Effect of a Co-Feed Liquid Whey-Integrated Diet on Crossbred Pigs' Fecal Microbiota.

This study assessed the potential effect of a co-feed liquid whey-integrated diet on the fecal microbiota of 14 crossbred pigs. The experimental design was as follows: seven pigs were in the control group, fed with a control feed, and seven were in the experimental group, fed with the same control feed supplemented daily with liquid whey. The collection of fecal samples was conducted on each animal before the dietary treatment (T0) and one (T1), and two (T2) months after the beginning of the co-feed integration. In addition, blood samples were collected from each pig at the same time points in order to evaluate the physiological parameters. Taxonomic analysis showed a bacterial community dominated by Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria phyla that populated the crossbred pig feces. The diversity metrics suggested that the co-feed supplementation affected some alpha diversity indexes of the fecal microbiota. In addition, the differential abundance analysis at the genus level revealed significant differences for various genera, suggesting that the liquid whey supplementation potentially influenced a part of the bacterial community over time. Spearman's correlations revealed that the differential abundant genera identified are positively or negatively correlated with the physiological parameters.

Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle.

The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10-7 and p < 1.89 × 10-7, respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens.

Exploring the value of genomic predictions to simultaneously improve production potential and resilience of farmed animals.

Sustainable livestock production requires that animals have a high production potential but are also highly resilient to environmental challenges. The first step to simultaneously improve these traits through genetic selection is to accurately predict their genetic merit. In this paper, we used simulations of sheep populations to assess the effect of genomic data, different genetic evaluation models and phenotyping strategies on prediction accuracies and bias for production potential and resilience. In addition, we also assessed the effect of different selection strategies on the improvement of these traits. Results show that estimation of both traits greatly benefits from taking repeated measurements and from using genomic information. However, the prediction accuracy for production potential is compromised, and resilience estimates tends to be upwards biased, when families are clustered in groups even when genomic information is used. The prediction accuracy was also found to be lower for both traits, resilience and production potential, when the environment challenge levels are unknown. Nevertheless, we observe that genetic gain in both traits can be achieved even in the case of unknown environmental challenge, when families are distributed across a large range of environments. Simultaneous genetic improvement in both traits however greatly benefits from the use of genomic evaluation, reaction norm models and phenotyping in a wide range of environments. Using models without the reaction norm in scenarios where there is a trade-off between resilience and production potential, and phenotypes are collected from a narrow range of environments may result in a loss for one trait. The study demonstrates that genomic selection coupled with reaction-norm models offers great opportunities to simultaneously improve productivity and resilience of farmed animals even in the case of a trade-off.

Effect of preoperative biliary stent on postoperative complications after pancreaticoduodenectomy for cancer: Neoadjuvant versus upfront treatment.

BACKGROUND: Limited data are available regarding the effect of preoperative biliary stent, during long-course neoadjuvant chemotherapy, on postoperative complications. The aim of the study is to analyze whether the association of neoadjuvant chemotherapy and biliary stent increases overall and infectious complications after pancreaticoduodenectomy. METHODS: Data for 538 consecutive pancreatic ductal adenocarcinoma patients who underwent pancreaticoduodenectomy between 2015 and 2020 were retrospectively analyzed. Four groups of patients were identified: neoadjuvant chemotherapy + biliary stent (171 patients), neoadjuvant chemotherapy-no biliary stent (65 patients), upfront surgery + biliary stent (184 patients), and upfront surgery-no biliary stent (118 patients). Median neoadjuvant chemotherapy duration was 6 months. The main outcome of the study was the occurrence of postoperative infections. RESULTS: No differences among the 4 groups were observed for pancreaticoduodenectomy-specific complications (ie, POPF, DGE, PPH). Infectious complications, in particular surgical site infections, were more frequent in neoadjuvant chemotherapy + biliary stent group (P = 0.001). At multivariate analysis, biliary stent was significantly associated with postoperative infectious complications in the overall cohort (odds ratio 1.996, confidence interval 95% 1.29-3.09, P = .002) and in neoadjuvant chemotherapy patients (odds ratio 5.974, 95% confidence interval 2.52-14.13, P < .001). Biliary stent significantly increased the comprehensive complication index by 9.5% (95% confidence interval 0.04-0.64, P = 0.024) in the overall cohort and 18.9% (95% confidence interval 0.22-1.23, P = .005) in the neoadjuvant chemotherapy group. The presence of multidrug-resistant microorganisms in intraoperative bile culture was not influenced by long-course neoadjuvant chemotherapy. CONCLUSION: In neoadjuvant chemotherapy patients, biliary stent increased the occurrence of postoperative infectious complications and surgical site infections, while the incidence of multidrug-resistant bacteria in intraoperative bile culture was similar between groups.

Assessment of genotyping array performance for genome-wide association studies and imputation in African cattle.

BACKGROUND: In cattle, genome-wide association studies (GWAS) have largely focused on European or Asian breeds, using genotyping arrays that were primarily designed for European cattle. Because there is growing interest in performing GWAS in African breeds, we have assessed the performance of 23 commercial bovine genotyping arrays for capturing the diversity across African breeds and performing imputation. We used 409 whole-genome sequences (WGS) spanning global cattle breeds, and a real cohort of 2481 individuals (including African breeds) that were genotyped with the Illumina high-density (HD) array and the GeneSeek bovine 50 k array. RESULTS: We found that commercially available arrays were not effective in capturing variants that segregate among African indicine animals. Only 6% of these variants in high linkage disequilibrium (LD) (r2 > 0.8) were on the best performing arrays, which contrasts with the 17% and 25% in African and European taurine cattle, respectively. However, imputation from available HD arrays can successfully capture most variants (accuracies up to 0.93), mainly when using a global, not continent-specific, reference panel, which partially reflects the unusually high levels of admixture on the continent. When considering functional variants, the GGPF250 array performed best for tagging WGS variants and imputation. Finally, we show that imputation from low-density arrays can perform almost as well as HD arrays, if a two-stage imputation approach is adopted, i.e. first imputing to HD and then to WGS, which can potentially reduce the costs of GWAS. CONCLUSIONS: Our results show that the choice of an array should be based on a balance between the objective of the study and the breed/population considered, with the HD and BOS1 arrays being the best choice for both taurine and indicine breeds when performing GWAS, and the GGPF250 being preferable for fine-mapping studies. Moreover, our results suggest that there is no advantage to using the indicus-specific arrays for indicus breeds, regardless of the objective. Finally, we show that using a reference panel that better represents global bovine diversity improves imputation accuracy, particularly for non-European taurine populations.

Effect of genotyping strategies on the sustained benefit of single-step genomic BLUP over multiple generations.

BACKGROUND: Single-step genomic best linear unbiased prediction (ssGBLUP) allows the inclusion of information from genotyped and ungenotyped individuals in a single analysis. This avoids the need to genotype all candidates with the potential benefit of reducing overall costs. The aim of this study was to assess the effect of genotyping strategies, the proportion of genotyped candidates and the genotyping criterion to rank candidates to be genotyped, when using ssGBLUP evaluation. A simulation study was carried out assuming selection over several discrete generations where a proportion of the candidates were genotyped and evaluation was done using ssGBLUP. The scenarios compared were: (i) three genotyping strategies defined by their protocol for choosing candidates to be genotyped (RANDOM: candidates were chosen at random; TOP: candidates with the best genotyping criterion were genotyped; and EXTREME: candidates with the best and worse criterion were genotyped); (ii) eight proportions of genotyped candidates (p); and (iii) two genotyping criteria to rank candidates to be genotyped (candidates' own phenotype or estimated breeding values). The criteria of the comparison were the cumulated gain and reliability of the genomic estimated breeding values (GEBV). RESULTS: The genotyping strategy with the greatest cumulated gain was TOP followed by RANDOM, with EXTREME behaving as RANDOM at low p and as TOP with high p. However, the reliability of GEBV was higher with RANDOM than with TOP. This disparity between the trend of the gain and the reliability is due to the TOP scheme genotyping the candidates with the greater chances of being selected. The extra gain obtained with TOP increases when the accuracy of the selection criterion to rank candidates to be genotyped increases. CONCLUSIONS: The best strategy to maximise genetic gain when only a proportion of the candidates are to be genotyped is TOP, since it prioritises the genotyping of candidates which are more likely to be selected. However, the strategy with the greatest GEBV reliability does not achieve the largest gain, thus reliability cannot be considered as an absolute and sufficient criterion for determining the scheme which maximises genetic gain.

Multiple Country and Breed Genomic Prediction of Tick Resistance in Beef Cattle.

