Genome-wide association study revealed putative SNPs and candidate genes associated with growth and meat traits in Japanese quail

The search for SNPs and candidate genes that determine the manifestation of major selected traits is one crucial objective for genomic selection aimed at increasing poultry production efficiency. Here, we report a genome-wide association study (GWAS) for traits characterizing meat performance in the domestic quail. A total of 146 males from an F 2 reference population resulting from crossing a fast (Japanese) and a slow (Texas White) growing breed were examined. Using the genotyping-by-sequencing technique, genomic data were obtained for 115,743 SNPs (92,618 SNPs after quality control) that were employed in this GWAS. The results identified significant SNPs associated with the following traits at 8 weeks of age: body weight (nine SNPs), daily body weight gain (eight SNPs), dressed weight (33 SNPs), and weights of breast (18 SNPs), thigh (eight SNPs), and drumstick (three SNPs). Also, 12 SNPs and five candidate genes (GNAL, DNAJC6, LEPR, SPAG9, and SLC27A4) shared associations with three or more traits. These findings are consistent with the understanding of the genetic complexity of body weight-related traits in quail. The identified SNPs and genes can be used in effective quail breeding as molecular genetic markers for growth and meat characteristics for the purpose of genetic improvement

Genotyping-by-sequencing strategy for integrating genomic structure, diversity and performance of various Japanese quail (Coturnix japonica) breeds

Simple Summary: Artificial selection has been applied to domesticated birds for many decades. More recently, this selection has made use of so-called single-nucleotide polymorphism (SNP) markers—simple variants in a DNA sequence. These SNPs can be used for whole-genome screening to detect the unique traces of areas of the genome that are subject to selection. Doing this may help to shed light on the evolutionary and family history (phylogeny) of domestic Japanese quails of different breeds and utility types (e.g., egg, meat or dual-purpose breeds). In this study, 99 birds were used, representing eight breeds (11% of the world’s quail gene pool) and various purposes of use to gather genetic (whole-genome) data in the first-ever analysis of its kind performed on domestic quails. We thereby uncovered evolutionary relationships and points of divergence of individual quail breeds, gleaning important insights into the genetic diversity of domestic quail breeds and their future breeding potential. Abstract: Traces of long-term artificial selection can be detected in genomes of domesticated birds via whole-genome screening using single-nucleotide polymorphism (SNP) markers. This study thus examined putative genomic regions under selection that are relevant to the development history, divergence and phylogeny among Japanese quails of various breeds and utility types. We sampled 99 birds from eight breeds (11% of the global gene pool) of egg (Japanese, English White, English Black, Tuxedo and Manchurian Golden), meat (Texas White and Pharaoh) and dual-purpose (Estonian) types. The genotyping-by-sequencing analysis was performed for the first time in domestic quails, providing 62,935 SNPs. Using principal component analysis, Neighbor-Net and Admixture algorithms, the studied breeds were characterized according to their genomic architecture, ancestry and direction of selective breeding. Japanese and Pharaoh breeds had the smallest number and length of homozygous segments indicating a lower selective pressure. Tuxedo and Texas White breeds showed the highest values of these indicators and genomic inbreeding suggesting a greater homozygosity. We revealed evidence for the integration of genomic and performance data, and our findings are applicable for elucidating the history of creation and genomic variability in quail breeds that, in turn, will be useful for future breeding improvement strategies

Survival in amoeba: a major selection pressure on the presence of bacterial copper and zinc resistance determinants?: identification of a "copper pathogenicity island"

The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Identification of SNPs and candidate genes associated with abdominal fat deposition in quails (Coturnix japonica) [Идентификация SNPs и генов-кандидатов, ассоциированных с отложением абдоминального жира у перепелов Coturnix japonica]

The rate of fat deposition, including abdominal fat, is one of the important indicators characterizing both meat performance and product quality, as well as the poultry welfare in general. This trait positively correlates with the bird’s rapid growth and largely depends not only on feeding and housing conditions, but also on genetic factors. Mostly, data on the genetic mechanisms that determine fat metabolism and fat deposition rate have been obtained in chickens; SNPs and candidate genes that determine the deposition of both intramuscular and abdominal fat have been identified. The number of similar studies on quail is relatively small. To date, there is not enough information in the specialized literature about quantitative trait loci (QTLs) that are reliably associated with fat metabolism indices in quails. The present work reports for the first time the identified SNPs that are highly significantly (p < 0.00001) associated with the intensity of abdominal fat deposition in 8-week-old quails from the F2 model resource population. In the region of identified SNPs, candidate genes reliably associated with this trait were established. The objective of the study was to search for SNPs and identify candidate genes associated with abdominal fat deposition in quails. The studies were carried out on F2 males of the model resource population (n = 146) obtained by crossing two quail breeds contrasting in growth rate and meat quality, Japanese (slow growth) and Texas (fast growth). F2 individuals were genotyped using the GBS (genotyping-by-sequencing) method. To identify associations between genome-wide genotyping data and the amount of abdominal fat, PLINK 1.9 software was used with accepted filter settings (geno 0.1, mind 0.1, maf 0.05). The threshold significance criterion was set to p < 0.00001. The resultant F2 resource population of quail was characterized by high variability in the content of abdominal fat in the carcass. At the age of 56 days, this indicator varied from 0.01 to 10.46 g and averaged 2.41±0.16 g. Based on the GWAS (genome-wide association study) analysis, we identified 29 SNPs and 11 candidate genes located in the regions of these SNPs that were associated with abdominal fat deposition in quail. The determined SNPs are localized on chromosomes 1, 2, 7, 8, 17, 19, 21, 24 and 28. The candidate genes identified (CNTN5, GNAL, PDE1A, RBMS1, PTPRF, SH3GLB2, SLC27A4, TRIM62, IGSF9B, USHBP1, and NR2F6) were established on chromosomes CJA1 (1 gene), CJA2 (1 gene), CJA7 (2 genes), CJA8 (1 gene), CJA17 (2 genes), CJA21 (1 gene), CJA24 (1 gene) and CJA28 (2 genes). The detected SNPs and candidate genes can serve as genetic markers in breeding programs to improve the meat quality of quails and reduce the fat content in carcasses. Волкова, Н.А., Герман, Н.Ю., Ларионова, П.В., Ветох, А.Н., Романов М.Н., & Зиновьева, Н.А. Интенсивность отложения жира, в том числе абдоминального, — один из важных показателей, характеризующих как мясную продуктивность и качество продукции, так и общее здоровье сельскохозяйственной птицы. Этот признак положительно коррелирует с быстрым ростом птицы и в значительной степени зависит не только от условий кормления и содержания, но и от генетических факторов. В основном данные о генетических механизмах, обусловливающих жировой обмен и интенсивность отложения жира, получены на курах, идентифицированы SNPs и геныкандидаты, детерминирующие отложение как внутримышечного, так и брюшного (абдоминального) жира. Число подобных исследований на перепелах относительно невелико. К настоящему времени в специальной литературе недостаточно информации о локусах количественных признаков (QTL), достоверно связанных с показателями жирового обмена у перепелов. В представленной работе впервые сообщается о выявленных SNPs, с высокой достоверностью (p < 0,00001) ассоциированных с интенсивностью отложения абдоминального жира у 8-недельных перепелов из F2 модельной ресурсной популяции. В области выявленных SNPs установлены гены-кандидаты, достоверно связанные с этим признаком. Целью работы были поиск SNPs и идентификация генов-кандидатов, связанных с отложением абдоминального жира у перепелов. Исследования проводили на самцах F2 модельной ресурсной популяции (n = 146), полученной при скрещивании двух контрастных по скорости роста и мясным качествам пород — японских (медленный рост) и техасских (быстрый рост) перепелов. Особей F2 генотипировали методом GBS (genotyping-by-sequencing, генотипирование посредством секвенирования). Для выявления ассоциаций между данными полногеномного генотипирования и количеством абдоминального жира использовали программное обеспечение PLINK 1.9 с принятыми ограничениями (geno 0,1; mind 0,1; maf 0,05). В качестве порогового критерия достоверности установили p < 0,00001. Полученная F2 ресурсная популяция перепелов характеризовалась высокой вариабельностью по содержанию абдоминального жира в туше. В возрасте 56 сут этот показатель варьировал от 0,01 до 10,46 г и составил в среднем 2,41±0,16 г. На основании проведенного GWAS-анализа (genome-wide association study) идентифицировали 29 SNPs и 11 генов-кандидатов, находящихся в областях расположения этих SNPs, которые ассоциированы с отложением абдоминального жира у перепелов. Обнаруженные SNPs локализуются на хромосомах 1, 2, 7, 8, 17, 19, 21, 24 и 28. Установленные гены-кандидаты (CNTN5, GNAL, PDE1A, RBMS1, PTPRF, SH3GLB2, SLC27A4, TRIM62, IGSF9B, USHBP1, NR2F6) идентифицированы на хромосомах CJA1 (1), CJA2 (1), CJA7 (2), CJA8 (1), CJA17 (2), CJA21 (1), CJA24 (1) и CJA28 (2). Детектированные SNP и гены-кандидаты могут послужить генетическими маркерами в программах селекции на улучшение мясных качеств перепелов и снижение содержания жира в тушках

