International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 11 - SEQUENCE AND HAPLOTYPE ANALYSIS OF H-RAS AND DISTAL CHROMOSOME 7 IN 12 MOUSE INBRED STRAINS REVEALS A STRONG ANCESTRAL BIAS

Drew JC, Kastenmeier AS, Drinkwater NR

McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, United States

Inbred mouse strains vary in the frequency of H-ras initiating mutations in chemically induced liver tumors.  To determine if allelic variation in the H-ras gene accounts for differences in mutant frequencies, we sequenced the 4.5kb H-ras gene from 14 inbred strains:  12 common laboratory strains (129P3/J, 129X1/SvJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57BR/cdJ, CBA/J, DBA/J, SM/J, and SWR/J) and 2 distant strains (CAST/Ei and SPRET/Ei).  Surprisingly, eleven inbred strains had identical sequences over the 4.5kb region.  The AKR/J strain exhibited 2 SNPs in non-coding regions signifying a remarkably low rate of polymorphism.  The genomes of common laboratory inbred strains are mosaics of M.m.domesticus and M.m.musculus sequence.  All 12 common inbred strains, including AKR/J, inherited H-ras alleles from M.m.domesticus.

To determine if the mono-allelism of H-ras is unique or represents a larger, selected region of distal Chr. 7, we sequenced 500-600 bp for each of 15 genes spanning the distal 10Mb for the 16 aforementioned strains.  In the 12 common inbred strains, an extremely low SNP rate (5.2x10-5) was observed for a 3-4 Mb interval including H-ras and Igf2, and the genes sampled in this sub-region share the M.m.domesticus allele.  This large block of mono-allelic genes is flanked by genomic regions with an over 60-fold higher SNP rate (3.3x10-3) and multiple archetypal haplotypes represented among 12 inbred strains. It is not known how common such stringently conserved haplotype blocks are in the genomes of the laboratory inbred strains. 

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