Large scale duplication, from chromosomal fragments to the entire genome, followed by mutation is considered a major force driving functional diversity in vertebrates. Isolated examples of duplicated regions support this theory, but a genome-wide study of mammalian gene duplication and subsequent functional diversification has not been attempted. A better understanding of the functional similarities between duplicated genes would greatly enhance the power of paralogous relationships in predicting gene function and understanding genetic disease. The candidate's long-term career goal is to establish an independent, research program in academia, using computational genomics to study the role of gene duplication in the evolution, structure and function of mammalian genomes. The specific goals of the current proposal constitute the first step in this program and will allow the candidate to demonstrate the feasibility of her interdisciplinary approach. They are (1) to construct a spatially ordered set of all discernible duplicated genes in the mouse and human genomes and to estimate the time of duplication for each; (2) to develop algorithms to identify the number of large scale duplications that took place and determine the sequence of rearrangements that subsequently fragmented them; (3) to determine, using probabilistic models of rearrangements, to what extent spatial organization of duplicated regions is preserved; and (4) to annotate the duplication data with functional data in preparation for studying the processes of functional differentiation following duplication.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Career Transition Award (K22)
Project #
5K22HG002451-03
Application #
6616713
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Graham, Bettie
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
3
Fiscal Year
2003
Total Cost
$262,970
Indirect Cost
Name
Carnegie-Mellon University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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