More than 60% of prelingual deafness is genetic in origin, and of these up to 93% are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only abnormality. While causal mutations have been identified in one of 31 different genes in a subset of patients with non-syndromic autosomal recessive sensorineural hearing loss, at least 40% of families do not have an identifiable mutation nor do they demonstrate linkage to any known gene. Moreover, the distribution of recognized genetic causes in different populations as well as mutation specific phenotypes remains unknown. Recent advances in molecular technologies provide unprecedented opportunities to genotype dense arrays of SNP markers throughout the genome and to sequence large segments of the human genome with ease. Turkey provides a very valuable resource for the identification of new genes for deafness because it has been continually inhabited since ancient times and much of the population still lives in about 40,000 small villages throughout the country, where consanguinity is the cultural norm. There is also a high level of assortative mating among the deaf and a very long history of the use of sign language in specific areas of Turkey. All of these factors are known to have a profound influence on the survival, expression and spread of new mutations for deafness. We have ascertained 247 inbred multiplex Turkish families with autosomal recessive non-syndromic hearing loss. We will recruit >100 additional families with the same characteristics which will lead to creation of an excellent repository that can be used to identify many of the remaining genes for autosomal recessive non-syndromic deafness. After exclusion of common known genes, we will have ~150 families to discover and confirm new genes for deafness. We will use genome wide dense SNP arrays to find new loci for deafness and identify causative mutations with either traditional or next-generation sequencing. We have already discovered a new deafness gene in one family using the proposed strategy, clearly demonstrating the utility of this invaluable resource. The Repository will be made available to external investigators upon completion of this proposal.

Public Health Relevance

This project is a collaborative study of genetic deafness involving investigators from the United States and Turkey. The goals of the project are to identify new loci and new genes for non-syndromic deafness and to establish a resource for research on genetic deafness including biological samples and clinical data from large numbers of families in Turkey. The outcome of this proposal will expand the scientific knowledge on the genomic basis of hereditary deafness.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009645-05
Application #
8663586
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Watson, Bracie
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
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Atik, Tahir; Koparir, Asuman; Bademci, Guney et al. (2015) Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome. Orphanet J Rare Dis 10:128

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