The distinctive geographic patterns of common pigmentation variants at the OCA2 gene.

Oculocutaneous Albinism type 2 (OCA2) is a gene of great interest because of genetic variation affecting normal pigmentation variation in humans. The diverse geographic patterns for variant frequencies at OCA2 have been evident but have not been systematically investigated, especially outside of Europe. Here we examine population genetic variation in and near the OCA2 gene from a worldwide perspective. The very different patterns of genetic variation found across world regions suggest strong selection effects may have been at work over time. For example, analyses involving the variants that affect pigmentation of the iris argue that the derived allele of the rs1800407 single nucleotide polymorphism, which produces a hypomorphic protein, may have contributed to the previously demonstrated positive selection in Europe for the enhancer variant responsible for light eye color. More study is needed on the relationships of the genetic variation at OCA2 to variation in pigmentation in areas beyond Europe.

Evaluating 130 microhaplotypes across a global set of 83 populations.

Today the primary DNA markers used in forensics are short tandem repeat (STR) polymorphisms (STRPs), initially selected because they are highly polymorphic. However, the increasingly common need to deal with samples with a mixture of DNA from two or more individuals sometimes is complicated by the inherent stutter involved with PCR amplification, especially in strongly unbalanced mixtures when the minor component coincides with the stutter range of the major component. Also, the STRPs in use provide little evidence of ancestry of a single source sample beyond broad "continental" resolution. Methodologies for analyzing DNA have become much more powerful in recent years. Massively parallel sequencing (MPS) is a new method being considered for routine use in forensics. Primarily to aid in mixture deconvolution and avoid the issue of stutter, we have begun to investigate a new type of forensic marker, microhaplotype loci, that will provide useful information on mixtures of DNA and on ancestry when typed using massively parallel sequencing (MPS). We have identified 130 loci and estimated their haplotype (allele) frequencies in 83 different population samples. Many of these loci are shown to be highly informative for individual identification and for mixture identification and deconvolution.

Genetic variation in Tunisia in the context of human diversity worldwide.

OBJECTIVES: North Africa has a complex demographic history of migrations from within Africa, Europe, and the Middle East. However, population genetic studies, especially for autosomal genetic markers, are few relative to other world regions. We examined autosomal markers for eight Tunisian and Libyan populations in order to place them in a global context. MATERIALS AND METHODS: Data were collected by TaqMan on 399 autosomal single nucleotide polymorphisms on 331 individuals from Tunisia and Libya. These data were combined with data on the same SNPs previously typed on 2585 individuals from 57 populations from around the world. Where meaningful, close by SNPs were combined into multiallelic haplotypes. Data were evaluated by clustering, principal components, and population tree analyses. For a subset of 102 SNPs, data from the literature on seven additional North African populations were included in analyses. RESULTS: Average heterozygosity of the North African populations is high relative to our global samples, consistent with a complex demographic history. The Tunisian and Libyan samples form a discrete cluster in the global and regional views and can be separated from sub-Sahara, Middle East, and Europe. Within Tunisia the Nebeur and Smar are outlier groups. Across North Africa, pervasive East-West geographical patterns were not found. DISCUSSION: Known historical migrations and invasions did not displace or homogenize the genetic variation in the region but rather enriched it. Even a small region like Tunisia contains considerable genetic diversity. Future studies across North Africa have the potential to increase our understanding of the historical demographic factors influencing the region. Am J Phys Anthropol 161:62-71, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

52 additional reference population samples for the 55 AISNP panel.

Ancestry inference for a person using a panel of SNPs depends on the variation of frequencies of those SNPs around the world and the amount of reference data available for calculation/comparison. The Kidd Lab panel of 55 AISNPs has been incorporated in commercial kits by both Life Technologies and Illumina for massively parallel sequencing. Therefore, a larger set of reference populations will be useful for researchers using those kits. We have added reference population allele frequencies for 52 population samples to the 73 previously entered so that there are now allele frequencies publicly available in ALFRED and FROG-kb for a total of 125 population samples.

Current sequencing technology makes microhaplotypes a powerful new type of genetic marker for forensics.

SNPs that are molecularly very close (<10kb) will generally have extremely low recombination rates, much less than 10(-4). Multiple haplotypes will often exist because of the history of the origins of the variants at the different sites, rare recombinants, and the vagaries of random genetic drift and/or selection. Such multiallelic haplotype loci are potentially important in forensic work for individual identification, for defining ancestry, and for identifying familial relationships. The new DNA sequencing capabilities currently available make possible continuous runs of a few hundred base pairs so that we can now determine the allelic combination of multiple SNPs on each chromosome of an individual, i.e., the phase, for multiple SNPs within a small segment of DNA. Therefore, we have begun to identify regions, encompassing two to four SNPs with an extent of <200bp that define multiallelic haplotype loci. We have identified candidate regions and have collected pilot data on many candidate microhaplotype loci. Here we present 31 microhaplotype loci that have at least three alleles, have high heterozygosity, are globally informative, and are statistically independent at the population level. This study of microhaplotype loci (microhaps) provides proof of principle that such markers exist and validates their usefulness for ancestry inference, lineage-clan-family inference, and individual identification. The true value of microhaplotypes will come with sequencing methods that can establish alleles unambiguously, including disentangling of mixtures, because a single sequencing run on a single strand of DNA will encompass all of the SNPs.

Haplotype structure and positive selection at TLR1.

Toll-like receptor 1, when dimerized with Toll-like receptor 2, is a cell surface receptor that, upon recognition of bacterial lipoproteins, activates the innate immune system. Variants in TLR1 associate with the risk of a variety of medical conditions and diseases, including sepsis, leprosy, tuberculosis, and others. The foremost of these is rs5743618 c.2079T>G(p.(Ile602Ser)), the derived allele of which is associated with reduced risk of sepsis, leprosy, and other diseases. Interestingly, 602Ser, which shows signatures of selection, inhibits TLR1 surface trafficking and subsequent activation of NFκB upon recognition of a ligand. This suggests that reduced TLR1 activity may be beneficial for human health. To better understand TLR1 variation and its link to human health, we have typed all 7 high-frequency missense variants (>5% in at least one population) along with 17 other variants in and around TLR1 in 2548 individuals from 56 populations from around the globe. We have also found additional signatures of selection on missense variants not associated with rs5743618, suggesting that there may be multiple functional alleles under positive selection in this gene.