Abstract

As the human genome project progresses, the detailed structural information obtained will open up many opportunities for attacking significant biological problems that were impossible to study previously. We are interested in using the techniques of single molecule PCR to study the pattern of recombination along human chromosomes, and to study the rate of specific mutations which cause human disease in the male germ line. Using information on the physical distance between DNA polymorphisms, and the method of sperm typing, the patterns of recombination potential along a large chromosomal segment will be determined and the size of the chromosomal regions which have recombination hot spot activity will be accurately defined. The effect that structural rearrangements at the human MHC have on altering the patterns of genomic recombination will also be examined. Finally, methods to detect and quantify the level of specific mutations in the male germ line will be developed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM036745-08
Application #
3484845
Study Section
Genome Study Section (GNM)
Project Start
1985-09-01
Project End
1997-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Qin, Jian; Subramanian, Jaichandar; Arnheim, Norman (2009) Detection of meiotic DNA breaks in mouse testicular germ cells. Methods Mol Biol 557:165-81
Shelbourne, Peggy F; Keller-McGandy, Christine; Bi, Wenya Linda et al. (2007) Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum Mol Genet 16:1133-42
Wesoly, Joanna; Agarwal, Sheba; Sigurdsson, Stefan et al. (2006) Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol 26:976-89
Tiemann-Boege, Irene; Calabrese, Peter; Cochran, David M et al. (2006) High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing. PLoS Genet 2:e70
Wyrobek, A J; Eskenazi, B; Young, S et al. (2006) Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci U S A 103:9601-6
Subramanian, Jaichandar; Vijayakumar, Sangeetha; Tomkinson, Alan E et al. (2005) Genetic instability induced by overexpression of DNA ligase I in budding yeast. Genetics 171:427-41
Qin, Jian; Richardson, Laura L; Jasin, Maria et al. (2004) Mouse strains with an active H2-Ea meiotic recombination hot spot exhibit increased levels of H2-Ea-specific DNA breaks in testicular germ cells. Mol Cell Biol 24:1655-66
Pathak, S; Choi, S K; Arnheim, N et al. (2001) Hydroxylated quantum dots as luminescent probes for in situ hybridization. J Am Chem Soc 123:4103-4
Guan, T; Kehlenbach, R H; Schirmer, E C et al. (2000) Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol Cell Biol 20:5619-30
Lien, S; Szyda, J; Schechinger, B et al. (2000) Evidence for heterogeneity in recombination in the human pseudoautosomal region: high resolution analysis by sperm typing and radiation-hybrid mapping. Am J Hum Genet 66:557-66

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