Recombination rates in admixed individuals identified by ancestry-based inference

Studies of recombination and how it varies depend crucially on accurate recombination maps. We propose a new approach for constructing high-resolution maps of relative recombination rates based on the observation of ancestry switch points among admixed individuals. We show the utility of this approach using simulations and by applying it to SNP genotype data from a sample of 2,565 African Americans and 299 African Caribbeans and detecting several hundred thousand recombination events. Comparison of the inferred map with high-resolution maps from non-admixed populations provides evidence of fine-scale differentiation in recombination rates between populations. Overall, the admixed map is well predicted by the average proportion of admixture and the recombination rate estimates from the source populations. The exceptions to this are in areas surrounding known large chromosomal structural variants, specifically inversions. These results suggest that outside of structurally variable regions, admixture does not substantially disrupt the factors controlling recombination rates in humans.     

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ～5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.     

Physiogenomic resources for rat models of heart, lung and blood disorders

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.     

Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

A copy number variation morbidity map of developmental delay

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ～14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.     

Asian summer monsoon precipitation recorded by stalagmite oxygen isotopic composition in the western Loess Plateau during AD1875―2003 and its linkage with ocean-atmosphere system

Based on 5 high-precision ^230Th dates and 103 stable oxygen isotope ratios （51eO） obtained from the top 16 mm of a stalagmite collected from Wanxiang Cave, Wudu, Gansu, variation of monsoonal precipitation in the modern Asian Monsoon （AM） marginal zone over the past 100 years was reconstructed. Comparison of the speleothem δ^18O record with instrumental precipitation data at Wudu in the past 50 years indicates a high parallelism between the two curves, suggesting that the speleothem δ^18O is a good proxy for the AM strength and associated precipitation, controlled by ＂amount effect＂ of the precipitation. Variation of the monsoonal precipitation during the past 100 years can be divided into three stages, increasing from AD 1875 to 1900, then decreasing from AD 1901 to 1946, and increasing again thereafter. This variation is quite similar to that of the Drought/Flooding index archived from Chinese historical documents. This speleothem-derived AM record shows a close association with the Pacific Decadal Oscillation （PDO） between AD 1875 and 1977, with higher monsoonal precipitation corresponding to cold PDO phase and vice versa at decadal timescale. The monsoonal precipitation variation is out of phase with the PDO after AD 1977, probably resulting from the decadal climate jump in the north Pacific occurring at around AD 1976/77. These results demonstrate a strong linkage between the AM and associated precipitation and the Pacific Ocean via ocean/atmosphere interaction. This relationship will aid to forecast future hydrological cycle for the AM monsoon region, and to improve forecasting potential of climatic model with observation data from cave.     

Mass mortality of salamanders ( Ambystoma tigrinum ) by bacteria ( Acinetobacter ) in an oligotrophic seepage mountain lake

Of the 13 lakes in the central Wasatch Mountains with tiger salamander ( Ambystoma tigrinum ) populations, salamander mass mortalities occurred in four seepage lakes that experienced extensive lowering of the water levels during the summer. The largest of these lakes, the oligotrophic Desolation Lake, was studied to determine the cause of the mortality phenomenon. The recurrent annual mass mortality involved both breeding adults and young-of-the-year. Rate kinetics suggest that mortality rate doubles with a fivefold increase in the number of aquatic young salamanders. The proximate cause of the mass mortality was identified as a bacterium, Acinetobacter sp. Desolation Lake and a seepage lake that did not experience the mass mortality were studied for the presence of Acinetobacter . Both lakes experienced two bacteria cycles: the first in early summer involved gram-positive bacteria, and the second in late summer involved gram-negative bacteria (mostly coliform bacteria and Acinetobacter ). The mass mortalities were associated with the late-summer gram-negative bacterial bloom, and Acinetobacter was found in large numbers in Desolation Lake. Algae, as well as other photosynthetic plants, were not present in large numbers. Since these lakes are growth-limited with respect to nitrogen and not with respect to phosphate, and since Desolation Lake had extensive lowering of the lake level during the summer, the biological cycle of the lake is proposed to be due to atmospheric and sheep-produced nitrogen products within the watershed. In this unstable lake system, bacteria are primarily responsible for incorporation of nitrogen in the food chain. The timing of the cyclical events depends on total winter precipitation.     

First dairying in green Saharan Africa in the fifth millennium BC

In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities. The remarkable rock art found widely across the region depicts cattle herding among early Saharan pastoral groups, and includes rare scenes of milking; however, these images can rarely be reliably dated. Although the faunal evidence provides further confirmation of the importance of cattle and other domesticates, the scarcity of cattle bones makes it impossible to ascertain herd structures via kill-off patterns, thereby precluding interpretations of whether dairying was practiced. Because pottery production begins early in northern Africa the potential exists to investigate diet and subsistence practices using molecular and isotopic analyses of absorbed food residues. This approach has been successful in determining the chronology of dairying beginning in the 'Fertile Crescent' of the Near East and its spread across Europe. Here we report the first unequivocal chemical evidence, based on the δ(13)C and Δ(13)C values of the major alkanoic acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium bc. Interpretations are supported by a new database of modern ruminant animal fats collected from Africa. These findings confirm the importance of 'lifetime products', such as milk, in early Saharan pastoralism, and provide an evolutionary context for the emergence of lactase persistence in Africa.     

Life choices simulation: Model and methodology

The life choices stimulation (LCS) is a computer-managed simulation which permits participants to explore the impact of decision making in an extended time frame. It is designed primarily for individuals who wish to explore a variety of possible futures and to develop an appreciation for the complexity of relationships and career planning. A general systems approach was used to design a model of complexity within the simulation. “Situation” scenarios were developed to represent common life experiences to which the participant must respond (such as single parenting, divorce, career choice, and old age). The realism of the simulation is provided by a supporting data base which includes such data points as average income of male and female workers, types of employment and their salary levels, and time unit allowances for life-style choices. These data are kept current and are used to generate the results of various choices. This paper describes the process of simulation development, outlines the LCS, and suggests research uses.