Recombinational landscape of porcine X chromosome and individual variation in female meiotic recombination associated with haplotypes of Chinese pigs

<p>Abstract</p> <p>Background</p> <p>Variations in recombination fraction (θ) among chromosomal regions, individuals and families have been observed and have an important impact on quantitative trait loci (QTL) mapping studies. Such variations on porcine chromosome X (SSC-X) and on other mammalian chromosome X are rarely explored. The emerging assembly of pig sequence provides exact physical location of many markers, facilitating the study of a fine-scale recombination landscape of the pig genome by comparing a clone-based physical map to a genetic map. Using large offspring of F₁females from two large-scale resource populations (Large White ♂ × Chinese Meishan ♀, and White Duroc ♂ × Chinese Erhualian ♀), we were able to evaluate the heterogeneity in θ for a specific interval among individual F₁females.</p> <p>Results</p> <p>Alignments between the cytogenetic map, radiation hybrid (RH) map, genetic maps and clone map of SSC-X with the physical map of human chromosome X (HSA-X) are presented. The most likely order of 60 markers on SSC-X is inferred. The average recombination rate across SSC-X is of ~1.27 cM/Mb. However, almost no recombination occurred in a large region of ~31 Mb extending from the centromere to Xq21, whereas in the surrounding regions and in the Xq telomeric region a recombination rate of 2.8-3.3 cM/Mb was observed, more than twice the chromosome-wide average rate. Significant differences in θ among F₁females within each population were observed for several chromosomal intervals. The largest variation was observed in both populations in the interval <it>UMNP71-SW1943</it>, or more precisely in the subinterval <it>UMNP891-UMNP93</it>. The individual variation in θ over this subinterval was found associated with F₁females' maternal haplotypes (Chinese pig haplotypes) and independent of paternal haplotype (European pig haplotypes). The θ between <it>UMNP891 </it>and <it>UMNP93 </it>for haplotype 1122 and 4311 differed by more than fourteen-fold (10.3% vs. 0.7%).</p> <p>Conclusions</p> <p>This study reveals marked regional, individual and haplotype-specific differences in recombination rate on SSC-X. Lack of recombination in such a large region makes it impossible to narrow QTL interval using traditional fine-mapping approaches. The relationship between recombination variation and haplotype polymorphism is shown for the first time in pigs.</p

Evolutionary Characterization of the Pandemic H1N1/ 2009 Influenza Virus in Humans Based on Non-Structural Genes

The 2009 influenza pandemic had a tremendous social and economic impact. To study the genetic diversity and evolution of the 2009 H1N1 virus, a mutation network for the non-structural (NS) gene of the virus was constructed. Strains of the 2009 H1N1 pandemic influenza A virus could be divided into two categories based on the V123I mutation in the NS1 gene: G1 (characterized as 123 Val) and G2 (characterized as 123 Ile). Sequence homology analysis indicated that one type of NS sequence, primarily isolated from Mexico, was likely the original type in this pandemic. The two genotypes of the virus presented distinctive clustering features in their geographic distributions. These results provide additional insight into the genetics and evolution of human pandemic influenza H1N1

Frailty in hypertensive population and its association with all-cause mortality: data from the National Health and Nutrition Examination Survey

ObjectivesThis study aimed to investigate the relationship between frailty and all-cause mortality in hypertensive population.MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002 and mortality data from the National Death Index. Frailty was assessed using the revised version of the Fried frailty criteria (weakness, exhaustion, low physical activity, shrinking, and slowness). This study aimed to evaluate the association between frailty and all-cause mortality. Cox proportional hazard models were used to evaluate the association between frailty category and all-cause mortality, adjusted for age, sex, race, education, poverty–income ratio, smoking, alcohol, diabetes, arthritis, congestive heart failure, coronary heart disease, stroke, overweight, cancer or malignancy, chronic obstructive pulmonary disease, chronic kidney disease, and taking medicine for hypertension.ResultsWe gathered data of 2,117 participants with hypertension; 17.81%, 28.77%, and 53.42% were classified as frail, pre-frail, and robust, respectively. We found that frail [hazard ratio (HR) = 2.76, 95% confidence interval (CI) = 2.33–3.27] and pre-frail (HR = 1.38, 95% CI = 1.19–1.59] were significantly associated with all-cause mortality after controlling for variables. We found that frail (HR = 3.02, 95% CI = 2.50–3.65) and pre-frail (HR = 1.35, 95% CI = 1.15–1.58) were associated with all-cause mortality in the age group ≥65 years. For the frailty components, weakness (HR = 1.77, 95% CI = 1.55–2.03), exhaustion (HR = 2.25, 95% CI = 1.92–2.65), low physical activity (HR = 2.25, 95% CI = 1.95–2.61), shrinking (HR = 1.48, 95% CI = 1.13–1.92), and slowness (HR = 1.44, 95% CI = 1.22–1.69) were associated with all-cause mortality.ConclusionThis study demonstrated that frailty and pre-frailty were associated with an increased risk of all-cause mortality in patients with hypertension. More attention should be paid to frailty in hypertensive patients, and interventions to reduce the burden of frailty may improve outcomes in these patients

