Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss

被引:370
作者
Noben-Trauth, K
Zheng, QY
Johnson, KR
机构
[1] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, NIH, Rockville, MD 20850 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
D O I
10.1038/ng1226
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23(753A) allele causes in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors is a primary determinant of AHL in mice.
引用
收藏
页码:21 / 23
页数:3
相关论文
共 15 条
[1]   Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle [J].
Boëda, B ;
El-Amraoui, A ;
Bahloul, A ;
Goodyear, R ;
Daviet, L ;
Blanchard, S ;
Perfettini, I ;
Fath, KR ;
Shorte, S ;
Reiners, J ;
Houdusse, A ;
Legrain, P ;
Wolfrum, U ;
Richardson, G ;
Petit, C .
EMBO JOURNAL, 2002, 21 (24) :6689-6699
[2]   Genetic basis for susceptibility to noise-induced hearing loss in mice [J].
Davis, RR ;
Newlander, JK ;
Ling, XB ;
Cortopassi, GA ;
Krieg, EF ;
Erway, LC .
HEARING RESEARCH, 2001, 155 (1-2) :82-90
[3]   Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D [J].
Di Palma, F ;
Holme, RH ;
Bryda, EC ;
Belyantseva, IA ;
Pellegrino, R ;
Kachar, B ;
Steel, KP ;
Noben-Trauth, K .
NATURE GENETICS, 2001, 27 (01) :103-107
[4]   GENETICS OF AGE-RELATED HEARING-LOSS IN MICE .1. INBRED AND F1-HYBRID STRAINS [J].
ERWAY, LC ;
WILLOTT, JF ;
ARCHER, JR ;
HARRISON, DE .
HEARING RESEARCH, 1993, 65 (1-2) :125-132
[5]   Ahl2, a second locus affecting age-related hearing loss in mice [J].
Johnson, KR ;
Zheng, QY .
GENOMICS, 2002, 80 (05) :461-464
[6]   A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice [J].
Johnson, KR ;
Zheng, QY ;
Bykhovskaya, Y ;
Spirina, O ;
Fischel-Ghodsian, N .
NATURE GENETICS, 2001, 27 (02) :191-194
[7]   A major gene affecting age-related hearing loss is common to at least ten inbred strains of mice [J].
Johnson, KR ;
Zheng, QY ;
Erway, LC .
GENOMICS, 2000, 70 (02) :171-180
[8]   mdfw: A deafness susceptibility locus that interacts with deaf waddler (dfw) [J].
NobenTrauth, K ;
Zheng, QY ;
Johnson, KR ;
Nishina, PM .
GENOMICS, 1997, 44 (03) :266-272
[9]   Molecular genetics of hearing loss [J].
Petit, C ;
Levilliers, J ;
Hardelin, JP .
ANNUAL REVIEW OF GENETICS, 2001, 35 :589-646
[10]   The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions [J].
Siemens, J ;
Kazmierczak, P ;
Reynolds, A ;
Sticker, M ;
Littlewood-Evans, A ;
Müller, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :14946-14951