Usher syndrome in the Samaritans : Strengths and limitations of using inbred isolated populations to identify genes causing recessive disorders

B BONNE-TAMIR; A NYSTUEN; E SEROUSSI; H KALINSKY; A. E KWITEK-BLACK; M KOROSTISHEVSKY; A ADATO; V. C SHEFFIELD

doi:10.1002/(SICI)1096-8644(199710)104:2<193::AID-AJPA5>3.0.CO;2-%23

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Journal article

Usher syndrome in the Samaritans : Strengths and limitations of using inbred isolated populations to identify genes causing recessive disorders

B BONNE-TAMIR, A NYSTUEN, E SEROUSSI, H KALINSKY, A. E KWITEK-BLACK, M KOROSTISHEVSKY, A ADATO and V. C SHEFFIELD

American journal of physical anthropology, Vol.104(2), pp.193-200

1997

DOI: 10.1002/(SICI)1096-8644(199710)104:2<193::AID-AJPA5>3.0.CO;2-%23

PMID: 9386826

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Abstract

We have previously reported significant linkage between markers on 11q13.5 and Usher syndrome type 1 (USH1B) in a large Samaritan kindred. USH1B is an autosomal recessive disease characterized by profound congenital sensorineural deafness, vestibular dysfunction and progressive visual loss. A unique haplotype found only in all USH1B carriers and affected individuals implied that the disease-causing mutation probably entered the community from a single founder. Screening for mutations in a gene called GARP, which was mapped to the same genetic interval as USH1B, revealed a base substitution in the coding region of the gene, in a homozygous state in all affected individuals. This base substitution, which results in an arginine to tryptophane change, is not found in control individuals and occurs at an amino acid residue that is conserved across species, including mouse, gorilla, chimpanzee and macaque. This study emphasizes the strength of using an isolated inbred population for efficient identification of the primary linkage and for narrowing the disease interval, but also demonstrates its limitations in distinguishing between mutations causing the disease and those representing unique and private polymorphisms.

Ethnology

Morphological source materials

Physical anthropology, ethnobiology

Human ecology, environment

Details

Title: Subtitle: Usher syndrome in the Samaritans : Strengths and limitations of using inbred isolated populations to identify genes causing recessive disorders
Creators: B BONNE-TAMIR - Department of Human Genetics, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
A NYSTUEN - Department of Pediatrics and Ophthalmology, University of Iowa, Iowa City, Iowa 52242, United States
E SEROUSSI - Department of Human Genetics, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
H KALINSKY - Department of Human Genetics, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
A. E KWITEK-BLACK - Department of Pediatrics and Ophthalmology, University of Iowa, Iowa City, Iowa 52242, United States
M KOROSTISHEVSKY - Department of Human Genetics, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
A ADATO - Department of Human Genetics, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
V. C SHEFFIELD - Department of Pediatrics and Ophthalmology, University of Iowa, Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: American journal of physical anthropology, Vol.104(2), pp.193-200
Publisher: Wiley-Liss; New York, NY
DOI: 10.1002/(SICI)1096-8644(199710)104:2<193::AID-AJPA5>3.0.CO;2-%23
PMID: 9386826
ISSN: 0002-9483
eISSN: 1096-8644
Language: English
Date published: 1997
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9984065490902771

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