Genome-Wide Association Study Revealed Putative SNPs and Candidate Genes Associated with Growth and Meat Traits in Japanese Quail

The search for SNPs and candidate genes that determine the manifestation of major selected traits is one crucial objective for genomic selection aimed at increasing poultry production efficiency. Here, we report a genome-wide association study (GWAS) for traits characterizing meat performance in the domestic quail. A total of 146 males from an F2 reference population resulting from crossing a fast (Japanese) and a slow (Texas White) growing breed were examined. Using the genotyping-by-sequencing technique, genomic data were obtained for 115,743 SNPs (92,618 SNPs after quality control) that were employed in this GWAS. The results identified significant SNPs associated with the following traits at 8 weeks of age: body weight (nine SNPs), daily body weight gain (eight SNPs), dressed weight (33 SNPs), and weights of breast (18 SNPs), thigh (eight SNPs), and drumstick (three SNPs). Also, 12 SNPs and five candidate genes (GNAL, DNAJC6, LEPR, SPAG9, and SLC27A4) shared associations with three or more traits. These findings are consistent with the understanding of the genetic complexity of body weight-related traits in quail. The identified SNPs and genes can be used in effective quail breeding as molecular genetic markers for growth and meat characteristics for the purpose of genetic improvement

Genotyping-by-Sequencing Strategy for Integrating Genomic Structure, Diversity and Performance of Various Japanese Quail (Coturnix japonica) Breeds

Traces of long-term artificial selection can be detected in genomes of domesticated birds via whole-genome screening using single-nucleotide polymorphism (SNP) markers. This study thus examined putative genomic regions under selection that are relevant to the development history, divergence and phylogeny among Japanese quails of various breeds and utility types. We sampled 99 birds from eight breeds (11% of the global gene pool) of egg (Japanese, English White, English Black, Tuxedo and Manchurian Golden), meat (Texas White and Pharaoh) and dual-purpose (Estonian) types. The genotyping-by-sequencing analysis was performed for the first time in domestic quails, providing 62,935 SNPs. Using principal component analysis, Neighbor-Net and Admixture algorithms, the studied breeds were characterized according to their genomic architecture, ancestry and direction of selective breeding. Japanese and Pharaoh breeds had the smallest number and length of homozygous segments indicating a lower selective pressure. Tuxedo and Texas White breeds showed the highest values of these indicators and genomic inbreeding suggesting a greater homozygosity. We revealed evidence for the integration of genomic and performance data, and our findings are applicable for elucidating the history of creation and genomic variability in quail breeds that, in turn, will be useful for future breeding improvement strategies