Associations of polymorphisms in TXNIP and gene–environment interactions with the risk of coronary artery disease in a Chinese Han population

Single nucleotide polymorphisms (SNPs) in thioredoxin‐interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two‐stage case–control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype ‘G‐T’ had a 1.22‐fold increased risk of CAD (P = 0.003). We also observed the cumulative effects of SNPs rs7212 and rs7211 on CAD risk and the severity of coronary atherosclerosis. Moreover, the gene–environment interactions among the variant genotypes of SNP rs7212, smoking habit, alcohol drinking habit and history of type 2 diabetes were associated with a 3.70‐fold increased risk of CAD (P < 0.001). Subsequent genotype‐phenotype correlation analyses further observed the significant effects of SNP rs7212 on TXNIP mRNA expression, plasma TXNIP and malondialdehyde levels. Taken together, our data suggest that TXNIP SNPs may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene–environment interactions.     

Feature selection and classification of protein–protein complexes based on their binding affinities using machine learning approaches

Protein–protein interactions are intrinsic to virtually every cellular process. Predicting the binding affinity of protein–protein complexes is one of the challenging problems in computational and molecular biology. In this work, we related sequence features of protein–protein complexes with their binding affinities using machine learning approaches. We set up a database of 185 protein–protein complexes for which the interacting pairs are heterodimers and their experimental binding affinities are available. On the other hand, we have developed a set of 610 features from the sequences of protein complexes and utilized Ranker search method, which is the combination of Attribute evaluator and Ranker method for selecting specific features. We have analyzed several machine learning algorithms to discriminate protein‐protein complexes into high and low affinity groups based on their K_d values. Our results showed a 10‐fold cross‐validation accuracy of 76.1% with the combination of nine features using support vector machines. Further, we observed accuracy of 83.3% on an independent test set of 30 complexes. We suggest that our method would serve as an effective tool for identifying the interacting partners in protein–protein interaction networks and human–pathogen interactions based on the strength of interactions. Proteins 2014; 82:2088–2096. © 2014 Wiley Periodicals, Inc.     

Evidence for the genetic basis and epistatic interactions underlying ocean‐ and river‐maturing ecotypes of Pacific Lamprey (Entosphenus tridentatus) returning to the Klamath River,California

Surveys of genomic variation have improved our understanding of the relationship between fitness‐related phenotypes and their underlying genetic basis. In some cases, single large‐effect genes have been found to underlie important traits; however, complex traits are expected to be under polygenic control and elucidation of multiple gene interactions may be required to fully understand the genetic basis of the trait. In this study, we investigated the genetic basis of the ocean‐ and river‐maturing ecotypes in anadromous Pacific lamprey (Entosphenus tridentatus). In Pacific lamprey, the ocean‐maturing ecotype is distinguished by advanced maturity of females (e.g., large egg mass) at the onset of freshwater migration relative to immature females of the river‐maturing ecotype. We examined a total of 219 adult Pacific lamprey that were collected at‐entry to the Klamath River over a 12‐month period. Each individual was genotyped at 308 SNPs representing known neutral and adaptive loci and measured at morphological traits, including egg mass as an indicator of ocean‐ and river‐maturing ecotype for females. The two ecotypes did not exhibit genetic structure at 148 neutral loci, indicating that ecotypic diversity exists within a single population. In contrast, we identified the genetic basis of maturation ecotypes in Pacific lamprey as polygenic, involving two unlinked gene regions that have a complex epistatic relationship. Importantly, these gene regions appear to show stronger effects when considered in gene interaction models than if just considered additive, illustrating the importance of considering epistatic effects and gene networks when researching the genetic basis of complex traits in Pacific lamprey and other species.     

Effect of different protein–energy ratio in pulse by-products and residue based pelleted feeds on growth, rumen fermentation, carcass and sausage quality in Barbari kids

Thirty two Barbari kids (5-month old of 10.62 ± 0.09 kg BW, 16 males and 16 females) were equally divided into four groups to monitor growth, nutrient utilization, rumen fermentation, blood metabolites, carcass traits, meat and sausage quality on diet based on Cajanus cajan straw (60) and concentrate mixture (40) to have different protein–energy ratio in the diets (Diet 1—CP 12%, TDN 55%, Diet 2—CP 12%, TDN 60%, Diet 3—CP 14%, TDN 55% and Diet 4—CP 14%, TDN 60%). The experimental kids in each group were fed the respective diets at 4% of their body weight and limited quantity (300–400 g/kid/day) of oat fodder. The average DM intake/kg W^0.75 during growth period was significantly (P < 0.05) higher in Diet 1 (low protein–low energy) than Diet 4 (high protein–high energy). Kids under Diet 2 (low protein–high energy) and Diet 4 (high protein–high energy) gained 7.2% and 14.5% more weight respectively per day compared to those on Diet 1 (low protein–low energy), however, values of final body weight, average daily gain and feed conversion efficiency (%) were not significantly different (P > 0.05). The pH and total VFA concentration in the rumen liquor were similar (P > 0.05) among the four treatment groups. TCA precipitable-N was insignificantly (P > 0.05) higher in Diet 4 than other diets. Glucose, urea–nitrogen, total protein, albumin and globulin concentration in plasma were unaffected by treatments. TDN intake, DCP and TDN percentages were also similar (P > 0.05) among the four groups. Nitrogen balance (g/day/kid) values also showed no significant variation. Dietary effect was also not significant (P > 0.05) in the values of hot carcass weight, dressing percentage, carcass physical composition, variety meat yield and fat deposition but not breast fat thickness and kidney fat accumulation, which were significantly (P < 0.05) higher in Diet 2. Chemical composition values of Longissimus thoracis muscle were similar (P > 0.05) in percentage moisture, fat and ash, while CP was significantly (P < 0.05) higher in Diets 2 and 3 than Diets 1 and 4. There were no significant differences (P > 0.05) in the chemical composition of sausages prepared using meat from the kids of different treatments. Therefore, it may be concluded that pelleted feed of Diet 2 responded with better growth rate, quality of carcass traits and meat quality.