A tau haplotype is a variant form of the proximal portion of mouse chromosome 17 that has evolved the ability to propagate itself at the expense of wild-type meiotic partners. Males that are heterozygous for a tau haplotype can transmit it as an intact genetic unit to 95% or more of their off spring. This phenotype, known as transmission ration distortion (TRD), results from the genetic interaction of a series of tau-specific alleles at loci distributed along the 15 cM region of a tau haplotype. Two types of TRD loci have been defined. One is the tau complex responder (Tcr) locus which acts in a haploid-specific manner to determine which homolog of chromosome 17 will be transmitted at a high ratio. The second is the class tau complex disorder (Tcd) loci which can act in cis or trans configuration to Tcr and are defined by their ability to control the absolute level at which transmission ratios are distorted. The goal of the first three specific aims of this proposal is an increased understanding of the TRD phenotype and tau haplotype effects on sperm function. In particular, the first specific aim is directed toward a further analysis of the expression & function of a recently-cloned gene family that includes a strong candidate for the Tcr locus. Three types of experiments are proposed: (1) PCR analysis of patterns of expression and transcript processing during sequential stages of haploid germ cell differentiation; (2) transgenic studies of the functionality of the candidate Tcr gene; and (3) analysis of polypeptide products from the candidate Tcr gene. The second specific aim is directed toward studies of the Tcd loci. Experiments similar to those described above will be performed on a cloned candidate for one of the Tcd loci, and additional Tcd loci will be cloned based on the genetics and molecular biology of the tau system. The third specific aim is directed toward a genetic analysis of a tau haplotype-induced sterility phenotype. Finally, the goal of the fourth specific aim is a better understanding of the evolutionary history of tau haplotypes. This will be accomplished through the construction of phylogenetic trees (by a maximum parsimony algorithm) for loci distributes along the tau region. The ultimate objective of the research described in this proposal is to use the tau haplotype system as a vehicle with which to gain insight towards (1) general principles of germ cell differentiation & the role played in this process by haploid gene expression, and (2) general principles of chromosomal evolution in mice.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020275-11
Application #
2197983
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1984-09-30
Project End
1995-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Harrelson, Zachary; Kelly, Robert G; Goldin, Sarah N et al. (2004) Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development 131:5041-52
Mahadevan, Navin R; Horton, Amy C; Gibson-Brown, Jeremy J (2004) Developmental expression of the amphioxus Tbx1/ 10 gene illuminates the evolution of vertebrate branchial arches and sclerotome. Dev Genes Evol 214:559-66
Horton, Amy C; Gibson-Brown, Jeremy J (2002) Evolution of developmental functions by the Eomesodermin, T-brain-1, Tbx21 subfamily of T-box genes: insights from amphioxus. J Exp Zool 294:112-21
Ruvinsky, Ilya; Chertkov, Olga; Borue, Xenia V et al. (2002) Genetics analysis of mouse mutations Abnormal feet and tail and rough coat, which cause developmental abnormalities and alopecia. Mamm Genome 13:675-9
Ahn, D G; Ruvinsky, I; Oates, A C et al. (2000) tbx20, a new vertebrate T-box gene expressed in the cranial motor neurons and developing cardiovascular structures in zebrafish. Mech Dev 95:253-8
Ruvinsky, I; Oates, A C; Silver, L M et al. (2000) The evolution of paired appendages in vertebrates: T-box genes in the zebrafish. Dev Genes Evol 210:82-91
Ruvinsky, I; Gibson-Brown, J J (2000) Genetic and developmental bases of serial homology in vertebrate limb evolution. Development 127:5233-44
Ruvinsky, I; Silver, L M; Gibson-Brown, J J (2000) Phylogenetic analysis of T-Box genes demonstrates the importance of amphioxus for understanding evolution of the vertebrate genome. Genetics 156:1249-57
Hancock, S N; Agulnik, S I; Silver, L M et al. (1999) Mapping and expression analysis of the mouse ortholog of Xenopus Eomesodermin. Mech Dev 81:205-8
Law, D J; Garvey, N; Agulnik, S I et al. (1998) TBX10, a member of the Tbx1-subfamily of conserved developmental genes, is located at human chromosome 11q13 and proximal mouse chromosome 19. Mamm Genome 9:397-9

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