Using haplotype differentiation among hierarchically structured populations for the detection of selection signatures

The detection of molecular signatures of selection is one of the major concerns of modern population genetics. A widely used strategy in this context is to compare samples from several populations, and to look for genomic regions with outstanding genetic differentiation between these populations. Genetic differentiation is generally based on allele frequency differences between populations, which are measured by Fst or related statistics. Here we introduce a new statistic, denoted hapFLK, which focuses instead on the differences of haplotype frequencies between populations. In contrast to most existing statistics, hapFLK accounts for the hierarchical structure of the sampled populations. Using computer simulations, we show that each of these two features - the use of haplotype information and of the hierarchical structure of populations - significantly improves the detection power of selected loci, and that combining them in the hapFLK statistic provides even greater power. We also show that hapFLK is robust with respect to bottlenecks and migration and improves over existing approaches in many situations. Finally, we apply hapFLK to a set of six sheep breeds from Northern Europe, and identify seven regions under selection, which include already reported regions but also several new ones. We propose a method to help identifying the population(s) under selection in a detected region, which reveals that in many of these regions selection most likely occurred in more than one population. Furthermore, several of the detected regions correspond to incomplete sweeps, where the favourable haplotype is only at intermediate frequency in the population(s) under selection

A high density recombination map of the pig reveals a correlation between sex-specific recombination and GC content

<p>Abstract</p> <p>Background</p> <p>The availability of a high-density SNP genotyping chip and a reference genome sequence of the pig (<it>Sus scrofa</it>) enabled the construction of a high-density linkage map. A high-density linkage map is an essential tool for further fine-mapping of quantitative trait loci (QTL) for a variety of traits in the pig and for a better understanding of mechanisms underlying genome evolution.</p> <p>Results</p> <p>Four different pig pedigrees were genotyped using the Illumina PorcineSNP60 BeadChip. Recombination maps for the autosomes were computed for each individual pedigree using a common set of markers. The resulting genetic maps comprised 38,599 SNPs, including 928 SNPs not positioned on a chromosome in the current assembly of the pig genome (build 10.2). The total genetic length varied according to the pedigree, from 1797 to 2149 cM. Female maps were longer than male maps, with a notable exception for SSC1 where male maps are characterized by a higher recombination rate than females in the region between 91–250 Mb. The recombination rates varied among chromosomes and along individual chromosomes, regions with high recombination rates tending to cluster close to the chromosome ends, irrespective of the position of the centromere. Correlations between main sequence features and recombination rates were investigated and significant correlations were obtained for all the studied motifs. Regions characterized by high recombination rates were enriched for specific GC-rich sequence motifs as compared to low recombinant regions. These correlations were higher in females than in males, and females were found to be more recombinant than males at regions where the GC content was greater than 0.4.</p> <p>Conclusions</p> <p>The analysis of the recombination rate along the pig genome highlighted that the regions exhibiting higher levels of recombination tend to cluster around the ends of the chromosomes irrespective of the location of the centromere. Major sex-differences in recombination were observed: females had a higher recombination rate within GC-rich regions and exhibited a stronger correlation between recombination rates and specific sequence features.</p

Imputation-Based Analysis of Association Studies: Candidate Regions and Quantitative Traits

We introduce a new framework for the analysis of association studies, designed to allow untyped variants to be more effectively and directly tested for association with a phenotype. The idea is to combine knowledge on patterns of correlation among SNPs (e.g., from the International HapMap project or resequencing data in a candidate region of interest) with genotype data at tag SNPs collected on a phenotyped study sample, to estimate (“impute”) unmeasured genotypes, and then assess association between the phenotype and these estimated genotypes. Compared with standard single-SNP tests, this approach results in increased power to detect association, even in cases in which the causal variant is typed, with the greatest gain occurring when multiple causal variants are present. It also provides more interpretable explanations for observed associations, including assessing, for each SNP, the strength of the evidence that it (rather than another correlated SNP) is causal. Although we focus on association studies with quantitative phenotype and a relatively restricted region (e.g., a candidate gene), the framework is applicable and computationally practical for whole genome association studies. Methods described here are implemented in a software package, Bim-Bam, available from the Stephens Lab website http://stephenslab.uchicago.edu/software.html

Биофизика зрительной сенсорной системы человека

Зрительная сенсорная система – это система, которая воспринимает излучение видимого спектра, после чего формируется изображение предметов окружающей среды в виде определенных ощущений (сенсорных чувств)

Selection Signatures in Worldwide Sheep Populations

[EN] The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environmentsSIThe authors have no support or funding to repor

An update of the goat genome assembly using dense radiation hybrid maps allows detailed analysis of evolutionary rearrangements in Bovidae

