The Genographic Project Public Participation Mitochondrial DNA Database

Abstract

The Genographic Project is studying the genetic signatures of ancient human migrations and creating an open-source research database. It allows members of the public to participate in a real-time anthropological genetics study by submitting personal samples for analysis and donating the genetic results to the database. We report our experience from the first 18 months of public participation in the Genographic Project, during which we have created the largest standardized human mitochondrial DNA (mtDNA) database ever collected, comprising 78,590 genotypes. Here, we detail our genotyping and quality assurance protocols including direct sequencing of the mtDNA HVS-I, genotyping of 22 coding-region SNPs, and a series of computational quality checks based on phylogenetic principles. This database is very informative with respect to mtDNA phylogeny and mutational dynamics, and its size allows us to develop a nearest neighbor–based methodology for mtDNA haplogroup prediction based on HVS-I motifs that is superior to classic rule-based approaches. We make available to the scientific community and general public two new resources: a periodically updated database comprising all data donated by participants, and the nearest neighbor haplogroup prediction tool.

Sephardic signature in haplogroup T mitochondrial DNA

“…This is a common mutation that has independently arisen in many backgrounds. 13 The phylogeny of T2e was found to be star-like with the most frequent haplotype the ancestral sequence (16126T-16153A-16294T, not considering positions 16296, 16519, or control region 2), with numerous much smaller clusters descended from that central node. In a previous study of haplogroup T control region, 39 T2e ('T5') was not star-like, presumably because there were only 15 T2e samples at the time.…”

“…Studies for comparison populations were selected on the basis of large size and availability. If frequencies of subhaplogroups were provided in the text 13,24,25 or in online supplementary material, 26,27 those assignments were used with the assumption that T3¼T2c, T5¼T2e, and T*¼T other. Otherwise, control region 1 sequences were inspected in the text 24,28 or supplementary materials 4,5,26,29,30 and assigned to subhaplogroups of T. Assignment criteria used were 16163G-16189C (T1), 16304C (T2b), 16292T (T2c), 16153A (T2e), 16324C (T4) within the context of also having 16126C, 16294T (T); remaining motifs were assigned as 'T other' .…”

“…The large data sets from mitosearch and Genographic are in close accordance with the incidence of Haplogroup T in the smaller British and Irish Isles study (Scotland, Wales, England, Cornwall, Ireland) of B9% and likely reflect the large number of Americans with Western European ancestry that comprise these data sets. 13 Haplogroup T, Sephardic population. The four studies involving Sephardic populations have incidences of T of 4.9%, not reported, 14 and 11.1%.…”

“…2,3 Behar et al 4,5 have investigated the size of the founder effect in 15 Jewish communities with samples of mitochondrial DNA obtained from 1725 individuals. Their impressive undertaking has provided, as they note, 'y a nearly comprehensive picture of the maternal genetic landscape of the entire Jewish population' (p. 13).…”

“…The motif falls within haplogroup T, [10][11][12] which is present in close to 10% of individuals with European ancestry. 3,13 Criteria for inclusion in T in the first control region are transitions from base 'C' to base 'T' at positions 16126 and 16294. The suspected Sephardic haplotype is further identifiable as a branch of T2e, 14 formerly T5, 2 characterized by the addition of a mutation at 16153 in the first control region 2 (and at 150 in the second control region).…”