Comparative Transcriptome Analysis of Milk Somatic Cells During Lactation Between Two Intensively Reared Dairy Sheep Breeds

In dairy sheep industry, milk production dictates the value of a ewe. Milk production is directly related to the morphology and physiology of the mammary gland; both being designated targets of breeding strategies. Although within a flock breeding parameters are mutual, large differences in milk production among individual ewes are usually observed. In this work, we tested two of the most productive dairy sheep breeds reared intensively in Greece, one local the Chios breed and one foreign the Lacaune breed. We used transcriptome sequencing to reveal molecular mechanisms that render the mammary gland highly productive or not. While highly expressed genes (caseins and major whey protein genes) were common among breeds, differences were observed in differentially expressed genes. ENSOARG00000008077, as a member of ribosomal protein 14 family, together with LPCAT2, CCR3, GPSM2, ZNF131, and ASIP were among the genes significantly differentiating mammary gland’s productivity in high yielding ewes. Gene ontology terms were mainly linked to the inherent transcriptional activity of the mammary gland (GO:0005524, GO:0030552, GO:0016740, GO:0004842), lipid transfer activity (GO:0005319) and innate immunity (GO:0002376, GO:0075528, GO:0002520). In addition, clusters of genes affecting zinc and iron trafficking into mitochondria were highlighted for high yielding ewes (GO:0071294, GO:0010043). Our analyses provide insights into the molecular pathways involved in lactation between ewes of different performances. Results revealed management issues that should be addressed by breeders in order to move toward increased milk yields through selection of the desired phenotypes. Our results will also contribute toward the selection of the most resilient and productive ewes, thus, will strengthen the existing breeding systems against a spectrum of environmental threats

A genome-wide association study reveals novel SNP markers associated with resilience traits in two Mediterranean dairy sheep breeds

Genetic selection for higher productivity increased dairy sheep susceptibility to diseases and environmental stressors, challenging their health and welfare status and production efficiency. Improving resilience to such stressors can enhance their ability to face these challenges without compromising productivity. Our objective was to estimate genomic heritability and perform genome-wide association studies (GWAS) to detect SNPs and candidate genes associated with three proxy traits for resilience (milk somatic cell count—SCC, lactation persistency—LP, body condition score—BCS) of Chios and Frizarta dairy ewes. We used genome-wide genotypes of 317 Chios and 346 Frizarta ewes. Individual records of milk yield and BCS, and milk samples were collected monthly for two consecutive milking periods; samples were analyzed to determine SCC. The LP was calculated as the regression coefficient of daily milk yield on days from lambing. Within breed, variance components analyses and GWAS were performed using genomic relatedness matrices in single-trait animal linear mixed models. Genomic-based heritability estimates were relatively high (BCS: h2 = 0.54 and 0.55, SCC: h2 = 0.25 and 0.38, LP: h2 = 0.43 and 0.45, for Chios and Frizarta ewes, respectively), compared to previous pedigree-based studies. The GWAS revealed 7 novel SNPs associated with the studied traits; one genome-wide and two suggestive significant SNPs for SCC (Frizarta: rs403061409, rs424064526 and rs428540973, on chromosomes 9, 1 and 12, respectively), one suggestive significant SNP for BCS (Chios: rs424834097 on chromosome 4) and three suggestive significant SNPs for LP (Frizarta: rs193632931 and rs412648955 on chromosomes 1 and 6, Chios: rs428128299 on chromosome 3). Nineteen candidate genes were detected: two for BCS (Chios: POT1, TMEM229A), thirteen for SCC (Frizarta: NTAQ1, ZHX1, ZHX2, LOC101109545, HAS2, DERL1, FAM83A, ATAD2, RBP7, FSTL1, CD80, HCLS1, GSK3B) and four for LP (Frizarta: GRID2, FAIM, CEP70—Chios: GRIP1). Present results show that resilience in the studied dairy sheep breeds is heritable and advance existing knowledge on the genomic background of SCC, LP, and BCS. Future research will quantify effects of different alleles of significant SNPs on the studied traits and search for possible correlations among traits to facilitate their effective incorporation in breeding programs aiming to improve resilience

