Sequences From First Settlers Reveal Rapid Evolution in Icelandic mtDNA Pool

A major task in human genetics is to understand the nature of the evolutionary processes that have shaped the gene pools of contemporary populations. Ancient DNA studies have great potential to shed light on the evolution of populations because they provide the opportunity to sample from the same population at different points in time. Here, we show that a sample of mitochondrial DNA (mtDNA) control region sequences from 68 early medieval Icelandic skeletal remains is more closely related to sequences from contemporary inhabitants of Scotland, Ireland, and Scandinavia than to those from the modern Icelandic population. Due to a faster rate of genetic drift in the Icelandic mtDNA pool during the last 1,100 years, the sequences carried by the first settlers were better preserved in their ancestral gene pools than among their descendants in Iceland. These results demonstrate the inferential power gained in ancient DNA studies through the application of population genetics analyses to relatively large samples

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Lithic materials in high fluvial terraces of the central Pyrenean piedmont (Ebro Basin, Spain)

Lithic materials from Lower Palaeolithic are scarce in the Ebro Basin. Archaeological surveys carried out in some alluvial terraces on central Pyrenean piedmont have unearthed three new sites with remains of lithic industries related to cobble and core technology and large cutting tools. In the upper terrace levels (T1 and T2) from the Alcanadre and Cinca rivers, some pieces have been recovered on the surfaces: cobble-tools at Las Fitas and bifacial tools at San Quílez. The approximate age of these levels ranges between 780 ka and 1000 ka, established by paleomagnetism and evolutionary stages of calcrete. A cleaver was interbedded into a terrace (T5 level) of a minor tributary of the Cinca River (Olriols), whose age has been established at a regional scale between 178/151 ka. This T5 level is related to one of the cold phases of greater advance of Pyrenean glaciers during MIS 6.These new findings help us to widen our knowledge of a poorly known period of the human occupation of the middle Iberian basin. The chronological imprecision of most of the lithic materials has been partially overcome by means of geomorphological data, which offers a generic chrono-cultural framework for the people who used them.Fil: Montes, Lourdes. Universidad de Zaragoza; EspañaFil: Domingo, Rafael. Universidad de Zaragoza; EspañaFil: Peña Monné, José Luis. Universidad de Zaragoza; EspañaFil: Sampietro Vattuone, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Laboratorio de Geoarqueología; ArgentinaFil: Rodríguez Ochoa, Rafael. Universidad de Lleida; EspañaFil: Utrilla, Pilar. Universidad de Zaragoza; Españ

Geomorphological, chronological, and paleoenvironmental context of the Mousterian site at Roca San Miguel (Arén, Huesca, Spain) from the penultimate to the last glacial cycle

The Roca San Miguel (RSM) archaeological site was occupied during Mousterian times. Here we present a geoarchaeological and paleoenvironmental reconstruction of the site. Five stratigraphic units (A to E) formed by different archaeological levels are identified. Three optically stimulated luminescence (OSL) ages show that Unit A dates to between 169.6 ± 9.1 and 151.9 ± 11.1 ka, during the penultimate glacial period (PGP), and contains numerous signs of recurring hearths. Unit B is unexcavated. Unit C dates to between 118.9 ± 11.5 and 103.4 ± 6.9 ka (late Eemian-marine isotope stage (MIS) 5d) and shows an abundance of lithic remains as well as some faunal elements. Unit C is covered by Unit D, which incorporates materials moved downslope, and is dated at 81.2 ± 4.7 ka. These OSL ages concur with U/Th ages (129.3 ± 1.5 and 123.6 ± 0.6 ka) derived from a flowstone covered by both -C and D- post-flowstone units. Finally, Unit E covers the archaeological site, which was partially eroded during MIS2. The robust and well-constrained chronology of the RSM site and surroundings enables the establishment of its evolutionary model from the PGP to the last glacial cycle. The RSM site is the oldest Neanderthal occupation accurately dated in the Pre-Pyrenean region.Fil: Peña Monné, Jose Luis. Universidad de Zaragoza. Facultad de Filosofía y Letras; EspañaFil: Montes, Lourdes. Universidad de Zaragoza. Facultad de Filosofía y Letras; EspañaFil: Sampietro Vattuone, Maria Marta. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Laboratorio de Geoarqueología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Domingo, Rafael. Universidad de Zaragoza. Facultad de Filosofía y Letras; EspañaFil: Medialdea, Alicia. Cenieh; EspañaFil: Bartolome, Miguel Alberto. Museo Nacional de Ciencias Naturales; EspañaFil: Rubio Fernández, Virginia. Universidad Autónoma de Madrid; EspañaFil: García Giménez, Rosario. Universidad Autónoma de Madrid; EspañaFil: Turú, Valentin. Fundació Marcel Chevallier; AndorraFil: Ros, Xavier. Fundació Marcel Chevallier; AndorraFil: Baró, Pere. Fundació Marcel Chevallier; AndorraFil: Bernal Wormull, Luis. Consejo Superior de Investigaciones Científicas; EspañaFil: Edwards, R. Lawrence. University of Minnesota; Estados Unido

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis