International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Sunday 17 November

14:15 - 14:30 HRS

COMPARATIVE SEQUENCE ANALYSIS OF 3.6 MB OF THE MOUSE AND HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

A. Kumánovics
University of Texas Southwestern Medical Center

Co-Authors: 2) Takada T, 1) Jones EP, 2) Fischer Lindahl K
Institutions: 1) University of Texas Southwestern Medical Center, 2) Howard Hughes Medical Institute and University of Texas Southwestern Medical Center

We are finishing the sequence of the 129/SvJ mouse Mhc (or H2) class I region on Chr 17 and the human sequence is already completed. Here we present a large-scale comparison of the Mhc from the two species to define the limits of mouse as model organism and to understand the evolution of the Mhc. We describe differences at the level of (1) genomic organization, (2) orthologous and paralogous gene families, (3) single gene insertions and deletions, and (4) gene structure. The only major organizational difference between the rodent and human Mhc is the presence of a 45 kb insert with class I genes in the proximal part of the mouse Mhc. The orthology between the central 1 Mb of the human and mouse Mhc is long established. Our sequencing extends this to the distal ~2 Mb region. The Mhc is a mosaic of stretches formed by conserved and non-conserved genes. Surprisingly, the ~1.9 Mb stretches that encode the class I and class II genes, which epitomize the Mhc, are the least conserved part, whereas the ~1.7 Mb stretches that encode at least 115 other genes are highly conserved. In the conserved regions, the synteny might be interrupted by gene insertions, and some of the orthologous proteins lost domains. The non-conserved parts can differ significantly in size and gene content: e.g., the mouse M1/M10 region is 580 kb and encodes 9 functional genes, whereas the corresponding human region is 106 kb and contains only 1 pseudogene.


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