The overall objective is to understand the genetics and genetic regulation of the Qa antigens encoded by the murine major histocompatibility complex. This complex has been a major concern to immunogeneticists for many years, initially because of its influence on tissue transplantation and more recently because of its involvement in determining the susceptibility to viral infections and successful cell-cell interactions during an immune response. The function of the Qa antigens and molecules has not been clearly defined although their unusual appearance on certain leukemia cells raises the possibility that they are involved in a normal or abnormal differentiation process. In this proposal, there are four specific aims: (1) to examine the allelism and polymorphism of genes within the Q subregion; (2) to determine the sites of recombination within and/or adjacent to the Q subregion, (3) to analyze the transcription and translation of Q subregions genes and (4) to study the control of the quantitative control of Q subregion gene products. Techniques to be used include molecular cloning and subcloning, isolation of genomic DNA and mRNA, Southern and Northern blot analyses, in vitro transcription and translation system, DNA mediated gene transfer, and DNA sequencing.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037947-05
Application #
3293826
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-07-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
110521739
City
Menands
State
NY
Country
United States
Zip Code
12204
Flaherty, L; Bryda, E C; Collins, D et al. (1995) New mouse model for polycystic kidney disease with both recessive and dominant gene effects. Kidney Int 47:552-8
Montgomery, J C; Guarnieri, M H; Tartaglia, K E et al. (1994) High-resolution genetic map and YAC contig around the mouse neurological locus reeler. Mamm Genome 5:756-61
Rinchik, E M; Flaherty, L; Russell, L B (1993) High-frequency induction of chromosomal rearrangements in mouse germ cells by the chemotherapeutic agent chlorambucil. Bioessays 15:831-6
Wade, N; Flaherty, L (1993) DNA sequence analysis and polymorphism of the mouse CD4 gene. Immunogenetics 38:384
Flaherty, L; Messer, A; Russell, L B et al. (1992) Chlorambucil-induced mutations in mice recovered in homozygotes. Proc Natl Acad Sci U S A 89:2859-63
Tine, J A; Walsh, A; Rathbun, D et al. (1990) Genetic polymorphisms of Q region genes from wild-derived mice: implications for Q region evolution. Immunogenetics 31:315-25
Flaherty, L; Elliott, E; Tine, J A et al. (1990) Immunogenetics of the Q and TL regions of the mouse. Crit Rev Immunol 10:131-75
Elliott, E; Rathbun, D; Ramsingh, A et al. (1989) Genetics and expression of the Q6 and Q8 genes. An LTR-like sequence in the 3' untranslated region. Immunogenetics 29:371-9
Flaherty, L (1988) Major histocompatibility complex polymorphism: a nonimmune theory for selection. Hum Immunol 21:3-13
Elliott, E; Karl, M; Flaherty, L (1987) Novel mRNA species from a Q-subregion class-I gene of the murine major histocompatibility complex. Gene 61:189-98

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