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A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17


Two percent of the residents of Bengkala, Bali, have profound, congenital, neurosensory, nonsyndromal deafness due to an autosomal recessive mutation at the DFNB3 locus. We have employed a direct genorne–wide disequilibrium search strategy, allele–frequency–dependent homozygosity mapping (AHM), and an analysis of historical recombinants to map DFNB3 and position the locus relative to flanking markers. DFNB3 maps to chromosome 17, closest to D17S261, pRM7–GT and D17S805. In individuals homozygous for DFNB3, historical recombinant genotypes for the flanking markers, D17S122 and D17S783, place DFNB3 in a 5.3 cM interval of the pericentromeric region of chromosome 17 on a refined linkage map of 17p–17q12. Based on conserved synteny, the murine sh2 gene may be the homologue of DFNB3.

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  1. 1

    Morton, N.E. Genetic epidemiology of hearing impairment. Genetics of Hearing Impairment (eds Ruben, R.J., Van DeWater, T.R. & Steel, K.P.) 630, 16–31 (New York Academy of Sciences, New York, 1991).

    Google Scholar 

  2. 2

    Nance, W.E. & McConnell, F.E. Status and prospects in hereditary deafness. In Advances in Human Genetics, (eds Harris, H. & Hirschhom, K.) 4, 173–237 (Plenum Press, New York, 1973).

    Chapter  Google Scholar 

  3. 3

    Nance, W.E. & Sweeney, A. Genetic factors in deafness of early life. Otolaryngologic Clinic of North America 8, 19–48 (1975).

    CAS  Google Scholar 

  4. 4

    Marres, H.A.M. & Cramers, W.R.J. Autosomal recessive nonsyndromal profound childhood deafness in a large pedigree. Arch. Otolaryngol. Head Neck Surg. 115, 591–595 (1989).

    CAS  Article  Google Scholar 

  5. 5

    Steele, M.W. Genetics of congenital deafness. Ped. Clin. North Am. 28, 973–980 (1981).

    CAS  Article  Google Scholar 

  6. 6

    Stevenson, A.C. & Cheeseman, E.A. Hereditary deaf mutism, with particular reference to Northern Ireland. Ann. hum. Genet. 20, 177–234 (1956).

    CAS  Article  Google Scholar 

  7. 7

    Brownstein, Z., Friedlander, Y., Peritz, E. & Cohen, T. Estimated number of loci for autosomal recessive severe nerve deafness within the Israeli Jewish population, with implications for genetic counseling. Am. J. med. Genet. 41, 306–312 (1991).

    CAS  Article  Google Scholar 

  8. 8

    Chung, C.S. & Brown, K.S. Family studies of early childhood deafness ascertained through the Clarke school for the deaf. Am. J. hum. Genet. 22, 630–640 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Winata, S. et al. Congenital nonsyndromal autosomal recessive deafness in Bengkala, an isolated Balinese village. J. med Genet. (in the press).

  10. 10

    Weber, J.L. & Wong, C. Mutation of short tandem repeats. Hum. molec. Genet. 2, 1123–1128 (1993).

    CAS  Article  Google Scholar 

  11. 11

    Ott, J. Strategies for characterizing highly polymorphic markers in human gene mapping. Am. J. hum. Genet. 51, 283–290 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Lander, E.S. & Botstein, D. Homozygosity mapping: A way to map human recessive traits with DNA of inbred children. Science 236, 1567–1570 (1987).

    CAS  Article  Google Scholar 

  13. 13

    Mueller, R.F. & Bishop, D.T. Autozygosity mapping, complex consanguinity and autosomal recessive hearing impairment gene. Hered. Deaf. Newsletter 9, 14–15 (1992).

    Google Scholar 

  14. 14

    Sirugo, G. et al. Friedreich Ataxia in Louisiana Acadians: demonstration of a founder effect by analysis of microsatellite-generated extended haplotypes. Am. J. hum. Genet. 50, 559–566 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Hastbacka, J., Kaitila, I., Sistonen, P. & de la Chapelle, A. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nature Genet. 2, 204–211 (1992).

    CAS  Article  Google Scholar 

  16. 16

    Ott, J. Analysis of human genetic linkage (Johns Hopkins Press, Baltimore, 1991).

    Google Scholar 

  17. 17

    Weeks, D.E., Ott, J. & Lathrop, G.M. SLINK: a general simulation program for linkage analysis. Am J. hum. Genet. 47, A204 (1990).

    Google Scholar 

  18. 18

    Weber, J.L. et al. Evidence for human melotic recombination interference obtained through construction of a short tandem repeat-polymorphism linkage map of chromosome 19. Am. J. hum. Genet. 53, 1079–1095 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Pentao, L., Wise, C.A., Chinault, C., Patel, P.I. & Lupski, J.R. Charcot-Marie-Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet. 2, 292–300 (1993).

