Exploring the Genetic Basis for Congenital Heart Disease with Mouse ENU Mutagenesis

Publisher Summary This chapter explores the genetic basis for congenital heart disease with the help of mouse ENU mutagenesis. The causes of congenital heart disease are complex (Strauss, 1998; Garg, 2006). A genetic contribution is clearly seen with chromosomal abnormalities such as in DiGeorge syndrome, where cardiac defects are found in conjunction with other birth defects due to haploinsufficiency associated with chromosome 22q11 microdeletion. Most human congenital heart diseases, however, are sporadic and nonsyndromic, occurring in isolation from other birth defects. Human congenital heart disease is often associated with variable penetrance, so that not all individuals with a disease-causing mutation will have the same structural heart disease. Variable expressivity is also observed, where the same mutation can present with different congenital heart disease in different patients. Finally, gene–environment interactions can affect disease risk, further complicating the analysis. The complex genetics associated with human congenital heart disease have been difficult to unravel, given the inherent genetic heterogeneity of the human population. This makes a compelling case for the use of genetically-inbred animal models to pursue studies to elucidate the genetic etiology of congenital heart disease.