Genomic adaptation of admixed dairy cattle in East Africa

Dairy cattle in East Africa imported from the U.S. and Europe have been adapted to new environments. In small local farms, cattle have generally been maintained by cross breeding that could increase survivability under a severe environment. Eventually, genomic ancestry of a specific breed will be nearly fixed in genomic regions of local breeds or crossbreds when it is advantageous for survival or production in harsh environments. To examine this situation, 25 Friesians and 162 local cattle produced by crossbreeding of dairy breeds in Kenya were sampled and genotyped using 50K SNPs. Using principal componen tanalysis (PCA), the admixed local cattle were found to consist of several imported breeds, including Guernsey, Norwegian Red, and Holstein. To infer the influence of parental breeds on genomic regions, local ancestry mapping was performed based on the similarity of haplotypes. As a consequence, it appears that no genomic region has been under the complete influence of a specific parental breed. Nonetheless,the ancestry of Holstein-Friesians was substantial in most genomic regions (\u3e80%). Furthermore, we examined the frequency of the most common haplotypes from parental breeds that have changed substantially in Kenyan crossbreds during admixture. The frequency of these haplotypes from parental breeds, which were likely to be selected in temperate regions, has deviated considerably from expected frequency in 11 genomic regions.Additionally, extended haplotype homozygosity (EHH) based methods were applied to identify the regions responding to recent selectionin crossbreds, called candidate regions, resulting in seven regions that appeared to be affected by Holstein-Friesians. However, some signatures of selection were less dependent on Holsteins-Friesians, suggesting evidence of adaptation in East Africa. Thean alysis of local ancestry is a useful approach to understand the detailed genomic structure and may reveal regions of the genome required for specialized adaptation when combined with methods for searching for the recent changes of haplotype frequency in an admixed population

Identification of parental line specific effects of MLF2 on resistance to coccidiosis in chickens

<p>Abstract</p> <p>Background</p> <p><it>MLF2</it> was the candidate gene associated with coccidiosis resistance in chickens. Although single marker analysis supported the association between <it>MLF2</it> and coccidiosis resistance, causative mutation relevant to coccidiosis was not identified yet. Thus, this study suggested segregation analysis of <it>MLF2</it> haplotype and the association test of the other candidate genes using improved data transformation.</p> <p>Results</p> <p>A haplotype probably originated from one parental line was found out of 4 major haplotypes of <it>MLF2</it>. Frequency of this haplotype was 0.2 in parental chickens and its offspring in 12 families. Allele substitution effect of the <it>MLF2</it> haplotype originated from a specific line was associated with increased body weight and fecal egg count explaining coccidiosis resistance. Nevertheless Box-Cox transformation was able to improve normality; association test did not produce obvious different results compared with analysis with log transformed phenotype.</p> <p>Conclusion</p> <p>Allele substitution effect analysis and classification of <it>MLF2</it> haplotype identified the segregation of haplotype associated with coccidiosis resistance. The haplotype originated from a specific parental line was associated with improving disease resistance. Estimating effect of <it>MLF2</it> haplotype on coccidiosis resistance will provide useful information for selecting animals or lines for future study.</p

Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays

<p>Abstract</p> <p>Background</p> <p>Lipid metabolites and cytokines, including chemokines and growth factors, are the key regulators of immune cell function and differentiation, and thus, dysregulation of these regulators is associated with various human diseases. However, previous studies demonstrating a positive correlation of cytokine levels with aging may have been influenced by various environmental factors and underlying diseases. Also, data regarding cytokine profiling in the elderly are limited to a small subset of cytokines.</p> <p>Methods</p> <p>We compared the profiles of 22 cytokines, including chemokines and growth factors, in a case-controlled study group of a gender-matched, healthy cohort of 55 patients over the age of 65 and 55 patients under the age of 45. Assessment of serum cytokine concentrations was performed using commercially-available multiplex bead-based sandwich immunoassays.</p> <p>Results</p> <p>Soluble CD40 ligand (sCD40L) and transforming growth factor alpha (TGF-α) levels were significantly higher in the elderly patients, whereas granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly lower in the elderly patients. The partial correlation analysis demonstrating the correlation between cytokine levels when controlled for gender, systolic blood pressure, total cholesterol, HDL cholesterol, triglyceride, and serum creatinine levels further demonstrated that G-CSF, GM-CSF, and MCP-1 had significant negative correlations with age, whereas sCD40L and TGF-α had significant positive correlations.</p> <p>Conclusions</p> <p>Future studies will focus on examining the significance of these age-related changes in circulating cytokines and other biological markers and their potential contribution to the development of different age-associated diseases.</p

Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A

Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER) protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A) protein, which is a critical factor for HCV RNA replication, interacts with the IFN-beta-inducible protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore, the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall flow of autophagy; however, it is a substrate for autophagic degradation. The physical association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation. Altogether, our findings suggest that IFN-beta-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication.1110Ysciescopu

Signatures of Selection for Intramuscular Fat in Duroc Pigs

Intramuscular fat (IMF) content is an important trait affecting the quality of pork. Two Duroc populations (Iowa and Spain) selected for IMF were used to identify signatures of selection associated with IMF. The effects of selection were analyzed between two groups representing essentially select and control animals within each population using a discriminant analysis of principal components and Wright’s fixation index (FST) using 60k SNPs. Moreover, extended haplotype homozygosity-based approaches were used to examine the changes in haplotype frequency due to recent selection. New genomic regions have been identified by use of selection signatures and should provide useful information identification of genes involved in IMF and future selection

Identification of signatures of selection for intramuscular fat and backfat thickness in two Duroc populations

Intramuscular fat (IMF) content is an important trait affecting the quality of pork. Two Duroc populations, one under positive selection for IMF and the other selected for decreased backfat but under stabilizing selection for IMF, were used to identify signatures of selection associated with IMF using 60,000 single-nucleotide polymorphism data. The effects of selection were analyzed between 2 lines or groups representing selected and control animals within each population using a discriminant analysis of principal components and Wright’s fixation index (FST). Moreover, extended haplotype homozygosity-based approaches were used to examine the changes in haplotype frequency due to recent selection. Each statistical method identified 10–20 selection signatures. A few haplotype-based signatures of selection agreed with results from a genome-wide association study (GWAS), while FST measures showed a better agreement with GWAS results. Agreement of marker-trait associations and signatures of selection was limited, and further examination will be necessary to understand the effect of selection on IMF and why some regions identified by GWAS did not appear to respond to the selection practiced. The genes in 21 consensus selection signatures were examined. Several genes with an effect on overall fatness were identified, but further research is needed to assess whether or not some of them could have a specific effect on IMF

Genome-Wide Association Analyses of Biological Responses to Heat Stress in Pigs

With genetic selection for rapid, lean tissue accretion, pigs are becoming increasingly sensitive to heat stress (HS) due to their physiological limitations such as the lack of functional sweat glands to effectively dissipate heat. Increased respiration rate and reduced feed intake are immediate and conserved biological responses to HS in pigs and other livestock species. Genetic differences in how animals respond to high ambient temperatures have been previously reported, but genetic factors contributing to the response variability remain ill-defined. In this study, porcine high density single nucleotide polymorphism (SNP) beadchips were used to genotype 236 female pigs who had been exposed to HS conditions, and analyzed to detect chromosomal regions associated with biological responses measured before and after HS, including rectal temperature, respiration rate, feed intake, and body weight loss. We identified significant gene region associations for rectal temperature on SSC12, respiration rate on SSC14 and SSC16, as well as feed efficiency and weight loss on SSC13. Further analyses of these detected regions will likely reveal potential candidate genes and suggest molecular mechanisms contributing to the variability in the biological response of pigs to environmentally-induced hyperthermia