    Article  Google Scholar 

  20. 20

    Chevillard, C. et al. Relationship between Charcot-Marie-Tooth 1A and Smith-Magenis regions. snU3 may be a candidate gene for the Smith-Magenis syndrome. Hum. molec. Genet. 2, 1235–1243 (1993).

    CAS  Article  Google Scholar 

  21. 21

    Chance, P.F. et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72, 143–151 (1993).

    CAS  Article  Google Scholar 

  22. 22

    Roa, B.B., Dyck, P.J., Marks, H.G., Chance, P.F. & Lupski, J.R. Dejerine-Sottas syndrome associated with point mutation In the peripheral myelin protein 22 (PMP22) gene. Nature Genet. 5, 269–273 (1993).

    CAS  Article  Google Scholar 

  23. 23

    Roa, B.B. et al. Charcot-Marie-Tooth disease type 1A associated with a spontaneous point mutation In the PMP22 gene. New Engl. J. Med. 329, 96–101 (1993).

    CAS  Article  Google Scholar 

  24. 24

    Valentijn, L.J. et al. The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A. Nature Genet. 1, 166–170 (1992).

    CAS  Article  Google Scholar 

  25. 25

    Morell et al. Analysis of short tandem repeat (STR) allele frequency distributions in a Balinese population. Hum. molec. Genet., (in the press).

  26. 26

    Greenberg, F. et al. Molecular analysis of the Smith-Magenis syndrome: A possible contiguous-gene syndrome associated with del (17) (p11.2). Am. J. hum. Genet. 49, 1207–1218 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Guilford, P. et al. A non-syndromic form of neurosensory, recessive deafness maps to the pericentromeric region of chromosome 13q. Nature Genet. 6, 24–28 (1994).

    CAS  Article  Google Scholar 

  28. 28

    Guilford, P. et al. A human gene responsible for neurosensory, nonsyndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. Hum. molec. Genet. 3, 989–993 (1994).

    CAS  Article  Google Scholar 

  29. 29

    Ross, D.A., Kennerson, M.L. & Nicholson, G.A. Identification of fourteen potential sequences (HTF islands) in the CMT1A duplication/HNPP deletion area. Am. J. hum. Genet. 53, 1351 (1993).

    Google Scholar 

  30. 30

    Steel, K.P. Similarities between mice and humans with hereditary deafness. In Genetics of Hearing Impairment, (eds Ruben, R.J., Van DeWater, T.R. & Steel, K.P.) 630, 68–79 (New York Academy of Sciences, New York, 1991).

    Google Scholar 

  31. 31

    Lyon, M.F. & Kirby, M.C. Mouse chromosome atlas. Mouse Genome 91, 61 (1993).

    Google Scholar 

  32. 32

    Welcher, A.A., Suter, U., De Leon, M., Snipes, G.J. & Shooter, E.M. A myelin protein is encoded by the homologue of a growth arrest-specific gene. Proc. natn. Acad. Sci. U.S.A. 88, 7195–7199 (1991).

    CAS  Article  Google Scholar 

  33. 33

    Suter, U. et al. Trembler mouse carries a point mutation in a myelin gene. Nature 356, 241–244 (1992).

    CAS  Article  Google Scholar 

  34. 34

    Buetow, K.H. et al. Integrated human genome-wide maps constructed using CEPH reference panel. Nature Genet. 6, 391–393 (1994).

    CAS  Article  Google Scholar 

  35. 35

    Anderson, L.A. et al. High-density genetic map of the BRCA1 region of chromosome 17q12–q21. Genomics 17, 618–623 (1993).

    CAS  Article  Google Scholar 

  36. 36

    Abel, K.J. et al. A radiation hybrid map of the BRCA1 region of chromosome 17q12–q21. Genomics 17, 632–641 (1993).

    CAS  Article  Google Scholar 

  37. 37

    Flejter, W.L. et al. Multicolor FISH mapping with Alu-PCR-Amplified YAC clone DNA determines the order of markers in the BRCA1 region on chromosomes 17q12–q21. Genomics 17, 624–631 (1993).

    CAS  Article  Google Scholar 

  38. 38

    Weber, J.L. Know thy genome. Nature Genet. 7, 343–344 (1994).

    CAS  Article  Google Scholar 

  39. 39

    Reed, P.W. et al. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nature Genet. 7, 390–395 (1994).

    CAS  Article  Google Scholar 

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Friedman, T., Liang, Y., Weber, J. et al. A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat Genet 9, 86–91 (1995).

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