The Paisley Caves in Oregon record the oldest directly dated human remains (DNA) in the Western Hemisphere. More than 100 high-precision radiocarbon dates show that deposits containing artifacts and coprolites ranging in age from 12,450 to 2295 (14)C years ago are well stratified. Western Stemmed projectile points were recovered in deposits dated to 11,070 to 11,340 (14)C years ago, a time contemporaneous with or preceding the Clovis technology. There is no evidence of diagnostic Clovis technology at the site. These two distinct technologies were parallel developments, not the product of a unilinear technological evolution. "Blind testing" analysis of coprolites by an independent laboratory confirms the presence of human DNA in specimens of pre-Clovis age. The colonization of the Americas involved multiple technologically divergent, and possibly genetically divergent, founding groups.

Aims/hypothesis We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. Methods We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. Results In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p<10−5) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p<5×10−8) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. Conclusions/interpretation We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

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Previous research indicates that circulating vitamin D levels are low in many otherwise healthy adults and that there is considerable seasonal variation in 25-hydroxyvitamin D [25(OH)D] concentrations at high latitudes. We examined seasonal variation in 25(OH)D levels in a sample of young adults of diverse ancestry living in the Greater Toronto Area. Three hundred and fifty-one (351) healthy young adults completed both a fall and winter visit during this study. The study was conducted over 2 y (y 1: fall 2007 to winter 2008 and y 2: fall 2008 to winter 2009). At both visits, each participant's serum 25(OH)D concentration was measured. Information was also obtained on skin pigmentation (measured via reflectometer), vitamin D intake, and extent of sun exposure. Overall, the serum 25(OH)D concentration was 54.4 ± 1.3 nmol/L in the fall and 38.4 ± 1.1 nmol/L in the winter. Concentrations differed among ancestral groups at both visits (P < 0.001), with South Asians and East Asians having substantially lower concentrations than Europeans. Skin pigmentation (r(2) = 0.14; P < 0.001), supplemental vitamin D intake (r(2) = 0.09; P < 0.001), sun exposure (r(2) = 0.04; P < 0.001), and study year (r(2) = 0.02; P = 0.017) were predictors of fall 25(OH)D concentrations. During the wintertime, serum 25(OH)D concentrations were associated with concentrations taken in the fall (r(2) = 0.45; P < 0.001), supplemental (r(2) = 0.15; P < 0.001) and dietary vitamin D intake (r(2) = 0.06; P < 0.001), and with study year (r(2) = 0.02; P = 0.009). Our study confirms that serum 25(OH)D concentrations undergo strong seasonal variation at high latitudes and are influenced by vitamin D intake, skin pigmentation, and sun exposure.

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The challenges associated with the retrieval and authentication of ancient DNA (aDNA) evidence are principally due to post-mortem damage which makes ancient samples particularly prone to contamination from “modern” DNA sources. The necessity for authentication of results has led many aDNA researchers to adopt methods considered to be “gold standards” in the field, including cloning aDNA amplicons as opposed to directly sequencing them. However, no standardized protocol has emerged regarding the necessary number of clones to sequence, how a consensus sequence is most appropriately derived, or how results should be reported in the literature. In addition, there has been no systematic demonstration of the degree to which direct sequences are affected by damage or whether direct sequencing would provide disparate results from a consensus of clones.To address this issue, a comparative study was designed to examine both cloned and direct sequences amplified from ∼3,500 year-old ancient northern fur seal DNA extracts. Majority rules and the Consensus Confidence Program were used to generate consensus sequences for each individual from the cloned sequences, which exhibited damage at 31 of 139 base pairs across all clones. In no instance did the consensus of clones differ from the direct sequence. This study demonstrates that, when appropriate, cloning need not be the default method, but instead, should be used as a measure of authentication on a case-by-case basis, especially when this practice adds time and cost to studies where it may be superfluous.

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