Ticks cause substantial production losses for beef and dairy cattle. Cattle resistance to ticks is one of the most important factors affecting tick control, but largely neglected due to the challenge of phenotyping. In this study, we evaluate the pooling of tick resistance phenotyped reference populations from multi-country beef cattle breeds to assess the possibility of improving host resistance through multi-trait genomic selection. Data consisted of tick counts or scores assessing the number of female ticks at least 4.5 mm length and derived from seven populations, with breed, country, number of records and genotyped/phenotyped animals being respectively: Angus (AN), Brazil, 2,263, 921/1,156, Hereford (HH), Brazil, 6,615, 1,910/2,802, Brangus (BN), Brazil, 2,441, 851/851, Braford (BO), Brazil, 9,523, 3,062/4,095, Tropical Composite (TC), Australia, 229, 229/229, Brahman (BR), Australia, 675, 675/675, and Nguni (NG), South Africa, 490, 490/490. All populations were genotyped using medium density Illumina SNP BeadChips and imputed to a common high-density panel of 332,468 markers. The mean linkage disequilibrium (LD) between adjacent SNPs varied from 0.24 to 0.37 across populations and so was sufficient to allow genomic breeding values (GEBV) prediction. Correlations of LD phase between breeds were higher between composites and their founder breeds (0.81 to 0.95) and lower between NG and the other breeds (0.27 and 0.35). There was wide range of estimated heritability (0.05 and 0.42) and genetic correlation (-0.01 and 0.87) for tick resistance across the studied populations, with the largest genetic correlation observed between BN and BO. Predictive ability was improved under the old-young validation for three of the seven populations using a multi-trait approach compared to a single trait within-population prediction, while whole and partial data GEBV correlations increased in all cases, with relative improvements ranging from 3% for BO to 64% for TC. Moreover, the multi-trait analysis was useful to correct typical over-dispersion of the GEBV. Results from this study indicate that a joint genomic evaluation of AN, HH, BN, BO and BR can be readily implemented to improve tick resistance of these populations using selection on GEBV. For NG and TC additional phenotyping will be required to obtain accurate GEBV.

Detection of genomic regions underlying milk production traits in Valle del Belice dairy sheep using regional heritability mapping.

The aim of this study was to identify genomic regions underlying milk production traits in the Valle del Belice dairy sheep using regional heritability mapping (RHM). Repeated measurements for milk yield (MY), fat percentage and yield (F% and FY) and protein percentage and yield (P% and PY), collected over a period of 6 years (2006-2012) on 481 Valle del Belice ewes, were used for the analysis. Animals were genotyped with the Illumina 50k SNP chip. Variance components, heritabilities and repeatabilities within and across lactations were estimated, fitting parity, litter size, season of lambing and fortnights in milk, as fixed; and additive genetic, permanent environment within and across lactations, flock by test-day interaction and residual as random effects. For the RHM analysis, the model included the same fixed and random effects as before, plus an additional regional genomic additive effect (specific for the region being tested) as random. While the whole genomic additive effect was estimated using the genomic relationship matrix (GRM) constructed from all SNPs, the regional genomic additive effect was estimated from a GRM matrix constructed from the SNPs within each region. Heritability estimates ranged between 0.06 and 0.15, with repeatabilities being between 0.14 and 0.24 across lactations and between 0.23 and 0.39 within lactation for all milk production traits. A substantial effect of flock-test-day on milk production traits was also estimated. Significant genomic regions at either genome-wide (p < .05) or suggestive (i.e., one false positive per genome scan) level were identified on chromosome (OAR) 2, 3 and 20 for F% and on OAR3 for P%, with the regions on OAR3 in common between the two traits. Our results confirmed the role of LALBA and AQP genes, on OAR3, as candidate genes for milk production traits in sheep.

4K ultra HD technology reduces operative time and intraoperative blood loss in colorectal laparoscopic surgery.

Background: HD systems are routinely used in laparoscopic surgery, 4K ultra HD monitors are mainly available within specialized, high-volume laparoscopic centers. The higher resolution of 4K ultra HD video could upgrade the surgical performance improving intraoperative and post-operative outcomes. Methods: We performed a retrospective comparative analysis of intraoperative parameters and post-operative outcomes in a cohort of patients operated on for elective laparoscopic procedures for colo-rectal cancer during two different time frames: 2017 procedures performed using the Visera Elite full HD technology (® Olympus America, Medical) and the 2018 procedures performed the Visera 4K Ultra HD System (® Olympus America, Medical). Results: There was a statistically significant reduction in operative time in patients operated on with the 4K ultra HD technology compared to HD technology (p < 0.05). Intraoperative blood loss was significantly reduced in patients operated in 2018 (p < 0.05). There were no statistically significant differences in complication rate and postoperative outcomes between the two groups.

