International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 51 - SNP AND SSLP HAPLOTYPES, TUMOR MICROARRAYS, AND CONGENIC RECOMBINANTS IN THE IDENTIFICATION OF HCS7, A POTENT LIVER CANCER MODIFIER.

Bilger A, Schneider A, Leutkehoelter K, Sundlov T, Drinkwater N

University of Wisconsin Medical School, Madison, United States

The Hcs7 liver cancer modifier, which accounts for the majority of the high susceptibility of C3H mice relative to B6, lies in a 6.3 Mb region of distal Chromosome 1 (based on recombinant mapping).  This region is orthologous to regions of human chromosome 1q that are amplified in about half of liver and breast cancers.

  We have analyzed SSLP and SNP haplotypes, gene expression in normal and neoplastic tissue, and fine-structure recombinants to identify candidates for Hcs7.  For the haplotype analysis we analyzed 41 of the 114 known and predicted genes in the region for B6, C3H, and two additional strains, CBA and BR, whose sensitivity relative to B6 also maps to distal Chromosome 1.  Haplotypes were derived from ~102 kb of sequence from 260 exons and flanking introns, yielding 656 SNPs.  SSLP markers were chosen at 120 kb intervals.  The SNP and SSLP maps are remarkably similar, revealing the near-identity of B6 and BR throughout the region, as well as large blocks where the closely related CBA and C3H strains resemble or differ from each other.  This haplotype analysis, together with cDNA microarray analysis of expression in the tumors of sensitive and resistant congenic lines, has led us to focus on a small number of related genes that are candidates for Hcs7.

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