The genes of the human leukocyte antigen (HLA) region control a variety Of functions involved in the immune response, and influence susceptibility to over 40 diseases. Our understanding of the structure and function of the HLA genes, their disease associations, and the evolutionary features of this multigene family has benefitted from recent advances in molecular biology, immunology, disease modelling and population genetics. Theoretical studies in the development of models to determine the modes of inheritance of the HLA associated diseases have led to a better understanding of the inheritance patterns in insulin dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic components.
The specific aims of our research are to study the genetic components in the etiology of the HLA associated diseases, and population genetic features of the HLA system. A variety of methods to test modes of inheritance of diseases using marker allele information, will be developed. Methods appropriate for the analysis of marker systems which are not highly polymorphic, to both detect linkage and determine modes of inheritance, will be investigated. The information content of particular pedigree types for LOD score analysis will be investigated. Two methods using patterns of linkage disequilibrium will be investigated to determine their usefulness in mapping disease predisposing genes. A number of large collaborative data sets of HLA associated diseases will be analyzed. A framework for genetic counselling of HLA associated, and other complex diseases, will be developed. The results of our studies are generally applicable to the mapping and characterization of complex human genetic traits.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD012731-15
Application #
3311999
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1979-04-01
Project End
1997-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
15
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Grote, M N; Klitz, W; Thomson, G (1998) Constrained disequilibrium values and hitchhiking in a three-locus system. Genetics 150:1295-307
Valdes, A M; Thomson, G (1997) Detecting disease-predisposing variants: the haplotype method. Am J Hum Genet 60:703-16
Valdes, A M; McWeeney, S; Thomson, G (1997) HLA class II DR-DQ amino acids and insulin-dependent diabetes mellitus: application of the haplotype method. Am J Hum Genet 60:717-28
Bui, M M; Luo, D F; She, J Y et al. (1996) Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas. J Autoimmun 9:97-103
Luo, D F; Buzzetti, R; Rotter, J I et al. (1996) Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum Mol Genet 5:693-8
Salamon, H; Tarhio, J; Ronningen, K et al. (1996) On distinguishing unique combinations in biological sequences. J Comput Biol 3:407-23
Field, L L; Tobias, R; Thomson, G et al. (1996) Susceptibility to insulin-dependent diabetes mellitus maps to a locus (IDDM11) on human chromosome 14q24.3-q31. Genomics 33:1-8
Luo, D F; Bui, M M; Muir, A et al. (1995) Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27. Am J Hum Genet 57:911-9
Thomson, G (1995) Mapping disease genes: family-based association studies. Am J Hum Genet 57:487-98
Thomson, G (1995) Analysis of complex human genetic traits: an ordered-notation method and new tests for mode of inheritance. Am J Hum Genet 57:474-86

Showing the most recent 10 out of 66 publications