The GenoChip: A New Tool for Genetic Anthropology

Abstract

The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics.

Geographic population structure analysis of worldwide human populations infers their biogeographical origins

“…Yet, estimated by the percentage of individuals correctly assigned to their country of origin, the accuracy of PCA and SPA are relatively low for Europeans (40±5% and 45±5%, respectively) and much lower for non-Europeans 12 . Such results suggest limitations with these approaches for biogeographical inference 12,15,16 , coupled with a possible limitation of commonly used genotyping arrays in capturing fine sub-structure 17,18 . As patterns of genetic diversity in human populations or admixture are frequently described as genome-based estimates of several ancestries that sums to 100% 19-21 , we speculated that an admixture-based approach may yield better results.…”

Reconstructing Druze population history

“…Between the years 2005 and 2012, participants were tested for either their mtDNA or Y chromosomal haplogroups. Participants tested after 2012 were genotyped on the GenoChip microarray that includes nearly 150,000 non-functional61 highly informative Y-chromosomal, mitochondrial, autosomal and X-chromosomal markers62. We accessed the Genographic Project’s database through http://geno-web.nationalgeographic.com/geno2/dist/.…”

“…For consistency, we analysed ~94,000 autosomal SNPs that overlapped with the Genochip microarray and allowed a high GPS accuracy to be achieved62. PLINK (1.07) was used to test the relatedness among Druze using the –genome flag64.…”

Genographic Project

“…More specifically, Genographic scientists and other investigators are analyzing autosomal SNP variation in human DNA samples (many collected during Phase I, some previously obtained in unrelated studies) with the novel GenoChip microarray, which is specifically designed for anthropological genetics research (Elhaik et al, 2013). This SNP array is an Illumina HD iSelect genotyping bead array with over 130 000 highly informative autosomal and X-chromosomal SNPs ascertained from over 450 worldwide populations analyzed in the 1000 Genomes Project (2010) and the HapMap Project Durban et al, 2010) and other published studies (Rasmussen et al, 2010(Rasmussen et al, , 2011.…”

“…The chip was validated by genotyping over 1000 samples from the 1000 Genomes Project, Family Tree DNA, and Genographic Projects (Elhaik et al, 2013), and served as a worldwide reference database for the project. Initial results indicate a 99.5% concordance between the GenoChip and the 1000 Genomes Project data sets, as well as SNP density of approximately (1/100 000) bases over 92% of the human genome.…”