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Genomic Approaches to Discovery and Characterization of Genes for Inherited Hearing Loss

Award Number: R01DC011835
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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The goal of this project is to discover and characterize new genes for inherited hearing loss by studying highly informative families from the Middle East. Families from regions with traditions of consanguinity or endogamy have been particularly informative for gene discovery for hearing loss, with other mutations responsible for both recessive and dominant hearing losses subsequently identified in other families. Over the past 19 years, our partnership has discovered seven new genes for hearing loss, contributed to the genotype-phenotype profiles of many others, evaluated the roles of microRNAs in hearing development, and characterized the functions of our mutant genes in patient cells and mouse models. During the current grant period, we published SYNE4 as a new gene for hearing loss and are in the midst of functional studies of five other candidate genes: ATOH1, CDKL3, CTBS, GOSR2, and OTOP2. We have also been at the forefront of application of genomic technologies to hearing research. We were among the first groups to apply exome sequencing to gene discovery for any phenotype and to develop targeted hybridization pools for thorough and efficient screening of candidate deafness genes. Our partnership has complementary strengths at Tel Aviv University, Bethlehem University, and the University of Washington in Seattle. Our greatest asset is our relationship with hundreds of highly informative Palestinian and Israeli families, each with multiple relatives with hearing loss who have been evaluated by audiology and for syndromic features. Complete families participate, are willing to be re-contacted, and remain in touch with us indefinitely. In Aim 1, we will enroll each year all informative members of 80-100 multiplex Palestinian and Israeli families (400-500 individuals) with hearing loss, and use our targeted gene panel to sequence for mutations in known genes for hearing loss. In Aim 2, families not resolved by Aim 1 will be evaluated by whole genome sequencing. Variants prioritized for functional studies will be rare coding sequence variants of predicted damaging effect in new candidate genes that co-segregate with hearing loss; and rare non-coding variants that lie in potential regulatory regions, as defined by several parameters, and that co-segregate with hearing loss. In Aim 3, we will undertake functional studies of these new candidate genes and mutations. Our approaches will include functional analysis of wild type and mutant proteins in transfected cells and cochlear explants, and generation of mouse models of mutations from human families by CRISPR/Cas9 genome editing, followed by characterization of their hearing and inner ear phenotypes. In summary, we propose to use modern tools of genetics and genomics to reveal and characterize genes essential for development and maintenance of hearing. Our discoveries will aid in the development of biological strategies for treatment or cures for deafness.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $471,178 )
2022	2022	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA				ISR	Research Related to Deafness and Communication Disorders	000	10	6/1/2022	NON-COMPETING CONTINUATION	$471,178
														Subtotal = $471,178

Issue Date FY: 2021 ( Subtotal = $478,671 )
2021	2021	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA				ISR	Research Related to Deafness and Communication Disorders	000	9	6/2/2021	NON-COMPETING CONTINUATION	$478,671
														Subtotal = $478,671

Issue Date FY: 2020 ( Subtotal = $483,903 )
2020	2020	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA		006905904		ISR	Research Related to Deafness and Communication Disorders	000	8	5/21/2020	NON-COMPETING CONTINUATION	$483,903
														Subtotal = $483,903

Issue Date FY: 2019 ( Subtotal = $490,140 )
2019	2019	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA		006905904		ISR	Research Related to Deafness and Communication Disorders	000	7	5/9/2019	NON-COMPETING CONTINUATION	$490,140
														Subtotal = $490,140

Issue Date FY: 2018 ( Subtotal = $513,179 )
2018	2018	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA		006905904		ISR	Research Related to Deafness and Communication Disorders	001	6	5/16/2018	COMPETING CONTINUATION	$513,179
2018	2015	TEL AVIV UNIVERSITY	55 LEBANON HAIM	TEL AVIV-JAFFA		006905904		ISR	Research Related to Deafness and Communication Disorders	000	5	11/29/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $513,179

Issue Date FY: 2015 ( Subtotal = $211,227 )
2015	2015	TEL AVIV UNIVERSITY	**	TEL AVIV				ISR	Research Related to Deafness and Communication Disorders	000	5	6/11/2015	NON-COMPETING CONTINUATION	$211,227
														Subtotal = $211,227

Issue Date FY: 2014 ( Subtotal = $213,360 )
2014	2014	TEL AVIV UNIVERSITY	**	TEL AVIV				ISR	Research Related to Deafness and Communication Disorders	000	4	6/6/2014	NON-COMPETING CONTINUATION	$213,360
														Subtotal = $213,360

Issue Date FY: 2013 ( Subtotal = $202,693 )
2013	2013	TEL AVIV UNIVERSITY	RAMAT-AVIV	TEL AVIV				ISR	Research Related to Deafness and Communication Disorders	000	3	6/13/2013	EXTENSION WITH OR WITHOUT FUNDS	$202,693
														Subtotal = $202,693

Issue Date FY: 2012 ( Subtotal = $213,360 )
2012	2012	TEL AVIV UNIVERSITY	RAMAT-AVIV	TEL AVIV				ISR	Research Related to Deafness and Communication Disorders	000	2	5/18/2012	NON-COMPETING CONTINUATION	$213,360
														Subtotal = $213,360

Issue Date FY: 2011 ( Subtotal = $212,500 )
2011	2011	TEL AVIV UNIVERSITY	RAMAT-AVIV	TEL AVIV				ISR	Research Related to Deafness and Communication Disorders	000	1	6/30/2011	NEW	$212,500
														Subtotal = $212,500

Grand Total All Awards = $3,490,211

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Genomic Approaches to Discovery and Characterization of Genes for Inherited Hearing Loss

Award Number: R01DC011835

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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