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

<h4>Background</h4>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 g...

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Autores principales:	Koji M Nishiguchi, Carlo Rivolta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b493994434045e7af0e05744d37ca3a
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spelling	oai:doaj.org-article:7b493994434045e7af0e05744d37ca3a2021-11-18T07:10:39ZGenes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.1932-620310.1371/journal.pone.0041902https://doaj.org/article/7b493994434045e7af0e05744d37ca3a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848652/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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%).<h4>Conclusions/significance</h4>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.Koji M NishiguchiCarlo RivoltaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41902 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Koji M Nishiguchi Carlo Rivolta Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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%).<h4>Conclusions/significance</h4>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.
format	article
author	Koji M Nishiguchi Carlo Rivolta
author_facet	Koji M Nishiguchi Carlo Rivolta
author_sort	Koji M Nishiguchi
title	Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
title_short	Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
title_full	Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
title_fullStr	Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
title_full_unstemmed	Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
title_sort	genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7b493994434045e7af0e05744d37ca3a
work_keys_str_mv	AT kojimnishiguchi genesassociatedwithretinitispigmentosaandallieddiseasesarefrequentlymutatedinthegeneralpopulation AT carlorivolta genesassociatedwithretinitispigmentosaandallieddiseasesarefrequentlymutatedinthegeneralpopulation
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Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.

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