A Missense Mutation in PPARD Causes a Major QTL Effect on Ear Size in Pigs

Chinese Erhualian is the most prolific pig breed in the world. The breed exhibits exceptionally large and floppy ears. To identify genes underlying this typical feature, we previously performed a genome scan in a large scale White Duroc × Erhualian cross and mapped a major QTL for ear size to a 2-cM region on chromosome 7. We herein performed an identical-by-descent analysis that defined the QTL within a 750-kb region. Historically, the large-ear feature has been selected for the ancient sacrificial culture in Erhualian pigs. By using a selective sweep analysis, we then refined the critical region to a 630-kb interval containing 9 annotated genes. Four of the 9 genes are expressed in ear tissues of piglets. Of the 4 genes, PPARD stood out as the strongest candidate gene for its established role in skin homeostasis, cartilage development, and fat metabolism. No differential expression of PPARD was found in ear tissues at different growth stages between large-eared Erhualian and small-eared Duroc pigs. We further screened coding sequence variants in the PPARD gene and identified only one missense mutation (G32E) in a conserved functionally important domain. The protein-altering mutation showed perfect concordance (100%) with the QTL genotypes of all 19 founder animals segregating in the White Duroc × Erhualian cross and occurred at high frequencies exclusively in Chinese large-eared breeds. Moreover, the mutation is of functional significance; it mediates down-regulation of β-catenin and its target gene expression that is crucial for fat deposition in skin. Furthermore, the mutation was significantly associated with ear size across the experimental cross and diverse outbred populations. A worldwide survey of haplotype diversity revealed that the mutation event is of Chinese origin, likely after domestication. Taken together, we provide evidence that PPARD G32E is the variation underlying this major QTL

Influence of paste thickness on the coated aggregates on properties of high-density sulphoaluminate cement concrete

An improved method for the densified mixture design algorithm and Fuller curve were used to design high-density sulphoaluminate cement concrete (HDSC). The performance of HDSC is significantly influenced by the paste thickness on the coated aggregates. Sulphoaluminate cement concrete mixtures containing aggregates coated with 3 different paste thickness of t=10μm, 20μm, and 30μm and water-binder ratios (W/B) of 0.25, 0.30 and 0.35 were prepared. The results of experiments show that paste thickness on the coated aggregates significantly influences the mechanical properties and durability of HDSC. With the increase of paste thickness, the compressive strength is increased, but the electrical resistivity is decreased, particularly at the early ages of 1 and 3 days. The sulfate corrosion resistance coefficients of HDSC are larger than 1.0, the total porosity can be less than 7%, and the micropore (i.e. with pore size less than 20nm) can be larger than 70%

Using MOPSO for Optimizing Randomized Response Schemes in Privacy Computing

It is a challenging concern in data collecting, publishing, and mining when personal information is controlled by untrustworthy cloud services with unpredictable risks for privacy leakages. In this paper, we formulate an information-theoretic model for privacy protection and present a concrete solution to theoretical architecture in privacy computing from the perspectives of quantification and optimization. Thereinto, metrics of privacy and utility for randomized response (RR) which satisfy differential privacy are derived as average mutual information and average distortion rate under the information-theoretic model. Finally, a discrete multiobjective particle swarm optimization (MOPSO) is proposed to search optimal RR distorted matrices. To the best of our knowledge, our proposed approach is the first solution to optimize RR distorted matrices using discrete MOPSO. In detail, particles’ position and velocity are redefined in the problem-guided initialization and velocity updating mechanism. Two mutation strategies are introduced to escape from local optimum. The experimental results illustrate that our approach outperforms existing state-of-the-art works and can contribute optimal Pareto solutions of extensive RR schemes to future study

The G32E functional variant reduces activity of PPARD by nuclear export and post-translational modification in pigs.

Peroxisome proliferator-activated receptor beta/delta (PPARD) is a crucial and multifaceted determinant of diverse biological functions including lipid metabolism, embryonic development, inflammatory response, wound healing and cancer. Recently, we proposed a novel function of porcine PPARD (sPPARD) in external ear development. A missense mutation (G32E) in an evolutionary conservative domain of sPPARD remarkably increases external ear size in pigs. Here, we investigated the underlying molecular mechanism of the causal mutation at the cellular level. Using a luciferase reporter system, we showed that the G32E substitution reduced transcription activity of sPPARD in a ligand-dependent manner. By comparison of the subcellular localization of wild-type and mutated sPPARD in both PK-15 cells and pinna cartilage-derived primary chondrocytes, we found that the G32E substitution promoted CRM-1 mediated nuclear exportation of sPPARD. With the surface plasmon resonance technology, we further revealed that the G32E substitution had negligible effect on its ligand binding affinity. Finally, we used co-immunoprecipitation and luciferase reporter assays to show that the G32E substitution greatly reduced ubiquitination level by blocking ubiquitination of the crucial A/B domain and consequently decreased transcription activity of sPPARD. Taken together, our findings strongly support that G32E is a functional variant that plays a key role in biological activity of sPPARD, which advances our understanding of the underlying mechanism of sPPARD G32E for ear size in pigs

Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'-Untranslated Region.

Sex determining region Y-box 9 (SOX9) is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18 bp indel had been detected in the 5'-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18) between position +247 bp and +266 bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR harbours a highly conserved cAMP-response element (CRE) half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK-15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18 bp segment. Hence, the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'-UTR is of functional importance and may therefore indeed be a causative variation in SOX9 associated traits