Genetic linkage maps of human chromosomes are important tools for the initial localization of disease genes. Although numerous linkage maps of human chromosomes have been published and many disease genes have been mapped, the localization of additional disease genes would be facilitated if the existing maps were improved. Three characteristics of the markers used to build linkage maps which need to be improved are a) informativeness, as measured by PIC or heterozygosity; b) spacing, as measured by the average and maximum separations between adjacent markers in cM; and c) ease of use, with markers typable by PCR generally preferred over those which require Southern blotting. The index map project funded by the NCHGR is making progress towards these goals, with the construction of maps of markers that have minimum heterozygosities of 70% with marker spacing such that gaps do not exceed 10-15 cM. However, it is desirable and feasible to extend the resolution of the index maps to 2-5 cM, which would greatly facilitate the fine mapping of disease genes. The overall goal of this grant is to construct a high resolution linkage map of human chromosome 11. This map will consist of """"""""supermarkers"""""""", i.e., microsatellite markers with minimum heterozygosities of 70%, spaced at intervals (on the sex-average map) averaging 2 cM with no gaps exceeding 5 cM. This linkage mapping effort will be closely coordinated with the physical mapping of chromosome 11 that is presently ongoing in glen Evans' lab. To reach this overall goal, the following specific aims are proposed: (1.) To assign existing supermarkers to cosmid clones from the Evans' labs chromosome 11 specific libraries and, where necessary, to add them to the linkage map of the chromosome. Using the index map as a framework, new markers will be added using an efficient meiotic mapping panel approach. (2.) To develop new supermarkers from cosmids or YACs that have been localized to regions of chromosome 11 corresponding to gaps in the high resolution map. (3.) To add the new markers to the linkage map of the chromosome and to compare the marker orders (and map distances) deduced from this linkage map with those deduced from the physical map. A subsidiary, but important, goal is to construct a """"""""user-friendly"""""""" set of index markers from chromosome 11 that can be typed by multiplex utilizing a single electrophoretic gel run.
| Litt, M; Carrero-Valenzuela, R; LaMorticella, D M et al. (1997) Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet 6:665-8 |
| Caryyro-Valenzuela, R; Lindblad, K; Payami, H et al. (1995) No evidence for association of familial Parkinson's disease with CAG repeat expansion. Neurology 45:1760-3 |
