A combined long-range phasing and long haplotype imputation method to impute phase for SNP genotypes

<p>Abstract</p> <p>Background</p> <p>Knowing the phase of marker genotype data can be useful in genome-wide association studies, because it makes it possible to use analysis frameworks that account for identity by descent or parent of origin of alleles and it can lead to a large increase in data quantities via genotype or sequence imputation. Long-range phasing and haplotype library imputation constitute a fast and accurate method to impute phase for SNP data.</p> <p>Methods</p> <p>A long-range phasing and haplotype library imputation algorithm was developed. It combines information from surrogate parents and long haplotypes to resolve phase in a manner that is not dependent on the family structure of a dataset or on the presence of pedigree information.</p> <p>Results</p> <p>The algorithm performed well in both simulated and real livestock and human datasets in terms of both phasing accuracy and computation efficiency. The percentage of alleles that could be phased in both simulated and real datasets of varying size generally exceeded 98% while the percentage of alleles incorrectly phased in simulated data was generally less than 0.5%. The accuracy of phasing was affected by dataset size, with lower accuracy for dataset sizes less than 1000, but was not affected by effective population size, family data structure, presence or absence of pedigree information, and SNP density. The method was computationally fast. In comparison to a commonly used statistical method (fastPHASE), the current method made about 8% less phasing mistakes and ran about 26 times faster for a small dataset. For larger datasets, the differences in computational time are expected to be even greater. A computer program implementing these methods has been made available.</p> <p>Conclusions</p> <p>The algorithm and software developed in this study make feasible the routine phasing of high-density SNP chips in large datasets.</p

Incidence and mortality rates of selected infection-related cancers in Puerto Rico and in the United States

<p>Abstract</p> <p>Background</p> <p>In 2002, 17.8% of the global cancer burden was attributable to infections. This study assessed the age-standardized incidence and mortality rates of stomach, liver, and cervical cancer in Puerto Rico (PR) for the period 1992-2003 and compared them to those of Hispanics (USH), non-Hispanic Whites (NHW), and non-Hispanic Blacks (NHB) in the United States (US).</p> <p>Methods</p> <p>Age-standardized rates [ASR(World)] were calculated based on cancer incidence and mortality data from the PR Cancer Central Registry and SEER, using the direct method and the world population as the standard. Annual percent changes (APC) were calculated using the Poisson regression model from 1992-2003.</p> <p>Results</p> <p>The incidence and mortality rates from stomach, liver and cervical cancer were lower in NHW than PR; with the exception of mortality from cervical cancer which was similar in both populations. Meanwhile, the incidence rates of stomach, liver and cervical cancers were similar between NHB and PR; except for NHB women who had a lower incidence rate of liver cancer than women in PR. NHB had a lower mortality from liver cancer than persons in PR, and similar mortality from stomach cancer.</p> <p>Conclusions</p> <p>The burden of liver, stomach, and cervical cancer in PR compares to that of USH and NHB and continues to be a public health priority. Public health efforts are necessary to further decrease the burden of cancers associated to infections in these groups, the largest minority population groups in the US. Future studies need to identify factors that may prevent infections with cancer-related agents in these populations. Strategies to increase the use of preventive strategies, such as vaccination and screening, among minority populations should also be developed.</p

Seroprevalence of 13 common pathogens in a rapidly growing U.S. minority population: Mexican Americans from San Antonio, TX

<p>Abstract</p> <p>Background</p> <p>Infection risks vary among individuals and between populations. Here we present information on the seroprevalence of 13 common infectious agents in a San Antonio-based sample of Mexican Americans. Mexican Americans represent the largest and most rapidly growing minority population in the U.S., and they are also considered a health disparities population.</p> <p>Methods</p> <p>We analyzed 1227 individuals for antibody titer to <it>Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii</it>, cytomegalovirus, Epstein-Barr virus, herpes simplex virus-1, herpes simplex virus-2 (HSV-2), human herpesvirus-6 (HHV-6), varicella zoster virus (VZV), adenovirus-36, hepatitis A virus, and influenza A and B. Seroprevalence was examined as a function of sex, age, household income, and education.</p> <p>Results</p> <p>Seroprevalence estimates ranged from 9% for <it>T. gondii</it> to 92% for VZV, and were similar in both sexes except for HSV-2, which was more prevalent in women. Many pathogens exhibited a significant seroprevalence change over the examined age range (15-94 years), with 7 pathogens increasing and HHV-6 decreasing with age. Socioeconomic status significantly correlated with serostatus for some pathogens.</p> <p>Conclusions</p> <p>Our findings demonstrate substantial seroprevalence rates of these common infections in this sample of Mexican Americans from San Antonio, Texas that suffers from high rates of chronic diseases including obesity and type-2 diabetes.</p

