Abstract

Compared to the general population, individuals with Down syndrome (DS) are at a 500-fold increased risk for complete atrioventricular septal defects (AVSDs), a severe form of congenital heart defect (CHD) that significantly impacts morbidity and mortality in this population. The purpose of this study is to identify environmental exposures and genetic variants on chromosome 21 that contribute to CHD susceptibility using a candidate gene approach in a DS population with complete AVSDs. Specifically, 1) candidate genes within the 10Mb DS heart critical region will be prioritized by characterizing transcript expression in human fetal and adult heart tissue, 2) our current DS with AVSD population will be expanded to facilitate epidemiological and association studies, and 3) single nucleotide polymorphisms in candidate genes will be genotyped to conduct an association study utilizing statistical methods developed for use with trisomic populations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD046337-01
Application #
6741226
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Oster-Granite, Mary Lou
Project Start
2004-01-01
Project End
2006-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
1
Fiscal Year
2004
Total Cost
$46,420
Indirect Cost

  Institution

Name
Emory University
Department
Genetics
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Ackerman, Christine; Locke, Adam E; Feingold, Eleanor et al. (2012) An excess of deleterious variants in VEGF-A pathway genes in Down-syndrome-associated atrioventricular septal defects. Am J Hum Genet 91:646-59
Bean, Lora J H; Allen, Emily G; Tinker, Stuart W et al. (2011) Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project. Birth Defects Res A Clin Mol Teratol 91:885-93
Locke, Adam E; Dooley, Kenneth J; Tinker, Stuart W et al. (2010) Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome. Genet Epidemiol 34:613-23
Freeman, S B; Torfs, C P; Romitti, P A et al. (2009) Congenital gastrointestinal defects in Down syndrome: a report from the Atlanta and National Down Syndrome Projects. Clin Genet 75:180-4
Lin, Yan; Tseng, George C; Cheong, Soo Yeon et al. (2008) Smarter clustering methods for SNP genotype calling. Bioinformatics 24:2665-71
Freeman, Sallie B; Bean, Lora H; Allen, Emily G et al. (2008) Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project. Genet Med 10:173-80
Maslen, Cheryl L; Babcock, Darcie; Robinson, Susan W et al. (2006) CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal defects in Down syndrome. Am J Med Genet A 140:2501-5