People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Going Coastal: Shared Evolutionary History between Coastal British Columbia and Southeast Alaska Wolves (Canis lupus)

Many coastal species occupying the temperate rainforests of the Pacific Northwest in North America comprise endemic populations genetically and ecologically distinct from interior continental conspecifics. Morphological variation previously identified among wolf populations resulted in recognition of multiple subspecies of wolves in the Pacific Northwest. Recently, separate genetic studies have identified diverged populations of wolves in coastal British Columbia and coastal Southeast Alaska, providing support for hypotheses of distinct coastal subspecies. These two regions are geographically and ecologically contiguous, however, there is no comprehensive analysis across all wolf populations in this coastal rainforest.By combining mitochondrial DNA datasets from throughout the Pacific Northwest, we examined the genetic relationship between coastal British Columbia and Southeast Alaska wolf populations and compared them with adjacent continental populations. Phylogenetic analysis indicates complete overlap in the genetic diversity of coastal British Columbia and Southeast Alaska wolves, but these populations are distinct from interior continental wolves. Analyses of molecular variation support the separation of all coastal wolves in a group divergent from continental populations, as predicted based on hypothesized subspecies designations. Two novel haplotypes also were uncovered in a newly assayed continental population of interior Alaska wolves.We found evidence that coastal wolves endemic to these temperate rainforests are diverged from neighbouring, interior continental wolves; a finding that necessitates new international strategies associated with the management of this species

Intraspecific Variation of the Aquatic Fungus Articulospora tetracladia: An Ubiquitous Perspective

The worldwide-distributed aquatic fungus Articulospora tetracladia Ingold is a dominant sporulating species in streams of the Northwest Iberian Peninsula. To elucidate the genetic diversity of A. tetracladia, we analyzed isolates collected from various types of plant litter or foam in streams from North and Central Portugal and North Spain, between 2000 and 2010. Genetic diversity of these fungal populations was assessed by denaturing gradient gel electrophoresis (DGGE) fingerprints and by using ITS1-5.8S-ITS2 barcodes. Moreover, ITS1-5.8S-ITS2 barcodes of A. tetracladia reported in other parts of the world (Central Europe, United Kingdom, Canada, Japan and Malaysia) were retrieved from the National Center for Biotechnology (NCBI) and the National Institute of Technology and Evaluation Biological Resource Center (NBRC) to probe into genetic diversity of A. tetracladia. PCR-DGGE of ITS2 region of 50 Iberian fungal isolates distinguished eight operational taxonomic units (OTUs), which were similar to those obtained from neighboring trees based on ITS2 gene sequences. On the other hand, ITS1-5.8S-ITS2 barcodes of 68 fungal isolates yielded nine OTUs, but five fungal isolates were not assigned to any of these OTUs. Molecular diversity was highest for OTU-8, which included only European isolates. Two haplotypes were observed within OTU-8 and OTU-9, while only one haplotype was found within each of the remaining OTUs. Malaysia did not share haplotypes with other countries. Overall results indicate that, apart from the Malaysian genotypes, A. tetracladia genotypes were geographically widespread irrespective of sampling time, sites or substrates. Furthermore, PCR-DGGE appeared to be a rapid tool for assessing intraspecific diversity of aquatic hyphomycetes

Research cardiac magnetic resonance imaging in end stage renal disease - incidence, significance and implications of unexpected incidental findings

Objectives: Left ventricular mass (LVM) at cardiac magnetic resonance imaging (CMR) is a frequent end point in clinical trials in nephrology. Trial participants with end stage renal disease (ESRD) may have a greater frequency of incidental findings (IF). We retrospectively investigated prevalence of IF in previous research CMR and reviewed their subsequent impact on participants. Methods: Between 2002 and 2006, 161 ESRD patients underwent CMR in a transplant assessment study. Images were used to assess LV mass and function. In the current study a radiologist reviewed the scans for IF. Review of patient records determined the subsequent clinical significance of IF. Results: There were 150 IF in 95 study participants. Eighty-four (56 %) were new diagnoses. One hundred and two were non-cardiac. Fifteen were suspicious of malignancy. There was a clinically significant IF for 14.9 % of the participants. In six cases earlier identification of an IF may have improved quality of life or survival. Conclusions: Without radiology support clinically important IF may be missed on CMR. Patients undergoing CMR in trials should be counselled about the frequency and implications of IF. Patients with ESRD have a higher prevalence of IF than reported in other populations. Nephrology studies require mechanisms for radiologist reporting and strategies for dealing with IF

Cognitive health among older adults in the United States and in England

<p>Abstract</p> <p>Background</p> <p>Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries.</p> <p>Methods</p> <p>Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87% for the HRS vs. 67% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale).</p> <p>Results</p> <p>US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment × country interaction).</p> <p>Conclusion</p> <p>Despite methodological differences in the administration of the surveys in the two countries, US adults aged ≥ 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.</p

Amplicon-Dependent CCNE1 Expression Is Critical for Clonogenic Survival after Cisplatin Treatment and Is Correlated with 20q11 Gain in Ovarian Cancer