Farming, foreign holidays, and vitamin D in Orkney

Orkney, north of mainland Scotland, has the world's highest prevalence of multiple sclerosis (MS); vitamin D deficiency, a marker of low UV exposure, is also common in Scotland. Strong associations have been identified between vitamin D deficiency and MS, and between UV exposure and MS independent of vitamin D, although causal relationships remain to be confirmed. We aimed to compare plasma 25-hydroxyvitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. We compared mean vitamin D and prevalence of deficiency in cross-sectional study data from participants in the Orkney Complex Disease Study (ORCADES) and controls in the Scottish Colorectal Cancer Study (SOCCS). We used multivariable regression to identify factors associated with vitamin D levels in Orkney. Mean (standard deviation) vitamin D was significantly higher among ORCADES than SOCCS participants (35.3 (18.0) and 31.7 (21.2), respectively). Prevalence of severe vitamin D deficiency was lower in ORCADES than SOCCS participants (6.6% to 16.2% p = 1.1 x 10(-15)). Older age, farming occupations and foreign holidays were significantly associated with higher vitamin D in Orkney. Although mean vitamin D levels are higher in Orkney than mainland Scotland, this masks variation within the Orkney population which may influence MS risk

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Genome-wide analysis of epistasis in body mass index using multiple human populations

We surveyed gene–gene interactions (epistasis) in human body mass index (BMI) in four European populations (n<1200) via exhaustive pair-wise genome scans where interactions were computed as F ratios by testing a linear regression model fitting two single-nucleotide polymorphisms (SNPs) with interactions against the one without. Before the association tests, BMI was corrected for sex and age, normalised and adjusted for relatedness. Neither single SNPs nor SNP interactions were genome-wide significant in either cohort based on the consensus threshold (P=5.0E−08) and a Bonferroni corrected threshold (P=1.1E−12), respectively. Next we compared sub genome-wide significant SNP interactions (P<5.0E−08) across cohorts to identify common epistatic signals, where SNPs were annotated to genes to test for gene ontology (GO) enrichment. Among the epistatic genes contributing to the commonly enriched GO terms, 19 were shared across study cohorts of which 15 are previously published genome-wide association loci, including CDH13 (cadherin 13) associated with height and SORCS2 (sortilin-related VPS10 domain containing receptor 2) associated with circulating insulin-like growth factor 1 and binding protein 3. Interactions between the 19 shared epistatic genes and those involving BMI candidate loci (P<5.0E−08) were tested across cohorts and found eight replicated at the SNP level (P<0.05) in at least one cohort, which were further tested and showed limited replication in a separate European population (n>5000). We conclude that genome-wide analysis of epistasis in multiple populations is an effective approach to provide new insights into the genetic regulation of BMI but requires additional efforts to confirm the findings

Analysis of genome-wide DNA arrays reveals the genomic population structure and diversity in autochthonous Greek goat breeds

Goats play an important role in the livestock sector in Greece. The national herd consists mainly of two indigenous breeds, the Eghoria and Skopelos. Here, we report the population structure and genomic profiles of these two native goat breeds using Illumina's Goat SNP50 BeadChip. Moreover, we present a panel of candidate markers acquired using different genetic models for breed discrimination. Quality control on the initial dataset resulted in 48,841 SNPs kept for downstream analysis. Principal component and admixture analyses were applied to assess population structure. The rate of inbreeding within breed was evaluated based on the distribution of runs of homozygosity in the genome and respective coefficients, the genomic relationship matrix, the patterns of linkage disequilibrium, and the historic effective population size. Results showed that both breeds exhibit high levels of genetic diversity. Level of inbreeding between the two breeds estimated by the Wright's fixation index FST was low (Fst = 0.04362), indicating the existence of a weak genetic differentiation between them. In addition, grouping of farms according to their geographical locations was observed. This study presents for the first time a genome-based analysis on the genetic structure of the two indigenous Greek goat breeds and identifies markers that can be potentially exploited in future selective breeding programs for traceability purposes, targeted genetic improvement schemes and conservation strategies