Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

Background: Mutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ~46%, ~21% and...

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Detalhes bibliográficos
Autores: Fachal Vilar, Laura, Rodríguez Pazos, Laura, Ginarte Val, Manuel Javier, Toribio Pérez, Jaime, Salas Ellacuriaga, Antonio, Vega Gliemmo, Ana
Tipo de documento: artigo
Data de publicação:2012
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositório:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/4880
Acesso em linha:http://hdl.handle.net/20.500.11940/4880
Access Level:Acceso aberto
Palavra-chave:Founder Effect
Genes, Recessive
Haplotypes
Ichthyosis
Proteínas de Choque Térmico
Efecto Fundador
Genes Recesivos
Haplotipos
Ictiosis
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repository_id_str
spelling Multiple Local and Recent Founder Effects of TGM1 in Spanish FamiliesFachal Vilar, LauraRodríguez Pazos, LauraGinarte Val, Manuel JavierToribio Pérez, JaimeSalas Ellacuriaga, AntonioVega Gliemmo, AnaFounder EffectGenes, RecessiveHaplotypesIchthyosisProteínas de Choque TérmicoEfecto FundadorGenes RecesivosHaplotiposIctiosisBackground: Mutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ~46%, ~21% and ~13% of all TGM1 gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region. Methodology/principal findings: In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the TGM1 gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry. Conclusions/significance: In good agreement with the documentation record and the census, both mutations arose between 2,800-2,900 years ago (y.a.), but their TMRCA was in the range 600-1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on TGM1 haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900-4,500 y.a. (95% highest posterior density) followed by exponential growth.2012info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.11940/4880reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/48802026-06-12T08:40:47Z
dc.title.none.fl_str_mv Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
title Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
spellingShingle Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
Fachal Vilar, Laura
Founder Effect
Genes, Recessive
Haplotypes
Ichthyosis
Proteínas de Choque Térmico
Efecto Fundador
Genes Recesivos
Haplotipos
Ictiosis
title_short Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
title_full Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
title_fullStr Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
title_full_unstemmed Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
title_sort Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
dc.creator.none.fl_str_mv Fachal Vilar, Laura
Rodríguez Pazos, Laura
Ginarte Val, Manuel Javier
Toribio Pérez, Jaime
Salas Ellacuriaga, Antonio
Vega Gliemmo, Ana
author Fachal Vilar, Laura
author_facet Fachal Vilar, Laura
Rodríguez Pazos, Laura
Ginarte Val, Manuel Javier
Toribio Pérez, Jaime
Salas Ellacuriaga, Antonio
Vega Gliemmo, Ana
author_role author
author2 Rodríguez Pazos, Laura
Ginarte Val, Manuel Javier
Toribio Pérez, Jaime
Salas Ellacuriaga, Antonio
Vega Gliemmo, Ana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Founder Effect
Genes, Recessive
Haplotypes
Ichthyosis
Proteínas de Choque Térmico
Efecto Fundador
Genes Recesivos
Haplotipos
Ictiosis
topic Founder Effect
Genes, Recessive
Haplotypes
Ichthyosis
Proteínas de Choque Térmico
Efecto Fundador
Genes Recesivos
Haplotipos
Ictiosis
description Background: Mutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ~46%, ~21% and ~13% of all TGM1 gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region. Methodology/principal findings: In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the TGM1 gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry. Conclusions/significance: In good agreement with the documentation record and the census, both mutations arose between 2,800-2,900 years ago (y.a.), but their TMRCA was in the range 600-1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on TGM1 haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900-4,500 y.a. (95% highest posterior density) followed by exponential growth.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.11940/4880
url http://hdl.handle.net/20.500.11940/4880
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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