When the SCOR was renewed in 1995, the objectives were to identify polymorphisms in candidate genes and to use the polymorphisms for genetic association studies in patients. Subjects included those with Down syndrome and atrioventricular canal defects, non-Down subjects with atrioventricular canal defects, Down syndrome subjects with no functional heart disease, normal subjects with no heart disease or Down syndrome, Down syndrome subjects with perimembranous interventricular septal defects, and non-Down subjects with perimembranous interventricular septal defects. In addition, polymorphisms within candidate genes, as well as the highly polymorphic short tandem repeat polymorphisms (STRPs), were used in a genome-wide linkage search for the gene in large families with multiple affected individuals. When association or linkage studies suggested involvement of a specific gene, a search for mutations in the gene was carried out. In addition, the investigators determined whether a likely candidate chromosomal region (chromosome 21q21.1-qter) was involved in non-Downs AVCD by using molecular techniques to search for allele loss, uniparental disomy, and cryptic translocations. They also investigated the molecular genetic variability associated with endocardial cushion and ventricular septal development in Down syndrome subjects with and without heart disease and in normal subjects. Examinations were carried out in the relatives of these subjects to ascertain whether they had congenital heart defects or any other congenital anomalies. This was accomplished by obtaining family pedigrees, medical histories, and examining 1st degree relatives (and, if positive, 2nd and 3rd degree relatives) utilizing echocardiographic and electrocardiographic techniques.