An assessment of the production, reproduction, and functional traits of Holstein-Friesian, Jersey × Holstein-Friesian, and Norwegian Red × (Jersey × Holstein-Friesian) cows in pasture-based systems

Peer-ReviewedPasture-based production systems typically require highly fertile, healthy, and robust genetics, with greater emphasis on milk solids (MSo; kg of fat + protein) production as opposed to milk yield. This study assessed milk production, production efficiency, reproductive performance, body weight (BW), body condition score, and functional traits in 3 different dairy cow genotypes: Holstein-Friesian (HF), Jersey × Holstein-Friesian (JEX), and Norwegian Red × (Jersey × Holstein- Friesian) (3-way). The 3 genotypes were rotationally grazed on 4 different grazing treatments after calving in spring and were stocked at a rate of 2.75 cows/ha. Holstein-Friesian cows produced higher daily and total milk yields compared with JEX and 3-way cows (5,718 vs. 5,476 and 5,365 kg/cow, respectively). However, JEX and 3-way cows had higher milk fat and protein contents (4.86 and 4.75%, respectively, for JEX and 3.87 and 3.88%, respectively, for 3-way) compared with HF (4.52 and 3.72%), resulting in similar MSo yield for JEX and HF (469 and 460 kg/cow) and slightly lower MSo yield for 3-way (453 kg/cow) compared with JEX. As parity increased, milk and MSo yield per cow increased. Reproductive performance was not significantly different between the 3 genotypes, which had similar 24-d submission rates, 6-wk pregnancy rates, and overall pregnancy rates over the 4-yr period. No difference in calving difficulty, incidence of mastitis, or incidence of lameness was observed among the 3 genotypes. Body weight was significantly different among all 3 genotypes, with HF being the heaviest followed by 3-way and JEX (530, 499, and 478 kg, respectively), and 3-way cows had a higher body condition score throughout lactation compared with HF and JEX cows. The differences in BW coupled with similar MSo production resulted in JEX cows having the highest production efficiency (4.58 kg of MSo/kg of metabolic BW), 3-way cows being intermediate (4.30 kg of MSo/kg of metabolic BW), and HF cows having the lowest (4.16 kg of MSo/kg of metabolic BW). In conclusion, HF herds with poor reproductive performance and low milk fat and protein contents are likely to benefit considerably from crossbreeding with Jersey, and all herds are likely to benefit in terms of production efficiency. However, where herd performance, particularly in relation to reproductive performance, is comparable with HF in the current study, crossbreeding with Jersey or Norwegian Red is unlikely to lead to significant improvements in overall herd performance

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Prostate-specific antigen testing accuracy in community practice

BACKGROUND: Most data on prostate-specific antigen (PSA) testing come from urologic cohorts comprised of volunteers for screening programs. We evaluated the diagnostic accuracy of PSA testing for detecting prostate cancer in community practice. METHODS: PSA testing results were compared with a reference standard of prostate biopsy. Subjects were 2,620 men 40 years and older undergoing (PSA) testing and biopsy from 1/1/95 through 12/31/98 in the Albuquerque, New Mexico metropolitan area. Diagnostic measures included the area under the receiver-operating characteristic curve, sensitivity, specificity, and likelihood ratios. RESULTS: Cancer was detected in 930 subjects (35%). The area under the ROC curve was 0.67 and the PSA cutpoint of 4 ng/ml had a sensitivity of 86% and a specificity of 33%. The likelihood ratio for a positive test (LR+) was 1.28 and 0.42 for a negative test (LR-). PSA testing was most sensitive (90%) but least specific (27%) in older men. Age-specific reference ranges improved specificity in older men (49%) but decreased sensitivity (70%), with an LR+ of 1.38. Lowering the PSA cutpoint to 2 ng/ml resulted in a sensitivity of 95%, a specificity of 20%, and an LR+ of 1.19. CONCLUSIONS: PSA testing had fair discriminating power for detecting prostate cancer in community practice. The PSA cutpoint of 4 ng/ml was sensitive but relatively non-specific and associated likelihood ratios only moderately revised probabilities for cancer. Using age-specific reference ranges and a PSA cutpoint below 4 ng/ml improved test specificity and sensitivity, respectively, but did not improve the overall accuracy of PSA testing

Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing

The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, ‘bifidobacteria-optimised’ universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria

Absence of Adolescent Obesity in Grenada: Is This a Generational Effect?

Background: Low- and middle-income countries are affected disproportionately by the ongoing global obesity pandemic. Representing a middle income country, the high prevalence of obesity among Grenadian adults as compared to US adults is expected as part of global obesity trends. The objective of this study was to determine if Grenadian adolescents have a higher prevalence of overweight compared to their US counterparts, and if a disparity exists between urban and rural adolescents.Methods: Using a subcohort of participants in the Grenadian Nutrition Student Survey, diet quality and anthropometric measures were collected from 55% of the classrooms of first year secondary students in Grenada (n = 639). Rural or urban designations were given to each school. Body Mass Index (BMI) was calculated and categorized as overweight or obese for each student following CDC classification cutoffs. A standardized BMI (BMIz) was calculated for each school. Sex-specific BMI and overall BMIz were compared to a 1980s US cohort. Multilevel models, overall and stratified by sex, of students nested within schools were conducted to determine if BMIz differed by rural or urban locality, gender, and diet quality.Results: The mean age of this cohort was 12.7 (SD = 0.8) years with 83.8% of the cohort identifying as Afro-Caribbean. Females had nearly twice the prevalence of overweight when compared to males (22.7 vs. 12.2%) but a similar prevalence of obesity (8.2 vs. 6.8%). Grenadian adolescents had lower prevalence of overweight (females: 22.7 vs. 44.7%; males: 12.2 vs. 38.8%, respectively) as compared to US counterparts. Eating a traditional diet was negatively associated with BMIz score among females (β^ = −0.395; SE = 0.123) in a stratified, multilevel analysis. BMIz scores did not differ significantly by rural or urban school designation.Conclusions: Among Grenadian adolescents, this study identified a lower overweight prevalence compared to US counterparts and no difference in overweight prevalence by urban or rural location. We hypothesize that the late introduction of processed foods to Grenada protected this cohort from obesogenic promoters due to a lack of fetal overnutrition. However, further research in subsequent birth cohorts is needed to determine if adolescent obesity will increase due to a generational effect

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences

A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Background: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective: We evaluated 6,706 cis-acting expression-associated variants (eSNP) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods: eSNP were tested for association with asthma in 359 asthma cases and 846 controls from the Childhood Asthma Management Program, with verification using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE)-qPCR and Chromatin-Immunoprecipitation (ChIP)-PCR in lung derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results: Cis-acting eSNP demonstrated associations with asthma in both cohorts. We confirmed the previously-reported association of ORMDL3/GSDMB variants with asthma (combined p=2.9 × 108). Reproducible associations were also observed for eSNP in three additional genes: FADS2 (p=0.002), NAGA (p=0.0002), and F13A1 (p=0.0001). We subsequently demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatics, and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes, and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes