Identification of Autosomal Recessive Non-syndromic Hearing Impairment Genes Non-syndromic hearing impairment (NSHI) is the most heterogeneous trait known, with >150 mapped loci and >70 identified genes. However, the vast majority of NSHI genes have neither been localized nor identified. The extreme genetic heterogeneity of NSHI is due to the different processes which can malfunction within the inner ear and cause the hearing impairment (HI) phenotype. For autosomal recessive (AR) NSHI usually only consanguineous pedigrees are sufficiently large enough to map and identify novel genes. Therefore the Pakistani population is ideal to identify ARNSHI genes due to the high rates of consanguinity. To date we have ascertained 445 Pakistani families with ARNSHI which have undergone a genome scan and linkage analysis. We are continuing to ascertain ARNSHI families and localize NSHI genes. Thus far we have identified the NSHI gene for 173 of these families and 156 families map to a region containing a known gene. Of the 116 families for which the gene has not been identified and there is no known gene within the linkage region, 22 families have established linkage (LOD score >3.3) to 19 unique genomic regions, 53 families display strongly suggestive linkage (2.0 Studying families from Pakistan, which have high rates of consanguinity, will aid in the identification of autosomal recessive nonsyndromic hearing impairment (NSHI) genes. The latest sequencing technologies will be performed to identify novel hearing impairment genes using DNA samples from Pakistani families with autosomal recessive NSHI. The identified genes will also be followed up using DNA samples from Middle Eastern, European and African- American families.Public Health Relevance
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