Project: Research project

Project Details


The long term objective of the proposed studies is to define the
relationship between diversity of structure in MHC genes and the function
of those genes in the immune system. The significance of these studies
stems from the fact that our understanding of the role of MHC genes in
immune function is largely derived from analyses based on polymorphisms
defined in inbred mice. Since these structurally relevant polymorphisms
influence function of the MHC products, it is of great interest to define
which polymorphisms are relevant to the diversification of alleles within
inbreeding populations and which are representative of individuals from
genetically isolated populations. The specific aims are: 1) To
characterize a unique MHC haplotype by comparison with two other previously
described haplotypes defining features of haplotype variation that are
relevant to MHC function and evolution. 2) To determine if haplotypes
other than H-2b undergo copy events that lead to diversification of gene
encoding antigen presenting products of the class I and class II regions of
the H-2 complex. 3) To define the relative contributions of spontaneous
point mutations and copy mediated mutations in the diversification and
polymorphism of MHC genes. The analyses will be accomplished by the
molecular genetic comparison of cloned genes among genetically defined
mouse strains. Cosmid and phage genomic libraries of A.CA, B10.M, C57BL/6
and C57BL/10 lines will be analyzed to isolate homologous class I and class
II sequences. Comparative studies will be based on restriction
endonuclease mapping and DNA sequence analyses of genes derived from each
library. Synthetic oligonucleotide probes will be used to identify
specific DNA sequences that are shared by MHC genes within and among the
H-2f and H-2b haplotypes. Direct DNA sequence analysis of homologous
portions of MHC genes will provide estimates of spontaneous mutation and
copy mediated mutation rates as well as provide data pertaining to the
number of generations the various haplotypes that have been used to define
MHC variation have diverged from each other.
Effective start/end date7/1/858/31/97


  • Medicine(all)
  • Immunology and Microbiology(all)