Abstract

The objective of this research is to develop statistical methods to assess whether mitochondrial DNA (mtDNA) mutations are involved in the etiology of disease and to estimate the contribution of mtDNA mutations to the disease.
The specific aims are as follow: (1) to propose sampling schemes and test statistics to identify if mtDNA mutations are involved in a disease; to compare the power of the test statistics using different sampling schemes assuming mtDNA mutations are involved in the disease; (2) to study if mtDNA mutations are the primary cause of the disease or nuclear mutations may also be involved in the etiology of the disease; in the later case, study the interaction between mtDNA mutations and nuclear mutations; and (3) to estimate the contribution of mtDNA mutations to the disease. The test methods developed in this study will be evaluated and validated through simulation studies and will be applied to a collection of pedigrees for Leber's hereditary optic neuropathy (LHON), a disease known to be related to mtDNA mutations. The test methods and statistics will be applied to field studies on insulin-dependent diabetes mellitus (IDDM). Continuing collaborations on other complex diseases will be sought during the tenure of this project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK053392-02
Application #
2856831
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Akolkar, Beena
Project Start
1998-03-15
Project End
1999-12-31
Budget Start
1999-02-15
Budget End
1999-12-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Genetics
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Pape, Utz J; Rahmann, Sven; Sun, Fengzhu et al. (2008) Compound poisson approximation of the number of occurrences of a position frequency matrix (PFM) on both strands. J Comput Biol 15:547-64
Zhang, Kui; Qin, Zhaohui S; Liu, Jun S et al. (2004) Haplotype block partitioning and tag SNP selection using genotype data and their applications to association studies. Genome Res 14:908-16
Sun, Fengzhu; Cui, Jing; Gavras, Haralambos et al. (2003) A novel class of tests for the detection of mitochondrial DNA-mutation involvement in diseases. Am J Hum Genet 72:1515-26
Deng, Minghua; Sun, Fengzhu; Chen, Ting (2003) Assessment of the reliability of protein-protein interactions and protein function prediction. Pac Symp Biocomput :140-51
Zhang, Kui; Sun, Fengzhu; Waterman, Michael S et al. (2003) Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data. Am J Hum Genet 73:63-73
Lai, Yinglei; Sun, Fengzhu (2003) The relationship between microsatellite slippage mutation rate and the number of repeat units. Mol Biol Evol 20:2123-31
Zhang, Kui; Calabrese, Peter; Nordborg, Magnus et al. (2002) Haplotype block structure and its applications to association studies: power and study designs. Am J Hum Genet 71:1386-94
Zhang, Kui; Deng, Minghua; Chen, Ting et al. (2002) A dynamic programming algorithm for haplotype block partitioning. Proc Natl Acad Sci U S A 99:7335-9
Deng, Minghua; Mehta, Shipra; Sun, Fengzhu et al. (2002) Inferring domain-domain interactions from protein-protein interactions. Genome Res 12:1540-8
Li, J; Wang, D; Dong, J et al. (2001) The power of transmission disequilibrium tests for quantitative traits. Genet Epidemiol 21 Suppl 1:S632-7

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