3. Sequencing Human Chromosome 14 and the Mouse Major Histocompatibility Locus: A Progress Report 

Lee Rowen, Anup Madan, Shizhen Qin, Lee Hood, and the Multimegabase Sequencing Group Department of Molecular Biotechnology, University of Washington, Seattle, Washington 
leerowen@u.washington.edu 

To date, we have sequenced over 1.1 megabases of the mouse major histocompatibility locus and over 600 kb of chromosome 14. Our target region on chromosome 14 is 14q24.3-ter. 

Based on a preliminary analysis of the mouse MHC sequences, and a comparison with the human sequence counterpart, we have drawn the following conclusions: 

1) Evolutionarily conserved genes are interspersed with genes with no identifiable homologues in other species, suggesting that genes with both specialized and generalized (housekeeping) functions co-exist in the MHC. 

2) The MHC class III region is the most gene-dense. In the human sequence, 17% of 263 kb contains the coding region of 20 genes (average of 1 gene per 13.2 kb). The average intergenic distance is 2.7 kb. 

3) Expansion of gene family membership has occurred through the duplication of long repeats. 

4) Gene content and order in human and mouse MHC is similar, although variation in the extent of gene duplication occurs both within and between species. 

5) Conserved blocks between human and mouse correspond to the most gene-dense regions in each specie. 

6) Isochore boundaries, based on GC content and genome-wide interspersed repeats, can be identified in the class II-III regions in both species.