BACKGROUND: The domestic goat (Capra hircus), an important livestock species, belongs to a clade of Ruminantia, Bovidae, together with cattle, buffalo and sheep. The history of genome evolution and chromosomal rearrangements on a small scale in ruminants remain speculative. Recently completed goat genome sequence was released but is still in a draft stage. The draft sequence used a variety of assembly packages, as well as a radiation hybrid (RH) map of chromosome 1 as part of its validation. RESULTS: Using an improved RH mapping pipeline, whole-genome dense maps of 45,953 SNP markers were constructed with statistical confidence measures and the saturated maps provided a fine map resolution of approximate 65 kb. Linking RH maps to the goat sequences showed that the assemblies of scaffolds/super-scaffolds were globally accurate. However, we observed certain flaws linked to the process of anchoring chromosome using conserved synteny with cattle. Chromosome assignments, long-range order, and orientation of the scaffolds were reassessed in an updated genome sequence version. We also present new results exploiting the updated goat genome sequence to understand genomic rearrangements and chromosome evolution between mammals during species radiations. The sequence architecture of rearrangement sites between the goat and cattle genomes presented abundant segmental duplication on regions of goat chromosome 9 and 14, as well as new insertions in homologous cattle genome regions. This complex interplay between duplicated sequences and Robertsonian translocations highlights the rearrangement mechanism of centromeric nonallelic homologous recombination (NAHR) in mammals. We observed that species-specific shifts in ANKRD26 gene duplication are coincident with breakpoint reuse in divergent lineages and this gene family may play a role in chromosome stabilization in chromosome evolution. CONCLUSIONS: We generated dense maps of the complete whole goat genome. The chromosomal maps allowed us to anchor and orientate assembled genome scaffolds along the chromosomes, annotate chromosome rearrangements and thereby get a better understanding of the genome evolution of ruminants and other mammals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-625) contains supplementary material, which is available to authorized users

Selection Signatures in Worldwide Sheep Populations

The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Complex population structure and haplotype patterns in the Western European honey bee from sequencing a large panel of haploid drones

Honey bee subspecies originate from specific geographical areas in Africa, Europe and the Middle East, and beekeepers interested in specific phenotypes have imported genetic material to regions outside of the bees' original range for use either in pure lines or controlled crosses. Moreover, imported drones are present in the environment and mate naturally with queens from the local subspecies. The resulting admixture complicates population genetics analyses, and population stratification can be a major problem for association studies. To better understand Western European honey bee populations, we produced a whole genome sequence and single nucleotide polymorphism (SNP) genotype data set from 870 haploid drones and demonstrate its utility for the identification of nine genetic backgrounds and various degrees of admixture in a subset of 629 samples. Five backgrounds identified correspond to subspecies, two to isolated populations on islands and two to managed populations. We also highlight several large haplotype blocks, some of which coincide with the position of centromeres. The largest is 3.6 Mb long and represents 21% of chromosome 11, with two major haplotypes corresponding to the two dominant genetic backgrounds identified. This large naturally phased data set is available as a single vcf file that can now serve as a reference for subsequent populations genomics studies in the honey bee, such as (i) selecting individuals of verified homogeneous genetic backgrounds as references, (ii) imputing genotypes from a lower-density data set generated by an SNP-chip or by low-pass sequencing, or (iii) selecting SNPs compatible with the requirements of genotyping chips.This work was performed in collaboration with the GeT platform, Toulouse (France), a partner of the National Infrastructure France Génomique, thanks to support by the Commissariat aux Grands Invetissements (ANR-10-INBS-0009). Bioinformatics analyses were performed on the GenoToul Bioinfo computer cluster. This work was funded by a grant from the INRA Département de Génétique Animale (INRA Animal Genetics division) and by the SeqApiPop programme, funded by the FranceAgriMer grant 14-21-AT. We thank John Kefuss for helpful discussions. We thank Andrew Abrahams for providing honey bee samples from Colonsay (Scotland), the Association Conservatoire de l'Abeille Noire Bretonne (ACANB) for samples from Ouessant (France), CETA de Savoie for sample from Savoie, ADAPI for samples from Porquerolles and all beekeepers and bee breeders who kindly participated in this study by providing samples from their colonies.info:eu-repo/semantics/publishedVersio

Complex population structure and haplotype patterns in the Western European honey bee from sequencing a large panel of haploid drones:Sequencing haploid honey bee drones

International audienceHoney bee subspecies originate from specific geographical areas in Africa, Europe and the Middle East, and beekeepers interested in specific phenotypes have imported genetic material to regions outside of the bees' original range for use either in pure lines or controlled crosses. Moreover, imported drones are present in the environment and mate naturally with queens from the local subspecies. The resulting admixture complicates population genetics analyses, and population stratification can be a major problem for association studies. To better understand Western European honey bee populations, we produced a whole genome sequence and single nucleotide polymorphism (SNP) genotype data set from 870 haploid drones and demonstrate its utility for the identification of nine genetic backgrounds and various degrees of admixture in a subset of 629 samples. Five backgrounds identified correspond to subspecies, two to isolated populations on islands and two to managed populations. We also highlight several large haplotype blocks, some of which coincide with the position of centromeres. The largest is 3.6 Mb long and represents 21% of chromosome 11, with two major haplotypes corresponding to the two dominant genetic backgrounds identified. This large naturally phased data set is available as a single vcf file that can now serve as a reference for subsequent populations genomics studies in the honey bee, such as (i) selecting individuals of verified homogeneous genetic backgrounds as references, (ii) imputing genotypes from a lower-density data set generated by an SNP-chip or by low-pass sequencing, or (iii) selecting SNPs compatible with the requirements of genotyping chips