A genome-wide association study reveals novel SNP markers associated with resilience traits in two Mediterranean dairy sheep breeds

Genetic selection for higher productivity increased dairy sheep susceptibility to diseases and environmental stressors, challenging their health and welfare status and production efficiency. Improving resilience to such stressors can enhance their ability to face these challenges without compromising productivity. Our objective was to estimate genomic heritability and perform genome-wide association studies (GWAS) to detect SNPs and candidate genes associated with three proxy traits for resilience (milk somatic cell count—SCC, lactation persistency—LP, body condition score—BCS) of Chios and Frizarta dairy ewes. We used genome-wide genotypes of 317 Chios and 346 Frizarta ewes. Individual records of milk yield and BCS, and milk samples were collected monthly for two consecutive milking periods; samples were analyzed to determine SCC. The LP was calculated as the regression coefficient of daily milk yield on days from lambing. Within breed, variance components analyses and GWAS were performed using genomic relatedness matrices in single-trait animal linear mixed models. Genomic-based heritability estimates were relatively high (BCS: h2 = 0.54 and 0.55, SCC: h2 = 0.25 and 0.38, LP: h2 = 0.43 and 0.45, for Chios and Frizarta ewes, respectively), compared to previous pedigree-based studies. The GWAS revealed 7 novel SNPs associated with the studied traits; one genome-wide and two suggestive significant SNPs for SCC (Frizarta: rs403061409, rs424064526 and rs428540973, on chromosomes 9, 1 and 12, respectively), one suggestive significant SNP for BCS (Chios: rs424834097 on chromosome 4) and three suggestive significant SNPs for LP (Frizarta: rs193632931 and rs412648955 on chromosomes 1 and 6, Chios: rs428128299 on chromosome 3). Nineteen candidate genes were detected: two for BCS (Chios: POT1, TMEM229A), thirteen for SCC (Frizarta: NTAQ1, ZHX1, ZHX2, LOC101109545, HAS2, DERL1, FAM83A, ATAD2, RBP7, FSTL1, CD80, HCLS1, GSK3B) and four for LP (Frizarta: GRID2, FAIM, CEP70—Chios: GRIP1). Present results show that resilience in the studied dairy sheep breeds is heritable and advance existing knowledge on the genomic background of SCC, LP, and BCS. Future research will quantify effects of different alleles of significant SNPs on the studied traits and search for possible correlations among traits to facilitate their effective incorporation in breeding programs aiming to improve resilience.</p

The transmittable through stinging microbiota differs between honeybees and wasps: a potentially greater microbial risk of the wasp sting for humans

The present research investigated whether accidental contact through stinging with honeybees, wasps, and hornets could represent a microbial hazard for humans. It has been previously suggested that such contact may transmit pathogens causing infections that could even be fatal for some susceptible individuals. Stinging simulation experiments were performed in the lab with live insects collected from the environment in Lemnos Island (north-eastern Greece), while different selective agar media targeting some clinically important bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis/faecium, and Pseudomonas aeruginosa) were used as substrates for microbial recovery and identification. Results revealed none of the target pathogenic bacterial species in the honeybee samples, with bacilli, staphylococci, and micrococci dominating their surveyed microbiota. However, most of the suspect colonies isolated from wasps and hornets belonged to important hygienic indicators (i.e., enterococci, Proteus mirabilis, and coliforms), implying possible contact of these insects with fecal origin materials. To sum up, the microbiota that may be transmitted to humans through stinging appears to differ between honeybees and wasps/hornets, while the isolation from the latter samples of some other important opportunistic pathogens, such as Enterobacter spp. and Klebsiella spp., also known for multidrug resistance, could be an additional reason of concern

Diet supplementation with fish‐derived extracts suppresses diabetes and modulates intestinal microbiome in a murine model of diet‐induced obesity

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.publishedVersio

Diet supplementation with fish‐derived extracts suppresses diabetes and modulates intestinal microbiome in a murine model of diet‐induced obesity

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.publishedVersio

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on similar to 4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.Peer reviewe

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations