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Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian

Summary: ARTICLE
Five novel loci for inherited hearing loss mapped
by SNP-based homozygosity profiles in Palestinian
Hashem Shahin1,5, Tom Walsh*,2,5, Amal Abu Rayyan1, Ming K Lee2, Jake Higgins2,6, Diane Dickel3,
Kristen Lewis3, James Thompson3, Carl Baker3, Alex S Nord3, Sunday Stray2, David Gurwitz4,
Karen B Avraham4, Mary-Claire King2,3 and Moien Kanaan1
In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity
mapping with SNP arrays is an effective approach for gene discovery. In 20 Palestinian kindreds with prelingual nonsyndromic
hearing loss, we generated homozygosity profiles reflecting linkage to the phenotype. Family sizes ranged from small nuclear
families with two affected children, one unaffected sibling, and parents to multigenerational kindreds with 12 affected relatives.
By including unaffected parents and siblings and screening 250 K SNP arrays, even small nuclear families yielded informative
profiles. In 14 families, we identified the allele responsible for hearing loss by screening a single candidate gene in the longest
homozygous region. Novel alleles included missense, nonsense, and splice site mutations of CDH23, MYO7A, MYO15A, OTOF,
PJVK, Pendrin/SLC26A4, TECTA, TMHS, and TMPRSS3, and a large genomic deletion of Otoancorin (OTOA). All point
mutations were rare in the Palestinian population (zero carriers in 288 unrelated controls); the carrier frequency of the OTOA
genomic deletion was 1%. In six families, we identified five genomic regions likely to harbor novel genes for human hearing
loss on chromosomes 1p13.3 (DFNB82), 9p23p21.2/p13.3q21.13 (DFNB83), 12q14.3q21.2 (DFNB84; two families),
14q23.1q31.1, and 17p12q11.2 (DFNB85).
European Journal of Human Genetics (2010) 18, 407413; doi:10.1038/ejhg.2009.190; published online 4 November 2009


Source: Avraham, Karen - Department of Human Genetics and Molecular Medicine, Tel Aviv University


Collections: Biology and Medicine