Mitochondrial genomic variation associated with higher mitochondrial copy number: the Cache County Study on Memory Health and Aging
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- 作者：Perry G Ridge (11) (12)
Taylor J Maxwell (13)
Spencer J Foutz (11)
Matthew H Bailey (11)
Christopher D Corcoran (14) (15)
JoAnn T Tschanz (15) (16)
Maria C Norton (15) (16) (17)
Ronald G Munger (15) (18)
Elizabeth O’Brien (19)
Richard A Kerber (19)
Richard M Cawthon (20)
John SK Kauwe (11) - 刊名：BMC Bioinformatics
- 出版年：2014
- 出版时间：May 2014
- 年：2014
- 卷：15
- 期：7-supp
- 全文大小：
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Taylor J Maxwell (13)
Spencer J Foutz (11)
Matthew H Bailey (11)
Christopher D Corcoran (14) (15)
JoAnn T Tschanz (15) (16)
Maria C Norton (15) (16) (17)
Ronald G Munger (15) (18)
Elizabeth O’Brien (19)
Richard A Kerber (19)
Richard M Cawthon (20)
John SK Kauwe (11)
11. Department of Biology, Brigham Young University, Provo, UT, USA
12. ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
13. Human Genetics Center, University of Texas School of Public Health, Houston, TX, USA
14. Department of Mathematics and Statistics, Utah State University, Logan, UT, USA
15. Center for Epidemiologic Studies, Utah State University, Logan, UT, USA
16. Department of Psychology, Utah State University, Logan, UT, USA
17. Department of Family Consumer and Human Development, Utah State University, Logan, UT, USA
18. Department of Nutrition, Dietetics, and Food Sciences, Utah State University, Logan, UT, USA
19. Department of Epidemiology and Population Health, University of Louisville, Louisville, KY, USA
20. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA - ISSN：1471-2105
文摘
Background The mitochondria are essential organelles and are the location of cellular respiration, which is responsible for the majority of ATP production. Each cell contains multiple mitochondria, and each mitochondrion contains multiple copies of its own circular genome. The ratio of mitochondrial genomes to nuclear genomes is referred to as mitochondrial copy number. Decreases in mitochondrial copy number are known to occur in many tissues as people age, and in certain diseases. The regulation of mitochondrial copy number by nuclear genes has been studied extensively. While mitochondrial variation has been associated with longevity and some of the diseases known to have reduced mitochondrial copy number, the role that the mitochondrial genome itself has in regulating mitochondrial copy number remains poorly understood. Results We analyzed the complete mitochondrial genomes from 1007 individuals randomly selected from the Cache County Study on Memory Health and Aging utilizing the inferred evolutionary history of the mitochondrial haplotypes present in our dataset to identify sequence variation and mitochondrial haplotypes associated with changes in mitochondrial copy number. Three variants belonging to mitochondrial haplogroups U5A1 and T2 were significantly associated with higher mitochondrial copy number in our dataset. Conclusions We identified three variants associated with higher mitochondrial copy number and suggest several hypotheses for how these variants influence mitochondrial copy number by interacting with known regulators of mitochondrial copy number. Our results are the first to report sequence variation in the mitochondrial genome that causes changes in mitochondrial copy number. The identification of these variants that increase mtDNA copy number has important implications in understanding the pathological processes that underlie these phenotypes.