The goal of this research is to apply a newly developed research design to search for quantitative trait loci (QTL's) that contribute to genetic variation in birth weight, body size and adolescent growth, and to determine whether any of the QTL's that are detected, are influenced by genomic imprinting. DNA samples will be obtained from 600 monozygotic (MZ) and dizygotic (DZ) twins and their parents and typed for 225 polymorphic markers spaced at approximately 15 cM intervals throughout the genome. Using the parental typing data, the DZ pairs will be classified into four groups according to the alleles they share that are identical by descent (IBD) at each marker locus and compared with MZ pairs who share two alleles IBD at the marker and at all other loci as well. Quantitative genetic analysis of the resulting data will permit estimation of the total genetic variation in the phenotype as well as the proposition attributable to any closely linked QTL and imprinting effects of the QTL respectively. The search will begin with 10 selected candidate loci including INS, IGF1, IGF2, IGF1R, IGF2R, GH1, GH2, GHR, GHRF and SNRPN. The resulting IBD scored twin sample will be an enormously valuable resource which could be used to search for QTL's that influence ANY heritable quantitative trait. Extensive longitudinal data are already available in this population on multiple anthropometric, cardiovascular and biochemical variables which will be subjected to these analyses.