Symptomatic Uncomplicated Diverticular Disease and Incidence of Unexpected Abscess during Sigmoidectomy: A Multicenter Prospective Observational Study.

BACKGROUND: Symptomatic uncomplicated diverticular disease can affect patients' everyday routine. Considerable efforts have been made to identify clinical features that correlate to the severity of the disease. Unexpected intraoperative abscesses are reported in large retrospective series, showing how uncomplicated symptoms and presentations can underlie a complicated disease. The aim of this study was to investigate the incidence of pericolic or intramural abscess in patients undergoing elective sigmoidectomy for symptomatic uncomplicated diverticular disease and see if chronic symptoms correlate to the presence of an abscess. METHODS: Between January 2016 and June 2018, we prospectively collected data of patients who were given indication to elective sigmoidectomy for symptomatic uncomplicated diverticular disease. Patients were divided into 3 groups: acute resolving, smoldering, and atypical according to a previously described classification of uncomplicated diverticular disease. RESULTS: One hundred fifty-eight consecutive patients were enrolled in the study. The median age was 63 years (22- 88), and the mean body mass index was 26 (±7) kg/m2. There were 114 patients in the acute resolving group, 36 in the smoldering group, and 8 in the atypical group. An unexpected abscess was reported in 75 patients (47.5%) during surgery or pathological examination. The incidence of -abscess was greater for patient in the smoldering group (p = 0.0243). CONCLUSION: Our series of patients affected by symptomatic uncomplicated diverticular disease showed an incidence of unexpected pericolic or intramural abscess of 47.5%. Patients affected by smoldering diverticular disease presented a greater abscess rate.

Balancing selection at a premature stop mutation in the myostatin gene underlies a recessive leg weakness syndrome in pigs.

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation causing a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species. The MSTN mutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, the MSTN mutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage (allele frequency, q = 0.22). Knockout of the porcine MSTN by gene editing has previously been linked to problems of low piglet survival and lameness. This MSTN mutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth.

Dissecting the Genomic Architecture of Resistance to Eimeria maxima Parasitism in the Chicken.

Coccidiosis in poultry, caused by protozoan parasites of the genus Eimeria, is an intestinal disease with substantial economic impact. With the use of anticoccidial drugs under public and political pressure, and the comparatively higher cost of live-attenuated vaccines, an attractive complementary strategy for control is to breed chickens with increased resistance to Eimeria parasitism. Prior infection with Eimeria maxima leads to complete immunity against challenge with homologous strains, but only partial resistance to challenge with antigenically diverse heterologous strains. We investigate the genetic architecture of avian resistance to E. maxima primary infection and heterologous strain secondary challenge using White Leghorn populations of derived inbred lines, C.B12 and 15I, known to differ in susceptibility to the parasite. An intercross population was infected with E. maxima Houghton (H) strain, followed 3 weeks later by E. maxima Weybridge (W) strain challenge, while a backcross population received a single E. maxima W infection. The phenotypes measured were parasite replication (counting fecal oocyst output or qPCR for parasite numbers in intestinal tissue), intestinal lesion score (gross pathology, scale 0-4), and for the backcross only, serum interleukin-10 (IL-10) levels. Birds were genotyped using a high density genome-wide DNA array (600K, Affymetrix). Genome-wide association study located associations on chromosomes 1, 2, 3, and 5 following primary infection in the backcross population, and a suggestive association on chromosome 1 following heterologous E. maxima W challenge in the intercross population. This mapped several megabases away from the quantitative trait locus (QTL) linked to the backcross primary W strain infection, suggesting different underlying mechanisms for the primary- and heterologous secondary- responses. Underlying pathways for those genes located in the respective QTL for resistance to primary infection and protection against heterologous challenge were related mainly to immune response, with IL-10 signaling in the backcross primary infection being the most significant. Additionally, the identified markers associated with IL-10 levels exhibited significant additive genetic variance. We suggest this is a phenotype of interest to the outcome of challenge, being scalable in live birds and negating the requirement for single-bird cages, fecal oocyst counts, or slaughter for sampling (qPCR).

Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis.

