗传学报(Wang Zong-ren,Du Ruo-fu. Evolution of karyotype of the genus Cervus. Acta Gentica Sinica), 1982,9(1):24-31
5. Wallace D C. Mitochondrial DNA Variation in Human Evolution, Degenerative Disease,and Aging[J]. Am. J. Hum. Genet, 1995, 57:201-223.
6. Zhang Ya-Ping, Oliver A. Ryder.Mitochondrial DNA Sequence Evolution in the Arctoidea[J]. Proc Natl Acad Sci USA, 1993, 90(20): 9557-9561.
7. Shi Yan-feng, Shan Xiang-nian Li-jian, Zhang Xiao-mei, Zhang Hai-jun. Sequencing and Organization of the Complete Mitochondrial Genome of Muntiacus muntjak[J]. Acta Zoologica Sinica, 2003, 49(5): 629-636
8. 兰宏,施立明.麂属（Muntiacus ）动物线粒体DNA 多态性及其遗传分化[J]. 中国科学（B）(Lan-Hong, Shi Li-ming. The Polymorphism and genetics differentiation of the Mitchondrial DNA of Muntiacus. Sciences in China(B) ), 1993, 23(5): 489-497
9. Avise J C. Molecular Markers, Natural History and Evolution [M]. Champman & Hall. New York. London. 1994, 511
10. Groves C P, Grubb P. Relationships of living deer [M]. In: Wemmer CM. Biology and Management of the Cervidae Washington, Smithsonia Inst Press, 1987, 21-59
11. Geist V. Endangered species and the law. Nature, 1992, 357: 274-276
12. Wang Wen, Lan Hong. Rapid and parallel chromosomal number reductions in Muntjac deer inferred from mitochondrial DNA phylogeny [J]. Mol. Biol. Evol, 2000, 17(9):1326-1333
13. Shi L M. Unique cytogenetic characteristics of a tufted deer Elaphodus cephalophus.Mamm [J]. Chromosome News1, 1981, 22: 47-51
14. Iwin D W, Kocher T D, Wilson A C. Evolution of the cytochrome b gene of mammals [J].J. Mol. Evol, 1999, 32: 128 –144
15. Irwin D M, Kocher T D, Wilson A C. Evolution of the cytochrome b gene of mammals [J]. J. Mol. Evol, 1991, 32:128-144
16. Johns G C, Avise J C. A comparative summary of genetic distances in the vertebrates from the mitochondrial cytochrome b gene [J]. Mol. Biol. Evol, 1998, 15(11):1481-1490.
17. 张亚平,Ryder O A.金丝猴属的DNA 序列变异及进化与保护遗传学研究[J].遗传学报(Zhang Ya-ping, Ryder O A. Mitochondrial DNA sequence evolution and conservation relevance of Snub-nosed Langurs Acta Gentica Sinica), 1997, 24(2): 116 －121
18. Bouvrain G., Geraads D, Jehenne Y. New data relating to the classification of the Cervidae (Artiodactyla, Mammalia) [J]. Zool. Znz, 1989, 223, 82-90
19. Ettore Randi, Nadia Mucci, Massimo Pierpaoli, Emmanuel Douzery. New phylogenetic perspectives on the Cervidae (Artiodactyla) are provided by the mitochondrial cytochrome b gene [J]. Pro. R. Soc. Lond.B,1998, 265, 793-801
20. 张亚平.从DNA 序列到物种树[J]. 动物学研究(Zhang Ya-ping. From DNA Sequence to Species Tree. Zoological Research), 1996, 17(3): 247-252
21. 张荣祖.中国自然地理－动物地理[M]. 科学出版社(Zhang Rong-zu. Physicalgeography of China- Zoo geography. Beijing: The Science Press ), 1980, 1-120
22. 易广才, 张小梅, 单祥年. 麂属(Muntiacus)动物线粒体12S RNA 细胞色素b 基因和多耐药基因序列的分析及其分子进化关系[J]. 遗传学报(Yi Guang-cai, Zhang Xiao-mei, Shan Xiang-nian. 12S rRNA Cytochrome b and MDR1 Gene DNA Sequence Phylogentic Evolution of Muntiacus [J]. Acta Gentica Sinica), 2002, 29(8): 674-680
23. 肖武汉, 张亚平. 鱼类线粒体DNA 的遗传与进化[J].水生生物学报(Xiao Wu-han,Zhang Ya-ping. Genetics and Evolution of Michondrial DNA in Fish. Acta Hydrobioloica Sinica), 2000, 24(4): 384-391