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A Collaborative Search for New Genes for Non-Syndromic Deafness

合作寻找非综合征性耳聋的新基因

基本信息

批准号：
10396975
负责人：
MUSTAFA TEKIN
金额：
$ 64.43万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10396975
关键词：
ATAC-seq Affect Bioinformatics Biological Birth CRISPR interference CRISPR/Cas technology Candidate Disease Gene Cell physiology Cells Child Chromatin Chromosome 8 Clinic Clinical Data Clinical Management Cochlea Code Consanguinity Counseling DNA Data Databases Diagnosis Enhancers Etiology FRAP1 gene Family Foundations Functional disorder Gene Expression Genes Genetic Genetic Counseling Genetic Transcription Genomics Goals Hearing Human Human Cell Line In Vitro Inbreeding Individual Infant Integral Membrane Protein International Knock-in Mouse Knock-out Knowledge Link Mediating Modeling Molecular Molecular Diagnosis Molecular Diagnostic Testing Morphology Mus Mutant Strains Mice Mutate Mutation Newborn Infant Nucleic Acid Regulatory Sequences Outcome Parents Pathway interactions Persons Pharmaceutical Preparations Phenotype Population Principal Investigator Regulatory Element Research Personnel Role Sampling Signal Transduction Site Syndrome Testing Therapeutic Therapeutic Intervention Time Translating Universities Untranslated RNA Variant analysis pipeline autosomal recessive trait base causal variant clinical translation clinically significant deaf deafness diagnostic tool exome sequencing experimental study gene discovery gene therapy genetic deafness genetic testing genetic variant genome analysis genome sequencing growth differentiation factor 6 hearing impairment improved in vitro Model loss of function member molecular diagnostics mouse genome mouse model mutant normal hearing notch protein novel precursor cell programs progressive hearing loss repository reproductive single-cell RNA sequencing standard of care success

项目摘要

Program Director/Principal Investigator (Last, First, Middle): Project Summary Clinically significant hearing loss is present in at least 1.9 per 1,000 infants at birth and affects nearly half of the population at some time in their lives. Nearly 70% of congenital or 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 finding (NSHL). DNA variants in currently recognized deafness genes are not detected in more than one-third of affected individuals with autosomal recessive NSHL, leaving large number of families without a molecular diagnosis. We established a repository that contains biological samples and clinical data on about three thousand families with NSHL. Of these, over a thousand include at least two affected members and are consistent with autosomal recessive NSHL. The most common forms of NSHL have been excluded in all families; all known deafness genes were excluded in over four hundred families. We will use genome sequencing to identify underlying coding and non-coding variants in families with autosomal recessive NSHL that remain unsolved in our Repository. Availability of a large number of inbred families will facilitate analysis within autozygous regions. To support the role of identified variants in pathophysiology, we will perform functional experiments utilizing in vitro and mouse models. We have successfully applied this strategy to discover novel deafness genes during the previous cycles of this application. Detected variants and associated audio-vestibular phenotypes will be stored in a database that will be accessible by outside researchers. The outcomes of this proposal will be discoveries of novel coding and non-coding variants in genes and pathways involved in the pathophysiology of deafness, foundation of molecular diagnostic tests for etiological diagnosis, counseling, and candidacy for molecular treatments of affected individuals. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

项目主管/首席研究员（后、一、中）：