Genomic amplification of 19q12 occurs in several cancer types including ovarian cancer where it is associated with primary treatment failure. We systematically attenuated expression of genes within the minimally defined 19q12 region in ovarian cell lines using short-interfering RNAs (siRNA) to identify driver oncogene(s) within the amplicon. Knockdown of CCNE1 resulted in G1/S phase arrest, reduced cell viability and apoptosis only in amplification-carrying cells. Although CCNE1 knockdown increased cisplatin resistance in short-term assays, clonogenic survival was inhibited after treatment. Gain of 20q11 was highly correlated with 19q12 amplification and spanned a 2.5 Mb region including TPX2, a centromeric protein required for mitotic spindle function. Expression of TPX2 was highly correlated with gene amplification and with CCNE1 expression in primary tumors. siRNA inhibition of TPX2 reduced cell viability but this effect was not amplicon-dependent. These findings demonstrate that CCNE1 is a key driver in the 19q12 amplicon required for survival and clonogenicity in cells with locus amplification. Co-amplification at 19q12 and 20q11 implies the presence of a cooperative mutational network. These observations have implications for the application of targeted therapies in CCNE1 dependent ovarian cancers

Two Evolutionary Histories in the Genome of Rice: the Roles of Domestication Genes

Genealogical patterns in different genomic regions may be different due to the joint influence of gene flow and selection. The existence of two subspecies of cultivated rice provides a unique opportunity for analyzing these effects during domestication. We chose 66 accessions from the three rice taxa (about 22 each from Oryza sativa indica, O. sativa japonica, and O. rufipogon) for whole-genome sequencing. In the search for the signature of selection, we focus on low diversity regions (LDRs) shared by both cultivars. We found that the genealogical histories of these overlapping LDRs are distinct from the genomic background. While indica and japonica genomes generally appear to be of independent origin, many overlapping LDRs may have originated only once, as a result of selection and subsequent introgression. Interestingly, many such LDRs contain only one candidate gene of rice domestication, and several known domestication genes have indeed been “rediscovered” by this approach. In summary, we identified 13 additional candidate genes of domestication

Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon

<p>Abstract</p> <p>Background</p> <p>Peru is one of the Latin American countries with the highest malaria burden, mainly due to <it>Plasmodium vivax </it>infections. However, little is known about <it>P. vivax </it>transmission dynamics in the Peruvian Amazon, where most malaria cases occur. The genetic diversity and population structure of <it>P. vivax </it>isolates collected in different communities around Iquitos city, the capital of the Peruvian Amazon, was determined.</p> <p>Methods</p> <p><it>Plasmodium vivax </it>population structure was determined by multilocus genotyping with 16 microsatellites on 159 <it>P. vivax </it>infected blood samples (mono-infections) collected in four sites around Iquitos city. The population characteristics were assessed only in samples with monoclonal infections (n = 94), and the genetic diversity was determined by calculating the expected heterozygosity and allelic richness. Both linkage disequilibrium and the genetic differentiation (<it>θ</it>) were estimated.</p> <p>Results</p> <p>The proportion of polyclonal infections varied substantially by site (11% - 70%), with the expected heterozygosity ranging between 0.44 and 0.69; no haplotypes were shared between the different populations. Linkage disequilibrium was present in all populations (<it>I</it>_A^S0.14 - 0.61) but was higher in those with fewer polyclonal infections, suggesting inbreeding and a clonal population structure. Strong population differentiation (<it>θ </it>= 0.45) was found and the Bayesian inference cluster analysis identified six clusters based on distinctive allele frequencies.</p> <p>Conclusion</p> <p>The <it>P. vivax </it>populations circulating in the Peruvian Amazon basin are genetically diverse, strongly differentiated and they have a low effective recombination rate. These results are in line with the low and clustered pattern of malaria transmission observed in the region around Iquitos city.</p

Varying Herbivore Population Structure Correlates with Lack of Local Adaptation in a Geographic Variable Plant-Herbivore Interaction

Local adaptation of parasites to their hosts due to coevolution is a central prediction of many theories in evolutionary biology. However, empirical studies looking for parasite local adaptation show great variation in outcomes, and the reasons for such variation are largely unknown. In a previous study, we showed adaptive differentiation in the arctiid moth Utetheisa ornatrix to its host plant, the pyrrolizidine alkaloid-bearing legume Crotalaria pallida, at the continental scale, but found no differentiation at the regional scale. In the present study, we sampled the same sites to investigate factors that may contribute to the lack of differentiation at the regional scale. We performed field observations that show that specialist and non-specialist polyphagous herbivore incidence varies among populations at both scales. With a series of common-garden experiments we show that some plant traits that may affect herbivory (pyrrolizidine alkaloids and extrafloral nectaries) vary at the regional scale, while other traits (trichomes and nitrogen content) just vary at the continental scale. These results, combined with our previous evidence for plant population differentiation based on larval performance on fresh fruits, suggest that U. ornatrix is subjected to divergent selection even at the regional scale. Finally, with a microsatellite study we investigated population structure of U. ornatrix. We found that population structure is not stable over time: we found population differentiation at the regional scale in the first year of sampling, but not in the second year. Unstable population structure of the herbivore is the most likely cause of the lack of regional adaptation