Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.

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Serval ID
serval:BIB_104D693F8323
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
Journal
Plos One
Author(s)
Nishiguchi K.M., Rivolta C.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
7
Number
7
Pages
e41902
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: Retinitis pigmentosa and other hereditary retinal degenerations (HRD) are rare genetic diseases leading to progressive blindness. Recessive HRD are caused by mutations in more than 100 different genes. Laws of population genetics predict that, on a purely theoretical ground, such a high number of genes should translate into an extremely elevated frequency of unaffected carriers of mutations. In this study we estimate the proportion of these individuals within the general population, via the analyses of data from whole-genome sequencing.
METHODOLOGY/PRINCIPAL FINDINGS: We screened complete and high-quality genome sequences from 46 control individuals from various world populations for HRD mutations, using bioinformatic tools developed in-house. All mutations detected in silico were validated by Sanger sequencing. We identified clear-cut, null recessive HRD mutations in 10 out of the 46 unaffected individuals analyzed (∼22%).
CONCLUSIONS/SIGNIFICANCE: Based on our data, approximately one in 4-5 individuals from the general population may be a carrier of null mutations that are responsible for HRD. This would be the highest mutation carrier frequency so far measured for a class of Mendelian disorders, especially considering that missenses and other forms of pathogenic changes were not included in our assessment. Among other things, our results indicate that the risk for a consanguineous couple of generating a child with a blinding disease is particularly high, compared to other genetic conditions.
Pubmed
Web of science
Open Access
Yes
Create date
15/08/2012 12:16
Last modification date
20/08/2019 12:37
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