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Principal Investigator: Dr. Paula Cohen
Contact Information: E-mail: pc242@cornell.edu - Phone: 607-253-4301
Sponsor: March of Dimes Birth Defects Foundation
Grant Number: 1-FY06-373
Title: Elucidating the Functional Relationship Between NEK1 and FKBP6 in Mammalian Meiosis
Annual Direct Cost: $68,210
Project Period: 06/01/06-05/31/09
DESCRIPTION (provided by applicant): As described above, aneuploidy accounts for over 25% of human miscarriages and is the leading cause of mental retardation in live births. Approximately 0.3% of newborns are chromosomally aneuploid, with most of these exhibiting trisomy of chromosome 21 or of the sex chromosomes3. Clearly, therefore, the cost of such errors to human health is significant, and makes the study of mammalian meiosis all the more critical. Furthermore, the discrepancy in error rates between male and female meiosis (1% compared to 20-30%, respectively) enforces the need to study such events in mammals and, more importantly, to combine studies of male meiosis with that of female meiosis. The ultimate goal of such comparative analysis is the identification of regulatory events that may differ between the sexes and that may pinpoint the divergence point in terms of meiotic stringency between male and female meiocytes. The studies outlined in the current proposal seek to address such issues by exploring the regulatory aspects of mammalian meiosis that involve tying recombination and synapsis events to those events surrounding cell cycle control and by comparing such processes in both sexes. It is the cell cycle and checkpoint monitoring events that appear to hold the key to the sexual dimorphism in mammalian meiosis and therefore these studies will also tackle the important questions relating to male/female difference in mammalian meiosis. An example of this difference is highlighted most dramatically in the sex differences observed in Fkbp6 mutant mice coupled with the similar meiotic phenotypes (though perhaps less drastic in females) in male and female Nek1kat/kat mice.
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