Incorporating genetic analyses into birth defects cluster investigations: strategies for identifying candidate genes

Incorporating genetic analyses into birth defect cluster investigations may increase understanding of both genetic and environmental risk factors for the defect. Current constraints of most birth defect cluster investigations make candidate gene selection the most feasible approach. Here, we describe strategies for choosing candidate genes for such investigations, which will also be applicable to more general gene-environment studies.

We reviewed publicly available web-based resources for selection of candidate genes and identification of risk factors, as well as publications on different strategies for candidate gene selection.

Candidate gene selection requires consideration of available gene-disease databases, previous epidemiological studies, animal model research, linkage and expression studies, and other resources. We describe general considerations for utilizing available resources, as well as provide an example of a search for candidate genes related to gastroschisis.

Available web resources could facilitate selection of candidate genes, but selection of optimal candidates will still require a strong understanding of genetics and the pathogenesis of the defect, as well as careful consideration of previous epidemiological studies.