BACKGROUND: Coccidiosis is a major contributor to losses in poultry production. With emerging constraints on the use of in-feed prophylactic anticoccidial drugs and the relatively high costs of effective vaccines, there are commercial incentives to breed chickens with greater resistance to this important production disease. To identify phenotypic biomarkers that are associated with the production impacts of coccidiosis, and to assess their covariance and heritability, 942 Cobb500 commercial broilers were subjected to a defined challenge with Eimeria tenella (Houghton). Three traits were measured: weight gain (WG) during the period of infection, caecal lesion score (CLS) post mortem, and the level of a serum biomarker of intestinal inflammation, i.e. circulating interleukin 10 (IL-10), measured at the height of the infection. RESULTS: Phenotypic analysis of the challenged chicken cohort revealed a significant positive correlation between CLS and IL-10, with significant negative correlations of both these traits with WG. Eigenanalysis of phenotypic covariances between measured traits revealed three distinct eigenvectors. Trait weightings of the first eigenvector, (EV1, eigenvalue = 59%), were biologically interpreted as representing a response of birds that were susceptible to infection, with low WG, high CLS and high IL-10. Similarly, the second eigenvector represented infection resilience/resistance (EV2, 22%; high WG, low CLS and high IL-10), and the third eigenvector tolerance (EV3, 19%; high WG, high CLS and low IL-10), respectively. Genome-wide association studies (GWAS) identified two SNPs that were associated with WG at the suggestive level. CONCLUSIONS: Eigenanalysis separated the phenotypic impact of a defined challenge with E. tenella on WG, caecal inflammation/pathology, and production of IL-10 into three major eigenvectors, indicating that the susceptibility-resistance axis is not a single continuous quantitative trait. The SNPs identified by the GWAS for body weight were located in close proximity to two genes that are involved in innate immunity (FAM96B and RRAD).

Amyand Hernia in an elderly patient.

INTRODUCTION: Inguinal hernia is one of the most common surgical entities and often poses technical dilemmas, even for the experienced surgeon. Amyand's hernia is an inguinal hernia; a protrusion of abdominal cavity content through the inguinal canal, with a vermiform appendix. CASE REPORT: A 77 years old Caucasian male was referred to our institution for the evaluation of a recurrent right inguinal hernia. During the surgery, we discovered a rare type I Amyand hernia. Following the guidelines we performed, a prosthetic tension-free inguinal ernioplasty without appendectomy.The patient was discharged on the first post-operative day. The follow-up at 7 days was uneventful. DISCUSSION: First described by Claudius Amyand (1660-1740), a French born English surgeon, who successfully performed the first reported appendectomy for inflamed appendix encountered during herniotomy on an 11 year-old boy in 1735 at St George's hospital.The incidence of Amyand's hernia is between 1%. The association of appendicitis is even rarer and reported to be around of 0.1%. Losanoff and Basson proposed a classification scheme to determine the surgical management of Amyand's hernia, depending on the status of the appendix KEY WORD: Amyand Hernia, Appendix, Elderly.

Association of subclinical mastitis prevalence with sheep breeds in Greece.

The objective of the research described in this Research Communication was to describe potential associations of subclinical mastitis with sheep breeds in Greece. A countrywide survey (2198 ewes in 111 farms) was performed. Prevalence of subclinical mastitis was 0·260. Results did not indicate any difference in the prevalence of subclinical mastitis between farms with pure-bred and farms with cross-bred animals, nor any difference in prevalence between farms with Greek pure-bred animals and farms with imported pure-bred animals. Results indicated that prevalence of subclinical mastitis was smaller in farms with Assaf-breed (0·100) and higher in farms with Frisarta-breed (0·625) (P < 0·02). Prevalence of mastitis was smaller in farms with Greek traditional indigenous breeds (0·221) (P = 0·007). In a model that included sheep breed and management system in farm, breed emerged as a significant factor for prevalence of subclinical mastitis (P = 0·003).

Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936.

Gene expression is influenced by both genetic variants and the environment. As individuals age, changes in gene expression may be associated with decline in physical and cognitive abilities. We measured transcriptome-wide expression levels in lymphoblastoid cell lines derived from members of the Lothian Birth Cohort 1936 at mean ages 70 and 76 years. Changes in gene expression levels were identified for 1,741 transcripts in 434 individuals. Gene Ontology enrichment analysis indicated an enrichment of biological processes involved in the immune system. Transcriptome-wide association analysis was performed for eleven cognitive, fitness, and biomedical aging-related traits at age 70 years (N=665 to 781) and with mortality. Transcripts for genes (F2RL3, EMILIN1 and CDC42BPA) previously identified as being differentially methylated or expressed in smoking or smoking-related cancers were overexpressed in smokers compared to non-smokers and the expression of transcripts for genes (HERPUD1, GAB2, FAM167A and GLS) previously associated with stress response, autoimmune disease and cancer were associated with telomere length. No associations between expression levels and other traits, or mortality were identified.

