The Diversity of REcent and Ancient huMan (DREAM): A New Microarray for Genetic Anthropology and Genealogy, Forensics, and Personalized Medicine

Abstract

The human population displays wide variety in demographic history, ancestry, content of DNA derived from hominins or ancient populations, adaptation, traits, copy number variation, drug response, and more. These polymorphisms are of broad interest to population geneticists, forensics investigators, and medical professionals. Historically, much of that knowledge was gained from population survey projects. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism genotyping, their design specifications are limited and they do not allow a full exploration of biodiversity. We thereby aimed to design the Diversity of REcent and Ancient huMan (DREAM)—an all-inclusive microarray that would allow both identification of known associations and exploration of standing questions in genetic anthropology, forensics, and personalized medicine. DREAM includes probes to interrogate ancestry informative markers obtained from over 450 human populations, over 200 ancient genomes, and 10 archaic hominins. DREAM can identify 94% and 61% of all known Y and mitochondrial haplogroups, respectively, and was vetted to avoid interrogation of clinically relevant markers. To demonstrate its capabilities, we compared its FST distributions with those of the 1000 Genomes Project and commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, DREAM’s autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. DREAM performances are further illustrated in biogeographical, identical by descent, and copy number variation analyses. In summary, with approximately 800,000 markers spanning nearly 2,000 genes, DREAM is a useful tool for genetic anthropology, forensic, and personalized medicine studies.

Node-Based Resilience Measure Clustering with Applications to Noisy and Overlapping Communities in Complex Networks

“…The practical utility of the NBR-Clust clustering method described in this paper is further demonstrated in [16][17][18], where it is applied to new medical and biological datasets. In [16], the method is applied to a database of Autism Spectrum Disorder phenotypes.…”

Ancient ancestry informative markers for identifying fine-scale ancient population structure in Eurasians

“…Ancestry informative markers (AIMs) are some of the most useful tools in addressing population, biomedical, forensics, and evolutionary questions that remain in use today [8,[31][32][33]. However it is unclear to what extent known AIMs are applicable to ancient genomic data, characterized by high missingness and haploidy [1].…”

“…AIMs are SNPs which exhibit large variation in minor allele frequencies (MAF) among populations. Over the past two centuries and to this date, geneticists have scoured genomes for these patterns and produced numerous AIM sets to determine an individual's ancestry, detect stratification in biomedical studies, infer geographic structure, find risk loci in a candidate region, and localize biogeographical origins [e.g., 8,9,[16][17][18]. AIM panels can delineate population structure in a cost effective manner by detecting variation in individual ancestry that can confound methods like Mendelian Randomization trials, association analyses, and forensic investigations in increasing false positive results or reducing power [e.g., 19].…”

“…Although initially preferred due to the high cost of sequencing, which has decreased with time, AIMs are still highly used in forensics, carrier screening, and biogeography in both microarrays [e.g., 8,20] and whole genomic data [21]. Admixture mapping is another powerful method to map phenotypic variation or diseases that show differential risk by ancestry.…”

“…It soon became clear that the allele frequency spectrum obtained through microarrays is more skewed for some populations than for other ones due to the choice of SNP panels [7]. The Human Origins and various Illumina microarrays (including the Illumina Human 660W-Quad, which is very similar to the Illumina 610-Quad array) were shown to distort the population structure for modern day populations compared to larger genomic databases and underreport the biodiversity compared to microarrays customized for population genetics [8,9], which results in an ascertainment bias.…”