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Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci

BACKGROUND: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular...

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Autores principales: Flaquer, Antònia, Baumbach, Clemens, Piñero, Estefania, García Algas, Fernando, de la Fuente Sanchez, María Angeles, Rosell, Jordi, Toquero, Jorge, Alonso-Pulpon, Luis, Garcia-Pavia, Pablo, Strauch, Konstantin, Heine-Suñer, Damian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664624/
https://www.ncbi.nlm.nih.gov/pubmed/23705960
http://dx.doi.org/10.1186/1471-2156-14-44
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author Flaquer, Antònia
Baumbach, Clemens
Piñero, Estefania
García Algas, Fernando
de la Fuente Sanchez, María Angeles
Rosell, Jordi
Toquero, Jorge
Alonso-Pulpon, Luis
Garcia-Pavia, Pablo
Strauch, Konstantin
Heine-Suñer, Damian
author_facet Flaquer, Antònia
Baumbach, Clemens
Piñero, Estefania
García Algas, Fernando
de la Fuente Sanchez, María Angeles
Rosell, Jordi
Toquero, Jorge
Alonso-Pulpon, Luis
Garcia-Pavia, Pablo
Strauch, Konstantin
Heine-Suñer, Damian
author_sort Flaquer, Antònia
collection PubMed
description BACKGROUND: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects — for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. RESULTS: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P(empirical) = 0.0004) and at chromosome 18 (18q21.2, P(empirical) = 0.0005). CONCLUSIONS: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD.
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spelling pubmed-36646242013-05-28 Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci Flaquer, Antònia Baumbach, Clemens Piñero, Estefania García Algas, Fernando de la Fuente Sanchez, María Angeles Rosell, Jordi Toquero, Jorge Alonso-Pulpon, Luis Garcia-Pavia, Pablo Strauch, Konstantin Heine-Suñer, Damian BMC Genet Research Article BACKGROUND: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects — for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. RESULTS: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P(empirical) = 0.0004) and at chromosome 18 (18q21.2, P(empirical) = 0.0005). CONCLUSIONS: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD. BioMed Central 2013-05-24 /pmc/articles/PMC3664624/ /pubmed/23705960 http://dx.doi.org/10.1186/1471-2156-14-44 Text en Copyright © 2013 Flaquer et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Flaquer, Antònia
Baumbach, Clemens
Piñero, Estefania
García Algas, Fernando
de la Fuente Sanchez, María Angeles
Rosell, Jordi
Toquero, Jorge
Alonso-Pulpon, Luis
Garcia-Pavia, Pablo
Strauch, Konstantin
Heine-Suñer, Damian
Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title_full Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title_fullStr Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title_full_unstemmed Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title_short Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci
title_sort genome-wide linkage analysis of congenital heart defects using mod score analysis identifies two novel loci
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664624/
https://www.ncbi.nlm.nih.gov/pubmed/23705960
http://dx.doi.org/10.1186/1471-2156-14-44
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