International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

MONDAY OCTOBER 18

2.45pm – 3.00pm

THE FUNCTIONAL IMPLICATIONS OF LINKAGE DISEQUILIBRIUM BLOCKS ON MOUSE CHROMOSOMES

Paigen K, Petkov PM, Graber JH, Churchill G

The Jackson Laboratory, Bar Harbor, ME, United States

Typing 1508 SNPs chosen for high information content on 63 common and wild-derived mouse strains chosen for maximum genetic diversity, we find that over half the mouse genome presents as large blocks of linkage disequilibrium (LD blocks), averaging 5 Mb in length and 100 times the length of LD blocks typically observed in human studies.  The largest block, 40+ Mb, is on the X chromosome.  LD blocks can be segmented, containing short, internal regions in linkage equilibrium, and show internal haplotype switching.

  Strong LD does not result from a deficiency of recombining ability in these regions as their average cM/Mb is similar to the genome wide average; nor does it appear to derive from the common genetic origins of laboratory inbred mice as only 12-13% of unlinked genes show LD.  Rather, a compression of genetic distances in LD regions compared to non-LD regions among RI lines indicates that LD arises from convergent selection of co-adapted sets of alleles at functionally related linked genes during the intense reproductive selection applied during inbred strain formation, allied with the pressures of survival as homozygotes. 

  Importantly, some LD blocks form inter-connnected networks seen as LD between genetically unlinked blocks, presumably reflecting functional relationships of distant chromosome regions.

  To the extent ancient evolutionary forces have driven the arrangement of genes along mammalian chromosomes, putting functionally related genes in proximity to promote their common inheritance, observations of LD in inbred mice provide a means of investigating this functional organization.

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