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

Abstract

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.

Hi-MC: A novel method for high-throughput mitochondrial haplogroup classification

“…In this newer reference dataset, the most common reJorted haJlogrouJ is A (25%) followed by B (15%) and C (9%) 38 comJared with a higher A (A2) frequency in the Jresent study (39% ; Table 2). Overall, the distribution of Native American and EuroJean haJlogrouJs in the MXL samJles from HaJMaJ Phase III is similar to the distribution observed in the NHANES Mexican American samJles 22 . No African lineage mitochondrial haJlogrouJs were identified among the HaJMaJ MXL samJles.…”

“…The SNPs were selected for broad classification of EuroJean, African, and Native American mitochondrial haJlogrouJ lineages as Jreviously described 22 . Briefly, SNPs were chosen using Phylotree 21 and an extensive literature search for Jrior studies related to mitochondrial haJlogrouJ classification 24-2g .…”

The Potential Application of Mitochondrial Medicine in Toxicologic Poisoning

“…Cybrids from different mitochondrial haplogroups were generated using platelets of different haplogroups fused with the osteosarcoma ρ0 cell line. Cybrids with haplogroups Uk and J were found to have lower ATP production, lower oxygen consumption, and decreased mtDNA when compared to haplogroup H [18,19].…”

“…Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Other important clinical findings include hemiparesis, seizures, visual loss, and progressive dementia [19]. At this time, MELAS largely remains an untreatable disease where deaths typically occur by the fourth decade of life from the above complications.…”

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“…Sixty-three SNPs were selected, the majority of which are located in the coding region of the mitochondrial genome. Three Sequenom genotyJing assay Jools including all of these SNPs were designed using the MassARRAY software 22 . As described in Mitchell et al 22 , the custom SNP Janel was genotyJed in the National Health and Nutrition Examination Surveys (NHANES) accessed by the EJidemiologic Architecture for Genes Linked to Environment (EAGLE) 28 , a study site of the PoJulation Architecture using Genomics and EJidemiology (PAGE) I study 29 .…”