A YAC CONTIG SPANNING THE ATAXIA-TELANGIECTASIA LOCUS (GROUP-A AND GROUP-C) AT 11Q22-Q23

Ataxia-telangiectasia (A-T) is an autosomal recessive disease involvin g cerebellar degeneration, immunodeficiency, cancer predisposition, ch romosomal instability and radiosensitivity. A-T is heterogeneous, and the majority of A-T cases are associated with two complementation grou ps, A and C. The ATA and ATC loci are closely linked at chromosome 11q 22-q23. Recombination mapping and linkage disequilibrium analysis have confined both loci between the markers D11S1817 and D11S927, spaced a pproximately 3.5 Mb apart. Isolation in yeast artificial chromosomes o f the genomic segment defined by these loci is essential to identify t he gene or genes containing the ATA and ATC mutations. A YAC contig sp anning 4.5 Mb, which includes the D11S1817-D11S927 interval, was const ructed using two whole genome libraries (ICRF and St. Louis), and a ch romosome 11-specific library. Construction of this contig was expedite d by prior generation of a region-specific ICRF sublibrary using ALu-P CR products derived from a radiation hybrid. The contig was expanded f urther by screening the libraries with ALu-PCR products derived from Y AC clones and with STSs from YAC ends. YAC clones were aligned by fing erprinting with moderately repetitive probes. (C) 1994 Academic Press, Inc.