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Characterization of mitochondrial haplogroups in a large population-based sample from the United States


Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Using these mtDNA markers, we constructed a mitochondrial haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing mitochondrial haplogroups in a population-based sample from the United States, and the first study characterizing mitochondrial haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The mitochondrial haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8 %), but was considerably lower in admixed populations including non-Hispanic blacks (88.3 %), Mexican Americans (81.8 %), and other Hispanics (61.6 %), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The mitochondrial haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease.

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Genotyping in NHANES was supported in part by the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study (U01HG004798 and its ARRA supplements) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study established by the National Human Genome Research Institute (NHGRI). We at EAGLE would like to thank Melissa Allen and Paxton Baker for their work in genotyping the samples through the Center for Human Genetic Research Open Wet Lab (OWL) and DNA Resources Core, respectively. We would also like to thank Dr. Geraldine McQuillan and Jody McLean for their help in accessing the Genetic NHANES data. The Vanderbilt University Center for Human Genetics Research, Computational Genomics Core provided computational and/or analytical support for this work. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institutes for Health or the Centers for Disease Control and Prevention.

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Correspondence to Dana C. Crawford.

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Mitchell, S.L., Goodloe, R., Brown-Gentry, K. et al. Characterization of mitochondrial haplogroups in a large population-based sample from the United States. Hum Genet 133, 861–868 (2014).

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  • Much Recent Common Ancestor
  • Mitochondrial Haplogroup
  • Mitochondrial Genetic Variation
  • Molecular Anthropology
  • Mitochondrial SNPs