Description) The current proposal is based on the premise that a full understanding of the genetic architecture for many birth defects will only be obtained if """"""""higher-order"""""""" effects such as gene-environment (GxE) interactions, gene-gene (GxG) interactions and maternal genotypic effects are evaluated in concert with more traditional epidemiological and genetic risk factors. Moreover, recent advances in molecular and statistical genetics provide a foundation upon which to build studies that address the role of higher-order effects, when such effects are suggested by current understanding of a disease's etiology. The investigators propose to evaluate the role of GxE interactions, GxG interactions and maternal effects in the etiology of two groups of birth defects: neural tube defects and cranial abnormalities including craniosynostosis and nonsynostotic posterior plagiocephaly (CSINSPP). These conditions were selected from other potential candidates because current understanding of their etiologies support multiple hypotheses regarding higher-order effects. Hence, for these conditions in particular, it is now feasible to begin to construct a multi- dimensional blueprint of their genetic architecture. They will use state-of- the-art genotyping methods, including high-throughput array technologies, and employ state-of-the-art statistical approaches to evaluate the role of higher- order effects in the etiology of spina bifida and CS/NSPP.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD039081-06
Application #
6786633
Study Section
Special Emphasis Panel (ZHD1-RRG-K (02))
Program Officer
Henken, Deborah B
Project Start
2000-09-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
6
Fiscal Year
2004
Total Cost
$454,674
Indirect Cost
Name
Texas A&M University
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
141582986
City
College Station
State
TX
Country
United States
Zip Code
77845
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Brown, Karen S; Huang, Yuehua; Lu, Zhi-Yong et al. (2006) Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells. Atherosclerosis 189:133-41
Jensen, Liselotte E; Hoess, Karen; Mitchell, Laura E et al. (2006) Loss of function polymorphisms in NAT1 protect against spina bifida. Hum Genet 120:52-7
Stanislawska-Sachadyn, Anna; Jensen, Liselotte E; Kealey, Carmel et al. (2006) Association between the NAT1 1095C > A polymorphism and homocysteine concentration. Am J Med Genet A 140:2374-7
Jensen, Liselotte E; Etheredge, Analee J; Brown, Karen S et al. (2006) Maternal genotype for the monocyte chemoattractant protein 1 A(-2518)G promoter polymorphism is associated with the risk of spina bifida in offspring. Am J Med Genet A 140:1114-8
Jensen, Liselotte E; Hoess, Katy; Whitehead, Alexander S et al. (2005) The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida. Birth Defects Res A Clin Mol Teratol 73:512-6
Rampersaud, E; Bassuk, A G; Enterline, D S et al. (2005) Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10. J Med Genet 42:940-6
Underkoffler, Lara A; Mitchell, Laura E; Abdulali, Zaki S et al. (2005) Transmission ratio distortion in offspring of mouse heterozygous carriers of a (7.18) Robertsonian translocation. Genetics 169:843-8
Etheredge, Analee J; Christensen, Kaare; Del Junco, Deborah et al. (2005) Evaluation of two methods for assessing gene-environment interactions using data from the Danish case-control study of facial clefts. Birth Defects Res A Clin Mol Teratol 73:541-6

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