Mapping Human Genomic Regions Identical by Descent

We will develop methods that will permit the application of genomic mismatch scanning (GMS) to thegenome. If GMS can be applied to humans, it will rapidly identify the sub-chromosomal locations of cdisorders, such as non-insulin dependent diabetes mellitus, facilitating the subsequent isolation ofuse resources that are currently in house including a hybrid cell line, a set of yeast artificial chDNA from members of a large family segregating maturity-onset diabetes of the young (MODY) which mapchromosome 20q12-q13.1. To reduce the complexity of the starting DNA, PCR primers that are homologourepetitive elements will be used to amplify the DNA between repeats. Methods that favor the amplificfragments will be applied. Alu PCR will be performed on a chromosome 20 monochromosomal hybrid cellamplified products will be used to work out conditions for the formation of DNA hybrids and mismatchMutHLS proteins. The hybrid molecules that remain will be radiolabeled and hybridized to dot blots oq13.1 YAC DNA and high density grids of DNA from the CEPH mega YAC library. Once conditions are deteresult in the identification of chromosome 20 YACs using the chromosome 20 hybrid cell line, these tapplied to several pairs of affected relatives in the MODY pedigree that share a chromosome 20q12q13Hybrids generated from each affected pair by GMS will be radiolabeled and hybridized to the YAC blotof the positive YACs will be identified. Positive YACs from each GMS selected pair will be comparedgenomic regions are shared by all affected pairs.