Abstract

The proposed studies are designed to provide a molecular analysis of structure, organization and polymorphisms of genes within the major histocompatibility complex (MHC) on the short arm of human chromosome six (6p). The definition of functional domains and post synthetic modifications as revealed in primary structure of the MHC class III gene products will be elucidated. The findings from these two groups of studies will be applied to define molecular markers for the analysis of linkage to human congenital/genetic diseases such as 21 hydroxylase deficiency, cleft lip, neural tube defects, gluten sensitive enteropathy and deficiency of one of the class III proteins. Modern tools of molecular genetics, protein biosynthesis and protein chemistry will be applied to the study of patients, their families and normal families with informative markers on 6p. The overall objectives are to understand the basis for 6p linked diseases, and to find predictive independent markers for these disorders. Thus more effective and comprehensive genetic counselling might result.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD017461-05
Application #
3096827
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1983-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Szilagyi, Agnes; Banlaki, Zsofia; Pozsonyi, Eva et al. (2010) Frequent occurrence of conserved extended haplotypes (CEHs) in two Caucasian populations. Mol Immunol 47:1899-904
Johnson, B A; Geha, M; Blackwell, T K (2000) Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival. Oncogene 19:1657-64
Libert, C; Wielockx, B; Grijalba, B et al. (1999) The role of complement activation in tumour necrosis factor-induced lethal hepatitis. Cytokine 11:617-25
Circolo, A; Garnier, G; Fukuda, W et al. (1999) Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology 42:135-49
Lokki, M L; Circolo, A; Ahokas, P et al. (1999) Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. J Immunol 162:3687-93
De, J; Lai, W S; Thorn, J M et al. (1999) Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression. Gene 228:133-45
Hausmann, S; Biddison, W E; Smith, K J et al. (1999) Peptide recognition by two HLA-A2/Tax11-19-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures. J Immunol 162:5389-97
Wang, X; Circolo, A; Lokki, M L et al. (1998) Molecular heterogeneity in deficiency of complement protein C2 type I. Immunology 93:184-91
Gauthier, L; Smith, K J; Pyrdol, J et al. (1998) Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein. Proc Natl Acad Sci U S A 95:11828-33
Tsitsikov, E N; Gutierrez-Ramos, J C; Geha, R S (1997) Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc Natl Acad Sci U S A 94:10844-9

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