A candidate gene approach to study nematode resistance traits in naturally infected sheep.

Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome. A total of twelve single nucleotide polymorphisms (SNPs) were sequenced in IL23R, RORC2 and TBX21 from genomic DNA of Scottish Blackface lambs. Of the twelve SNPs, six were non-synonymous (missense), four were within the 3' UTRs and two were intronic. The association between nine of these SNPs and the traits of body weight, faecal egg count (FEC) and relative T. circumcincta L3-specific IgA antibody levels was assessed in a population of domestic Scottish Blackface ewe lambs and a population of free-living Soay ewe lambs both naturally infected with a mixture of nematodes. There were no significant associations identified between any of the SNPs and phenotypes recorded in either of the populations after adjustment for multiple testing (Bonferroni corrected P value≤0.002). In the Blackface lambs, there was a nominally significant association (P=0.007) between IL23R p.V324M and weight at 20 weeks. This association may be worthy of further investigation in a larger sample of sheep.

Tumor regression grades, K-RAS mutational profile and c-MET in colorectal liver metastases.

INTRODUCTION: Recently TRG, necrosis grade and the rate of viable cancer cells of colorectal liver metastases were correlated with the response to chemotherapy treatments, whereas K-RAS mutations and c-MET over-expression were correlated with the prognosis. METHODS: 58 resection specimens were assessed for regression grades. Patients undergone neo-adjuvant treatments were compared to patients who underwent therapy exclusively adjuvantly. We investigated the K-RAS mutational profile, the c-MET over-expression along with patients' survivals curves. RESULTS: Patients undergone neo-adjuvant treatment presented significant higher fibrosis rates and lower rates of viable cells. 36.7% of the patients had a K-RAS mutation and the 26.7% presented c-MET over-expression, but these features did not correlate with patients' clinical/pathological data. Survival analysis documented that K-RAS WT patients presenting c-MET over-expression had worse outcomes. CONCLUSION: Fibrosis and the rate of viable cells significantly correlate with the response to chemotherapy treatments. c-MET is a promising marker in K-RAS WT patients.

Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle.

BACKGROUND: The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics. METHODS: The present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control. RESULTS: The estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB. CONCLUSION: Genomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.

Genome-wide association reveals QTL for growth, bone and in vivo carcass traits as assessed by computed tomography in Scottish Blackface lambs.

BACKGROUND: Improving meat quality including taste and tenderness is critical to the protection and development of markets for sheep meat. Phenotypic selection for such measures of meat quality is constrained by the fact that these parameters can only be measured post-slaughter. Carcass composition has an impact on meat quality and can be measured on live animals using advanced imaging technologies such as X-ray computed tomography (CT). Since carcass composition traits are heritable, they are potentially amenable to improvement through marker-assisted and genomic selection. We conducted a genome-wide association study (GWAS) on about 600 Scottish Blackface lambs for which detailed carcass composition phenotypes, including bone, fat and muscle components, had been captured using CT and which were genotyped for ~40,000 single nucleotide polymorphisms (SNPs) using the Illumina OvineSNP50 chip. RESULTS: We confirmed that the carcass composition traits were heritable with moderate to high (0.19-0.78) heritabilities. The GWAS analyses revealed multiple SNPs and quantitative trait loci (QTL) that were associated with effects on carcass composition traits and were significant at the genome-wide level. In particular, we identified a region on ovine chromosome 6 (OAR6) associated with bone weight and bone area that harboured SNPs with p values of 5.55 × 10(-8) and 2.63 × 10(-9), respectively. The same region had effects on fat area, fat density, fat weight and muscle density. We identified plausible positional candidate genes for these OAR6 QTL. We also detected a SNP that reached the genome-wide significance threshold with a p value of 7.28 × 10(-7) and was associated with muscle density on OAR1. Using a regional heritability mapping approach, we also detected regions on OAR3 and 24 that reached genome-wide significance for bone density. CONCLUSIONS: We identified QTL on OAR1, 3, 24 and particularly on OAR6 that are associated with effects on muscle, fat and bone traits. Based on available evidence that indicates that these traits are genetically correlated with meat quality traits, these associated SNPs have potential applications in selective breeding for improved meat quality. Further research is required to determine whether the effects associated with the OAR6 QTL are caused by a single gene or several closely-linked genes.