Abstract

Novel Approaches to Studying Mammalian Hot Spots of Recombination 1. We will continue our analysis of the molecular nature of the recombination hot spot found in the human beta globin gene complex and initiate studies on the hot spot found in the mouse immune response region using our yeast meiosis system. The goal of these investigations is to define the molecular nature of recombination hot spots at the nucleic acid level. 2. Applying a novel technology we recently developed for enzymatically amplifying DNA sequences we aim to determine the restriction fragment length polymorphism genotype of single sperm cells (haplotype determination) at the DNA level. The analysis of thousands of individual sperm using this system will allow us to study the actual frequency of recombination between very closely linked RFLPs without family studies and can be used to directly study human recombination hot spots as well as to derive accurate genetic maps over very short distances.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM036745-05
Application #
3291220
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1985-09-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1990
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

Eboreime, Jordan; Choi, Soo-Kung; Yoon, Song-Ro et al. (2016) Estimating Exceptionally Rare Germline and Somatic Mutation Frequencies via Next Generation Sequencing. PLoS One 11:e0158340
Arnheim, Norman; Calabrese, Peter (2016) Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers. Annu Rev Genomics Hum Genet 17:219-43
Fischer, Jared M; Calabrese, Peter P; Miller, Ashleigh J et al. (2016) Single cell lineage tracing reveals a role for Tgf?R2 in intestinal stem cell dynamics and differentiation. Proc Natl Acad Sci U S A 113:12192-12197
Yoon, Song-Ro; Choi, Soo-Kung; Eboreime, Jordan et al. (2013) Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. Am J Hum Genet 92:917-26
Shinde, Deepali N; Elmer, Dominik P; Calabrese, Peter et al. (2013) New evidence for positive selection helps explain the paternal age effect observed in achondroplasia. Hum Mol Genet 22:4117-26
Choi, Soo-Kyung; Yoon, Song-Ro; Calabrese, Peter et al. (2012) Positive selection for new disease mutations in the human germline: evidence from the heritable cancer syndrome multiple endocrine neoplasia type 2B. PLoS Genet 8:e1002420
Qin, Jian; Subramanian, Jaichandar; Arnheim, Norman (2009) Detection of meiotic DNA breaks in mouse testicular germ cells. Methods Mol Biol 557:165-81
Yoon, Song-Ro; Qin, Jian; Glaser, Rivka L et al. (2009) The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect. PLoS Genet 5:e1000558
Arnheim, Norman; Calabrese, Peter (2009) Understanding what determines the frequency and pattern of human germline mutations. Nat Rev Genet 10:478-88
Tiemann-Boege, Irene; Curtis, Christina; Shinde, Deepali N et al. (2009) Product length, dye choice, and detection chemistry in the bead-emulsion amplification of millions of single DNA molecules in parallel. Anal Chem 81:5770-6

Showing the most recent 10 out of 46 publications