The long-term objective of this research is a determination of the nature, causes, and effects of chromosomal mutations in mammals. Using natural populations of deer mice, we propose to generate data critical to understanding the genetics and organismal significance of chromosomal fragile sites and to continue our productive research into the details of the meiotic mechanisms which govern the process of chromosomal reorganization in mammals. Although the discovery of the human Fragile-X Syndrome (the second-most common chromosomal abnormality among the mentally retarded) has caused chromosomal fragile sites to become a major focus of clinical cytogenetics, next to nothing is known about the basic significance or genetic origin of these critical chromosomal regions. No animal model has been developed for investigations of fragile sites and few non-human species have even been surveyed for the occurrence of fragile sites. with he continued development of a deer mouse model for studying fragile sites, we propose to develop a statistical model which is appropriate for discretely identifying fragile sites from individuals and to test the hypothesis that common fragile sites represent heritable genetic loci at which chromosomal mutations are most likely to occur. We will examine the intraspecific variation of fragile sites and the degree to which fragile sites are conserved among species of known genetic relationships. Additionally, we propose to use techniques of somatic and meiotic karyology and electron microscopic analyses of synaptonemal complexes, to continue to rest the hypothesis that sex heterochromatin represents an unrecognized category of chromatin that regularly experiences unequal crossing over and that this phenomenon accounts for the various unusual but asymptomatic sex chromosomal conditions in deer mice. In particular we propose to test the hypothesis that the homogametic nature of the female sex chromosomes limits the source of sex-chromosomal recombination to the euchromatic portions of the X chromosomes, that females do not experience the unequal crossing over of sex heterochromatin which we have documented for males, and that the source of the sex heterochromatin variability is therefore limited to the male meiotic process.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM027014-14
Application #
2174868
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-03-01
Project End
1997-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
14
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
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Bohm, U; Dahm, P F; McAllister, B F et al. (1995) Identifying chromosomal fragile sites from individuals: a multinomial statistical model. Hum Genet 95:249-56

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