Expression of Beef- Versus Dairy-Type in Crossbred Beef × Dairy Cattle Does Not Impact Shape, Eating Quality, or Color of Strip Loin Steaks

Phenotypic expression of dairy influence often carries negative implications in beef production; thus, considerable variation in expression of beef- versus dairy-type might adversely affect value of crossbred beef × dairy cattle. This study evaluated effects of phenotype in crossbred beef × dairy cattle, specifically that associated with beef- versus dairy-type, on meat quality. Effects were blocked within commercial feedlot pens because cattle within a pen were contemporaries for sex, age, management, and source. On their harvest date, 592 Angus or [Simmental × Angus] × Holstein cattle from 9 pens were assessed by 3 expert evaluators. Scores for muscling and frame size were used to categorize and subset cattle in a pen into 4 phenotype groups: (1) fully dairy-type, (2) partially dairy-type, (3) partially beef-type, and (4) fully beef-type. Strip loin steaks were obtained from selected cattle (n = 82 to 84 per group) and evaluated for descriptive sensory attributes, shear force, pH, color at retail display, steak dimensions, muscle fiber type, and fatty acid composition. Data were tested for fixed effects of phenotype group with random effects of pen. Despite distinct expression of visual beef- versus dairy-type among cattle sampled, phenotype groups were largely not different (P > 0.05) in shape, sensory attributes, color, or biochemical properties of strip loin steaks. Other body regions, separate from the loin, were likely responsible for differences in live animal muscling. Additional research is needed on effects of sire breed, individual sire, and management strategies on meat quality in beef × dairy crossbreds. Complementarity of beef breeds and sires to produce more profitable beef-type cattle from the beef × dairy mating system should not be expected to negatively influence meat quality. Marketing programs rooted in production of consistent and premium products may benefit from including beef from beef × dairy crossbreds

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Influence of Megasphaera elsdenii and feeding strategies on feedlot performance, compositional growth, and carcass parameters of early weaned, beef calves

© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]–Angus calves [n = 135; 72 steers and 63 heifers; body weight (BW) = 212.4 kg ± 36.1] were early weaned (~5 mo) to evaluate multiple feeding regimens (conventional vs. aggressive energy diets ± Megasphaera elsdenii NCIMB 41125 (M. elsdenii culture (MEC); Lactipro Advance; MS Biotec Inc., Wamego, KS) in order to elucidate the optimal development strategy. Objectives were measured by tracking the effects of caloric density and oral drenching of growing phase performance and subsequent carcass traits. The 72-d experiment featured three groups: 1) control (CON), fed exclusively a 35% roughage diet; 2) aggressive (AGR), fed a blend of a 10% and 35% roughage diets; 3) MEC, fed the same diet as AGR and drenched with 50 mL of M. elsdenii NCIMB 41125 on day 1. A subset of calves (n = 45) was equipped with wireless rumination tags (Allflex Flex Tag; SCR Engineers, Ltd; Netanya, Israel), which logged daily rumination and general activity. Skeletal growth variables were assessed by measuring wither and hip height pretrial and posttrial. Ultrasonography provided additional resolution concerning growing phase compositional gain, which was later verified by carcass data collection. Data were analyzed as a nested analysis of variance with BW and gender serving as blocking factors. The increased caloric density of the diets administered to MEC and AGR calves resulted in greater average daily gain and gain:feed values compared with CON even during the first 21 d of diet acclimation (P ≤ 0.05). Additional fiber concentration of CON diets led to increased rumination times in 9 of the 10 wk of trial (P ≤ 0.10). No differences amongst treatments were detected for skeletal variables or ultrasound 12th rib fat. Cattle fed CON diets posted 3.4% inferior BW at the end of the growing period trial and a 3.8% reduction in hot carcass weight (HCW), reinforcing the theory that intensifying caloric intake during the growing phase does not compromise future feedlot performance. Ultrasound marbling scores for MEC-treated cattle were 19° greater than AGR treated cattle (P ≤ 0.05) at the end of the growing phase trial. Nearly the exact same advantage (22°) was observed in the cooler 5 mo later (P = 0.42). Implying MEC metabolically imprinted cattle to favor marbling development. It appears that maximizing dietary caloric density in light-weight calves does not adversely affect the growth curve, while oral dosing of MEC during the growing period may be a precursor for enhanced quality grade