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.

Figure 1. Mitochondrial haplogroup classification tree

Simplified mitochondrial phylogenetic tree for classification of European (blue), African (red), and Native American/Asian (green) mitochondrial haplogroup lineages; Eurasian macrohaplogroups are in orange and the checkered boxes indicate haplogroups that were included in counts of the corresponding parent Eurasian macrohaplogroup. mtSNPs in bold are found in a single haplogroup and those followed by (!) indicate reversions.

Figure 2. Distribution of mitochondrial haplogroup lineages by survey

Data include 19,608 samples genotyped from NHANES III, NHANES 1999–2002, and NHANES 2007–2008.

Figure 3. Distribution of mitochondrial haplogroup lineages by self-identified race/ethnicity

Data include only the total classified within each self-identified race/ethnicity. Abbreviations: Cont. NH (Continuous NHANES; includes1999–2002 and 2007–2008 data sets), NHIII (NHANES III), NHW (non-Hispanic white), NHB (non-Hispanic black), MA (Mexican American)