Whole genome scan reveals the genetic signature of African Ankole cattle breed and potential for higher quality beef

BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods. RESULTS: We identified 238 (XP-EHH) and 213 (XP-CLR) positively selected genes, of which 97 were detected from both statistics. Among the genes obtained, we primarily reported those involved in different biological process and pathways associated with meat quality traits. Genes (CAPZB, COL9A2, PDGFRA, MAP3K5, ZNF410, and PKM2) involved in muscle structure and metabolism affect meat tenderness. Genes (PLA2G2A, PARK2, ZNF410, MAP2K3, PLCD3, PLCD1, and ROCK1) related to intramuscular fat (IMF) are involved in adipose metabolism and adipogenesis. MB and SLC48A1 affect meat color. In addition, we identified genes (TIMP2, PKM2, PRKG1, MAP3K5, and ATP8A1) related to feeding efficiency. Among the enriched Gene Ontology Biological Process (GO BP) terms, actin cytoskeleton organization, actin filament-based process, and protein ubiquitination are associated with meat tenderness whereas cellular component organization, negative regulation of actin filament depolymerization and negative regulation of protein complex disassembly are involved in adipocyte regulation. The MAPK pathway is responsible for cell proliferation and plays an important role in hyperplastic growth, which has a positive effect on meat tenderness. CONCLUSION: Results revealed several candidate genes positively selected in Ankole cattle in relation to meat quality characteristics. The genes identified are involved in muscle structure and metabolism, and adipose metabolism and adipogenesis. These genes help in the understanding of the biological mechanisms controlling beef quality characteristics in African Ankole cattle. These results provide a basis for further research on the genomic characteristics of Ankole and other Sanga cattle breeds for quality beef. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-016-0467-1) contains supplementary material, which is available to authorized users

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study

IMPORTANCE Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations.OBJECTIVE To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis.DESIGN, SETTING, AND PARTICIPANTS This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphismswere used as an instrumental variable). Data from 180 056 participants from 49 studies were included.MAIN OUTCOMES AND MEASURES Type 2 diabetes and glycemic traits.RESULTS This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P=4.03 x 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P=.04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P=.04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (beta=0.189; SE=0.060; P=.002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration.CONCLUSIONS AND RELEVANCE In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Lipid traits (total, low-densityand high-density lipoproteincholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related tocardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Atwo-stage epigenome-wide association study was performed, with a discovery sample intheREGICOR study (n=645)and validation in the Framingham Offspring Study (n=2,542).FourteenCpG sites located in 9 genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP andSLC7A11) and 2 intergenic regions showeddifferential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation relatedto total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP andSLC7A11).These CpGs explained0.7%, 9.5% and18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genesSREBF2and SREBF1was inversely associated with methylation of their corresponding CpGs(p-value=0.0042 and 0.0045, respectively) in participants of the GOLDN study(n=98). In turn, SREBF1expression wasdirectly associated with HDL cholesterol(p-value=0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1and CPT1Awerealso associated with lipid profile. Further research is warranted to functionally validatethesenew loci and assess the causality ofnew and established associationsbetween these differentially methylated lociand lipid metabolism.This work was supported by the following sources: Agència de Gestio Ajuts Universitaris de Recerca [2014 SGR 240]; the Spanish Ministry of Economy through the Carlos III Health Institute [ISCIII-FIS-FEDER-ERDF PI12-00232, PI12-01238, PI11-01801, PI08-1327, PI05-1251, PI05-1297, PI02-0471, FIS99/0013-01, FIS96/0026-01, FIS93/0568, FIS92/0009-05], and the Red de Investigacion Cardiovascular [RD12/0042/0013, RD12/0042/0020, RD12/0042/0055, RD12/0042/0061]. S.S-B. was funded by a contract from Instituto de Salud Carlos III FEDER [IFI14/00007] and Daniel Bravo Andreu Private Foundation. GOLDN: The GOLDN study (AND, DA, JO, SA, DKA) was funded by the US National Institute of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih.gov) grants R01HL104135 and U01HL72524