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

BMC Genetics

Damian Heine-Suñer²  Konstantin Strauch⁵  Pablo Garcia-Pavia⁴  Luis Alonso-Pulpon⁴  Jorge Toquero⁴  Jordi Rosell²  María Angeles de la Fuente Sanchez³  Fernando García Algas³  Estefania Piñero¹  Clemens Baumbach⁵  Antònia Flaquer⁵ 

[1] Research Unit, Son Espases University Hospital, Palma de Mallorca, Spain;Genetic Section, Son Espases University Hospital, Palma de Mallorca, Spain;Pediatric Cardiology, Son Espases University Hospital, Palma de Mallorca, Spain;Cardiomyopathy Unit, Department of Cardiology, Puerta de Hierro University Hospital, Madrid, Spain;Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

关键词: Genome-wide study;    Linkage analysis;    Genetics;    Congenital heart defects;   

Others  :  1087051
DOI  :  10.1186/1471-2156-14-44

 received in 2013-02-06, accepted in 2013-05-16,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Flaquer et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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