The relationship between anogenital distance and fertility, and genome-wide associations for anogenital distance in Irish Holstein-Friesian cows

peer-reviewedThe evaluation of anogenital distance (AGD), the distance from the center of the anus to base of the clitoris, as a potential fertility trait for genetic selection in dairy cows has generated recent interest. The objectives of this cross-sectional observational study were to (1) characterize the distribution and variability of AGD, (2) determine factors associated with AGD, (3) estimate heritability for AGD, (4) identify single nucleotide polymorphisms (SNP) associated with phenotypic variation of AGD, and (5) validate the relationship between categories of AGD and fertility in Irish Holstein-Friesian cows. Anogenital distance was measured using digital calipers in 1,180 Holstein cows (mean ± standard deviation: 225 ± 79 d in milk) from 10 dairy herds located in Munster, Ireland. In addition, age (yr), weight (kg), height at hip (cm), and body condition score (BCS) at the time of AGD measurement were determined in a subset of 281 cows. Genotype information available from 908 cows was subsequently imputed to the Illumina Bovine High Density BeadChip (Illumina Inc., San Diego, CA) for genome-wide association analysis of phenotypic variation in AGD. Overall, AGD had a normal distribution and high variability (mean ± standard deviation; 119.2 ± 11.6 mm). Anogenital distance was weakly but positively associated with cow age, hip height, and body weight, and negatively associated with BCS; the phenotypic variation in AGD that was explainable by these variables was small (coefficient of determination; R2 = 0.09, 0.06, 0.10, and 0.02, respectively). The estimated heritability for AGD was 0.37 (standard error of mean ± 0.08). Six SNP of suggestive significance were identified on Bos taurus autosomes 6, 15, 20, and 26; however, none of these SNP was related to previously identified candidate genes for fertility. Cows were categorized into quartiles (Q1; 86 to 111 mm; n = 311, Q2; 112 to 120 mm; n = 330; Q3; 121 to 127 mm; n = 265, and Q4; 128 to 160 mm; n = 274) based on AGD and the association with reproductive outcomes examined (21-d submission rate, pregnancy to first AI, pregnancy rate within 21, 42 and 84-d after the farm mating start date, and number of times bred). None of the reproductive variables differed significantly between AGD categories. In summary, despite identification of high variability and moderate heritability for AGD in Irish Holstein-Friesian cows, reproductive outcomes did not differ between categories of AGD. This latter result differs from our previous finding of an inverse relationship between AGD and pregnancy outcomes in first- and second-parity Canadian Holstein cows, emphasizing the need to test and validate this new phenotype in diverse cow populations

Mutations Associated with Sulfadoxine-Pyrimethamine and Chlorproguanil Resistance in Plasmodium falciparum Isolates from Blantyre, Malawi

We conducted a prevalence study of mutations in Plasmodium falciparum that are associated with antifolate resistance in Blantyre, Malawi. The dihydrofolate reductase 164-Leu mutation, which confers resistance to both pyrimethamine and chlorproguanil, was found in 4.7% of the samples. Previously unreported mutations in dihydropteroate synthase were also found

Ethiopian indigenous goats offer insights into past and recent demographic dynamics and localadaptation in sub-Saharan African goats

Abstract Knowledge on how adaptive evolution and human socio‐cultural and economic interests shaped livestock genomes particularly in sub‐Saharan Africa remains limited. Ethiopia is in a geographic region that has been critical in the history of African agriculture with ancient and diverse human ethnicity and bio‐climatic conditions. Using 52K genome‐wide data analysed in 646 individuals from 13 Ethiopian indigenous goat populations, we observed high levels of genetic variation. Although runs of homozygosity (ROH) were ubiquitous genome‐wide, there were clear differences in patterns of ROH length and abundance and in effective population sizes illustrating differences in genome homozygosity, evolutionary history, and management. Phylogenetic analysis incorporating patterns of genetic differentiation and gene flow with ancestry modelling highlighted past and recent intermixing and possible two deep ancient genetic ancestries that could have been brought by humans with the first introduction of goats in Africa. We observed four strong selection signatures that were specific to Arsi‐Bale and Nubian goats. These signatures overlapped genomic regions with genes associated with morphological, adaptation, reproduction and production traits due possibly to selection under environmental constraints and/or human preferences. The regions also overlapped uncharacterized genes, calling for a comprehensive annotation of the goat genome. Our results provide insights into mechanisms leading to genome variation and differentiation in sub‐Saharan Africa indigenous goats

Development of a TaqMan Allelic Discrimination Assay for detection of Single Nucleotides Polymorphisms associated with anti-malarial drug resistance

<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance poses a threat to current global efforts towards control and elimination of malaria. Several methods are used in monitoring anti-malarial drug resistance. Molecular markers such as single nucleotide polymorphism (SNP) for example are increasingly being used to identify genetic mutations related to anti-malarial drug resistance. Several methods are currently being used in analysis of SNP associated with anti-malarial drug resistance and although each one of these methods has unique strengths and shortcoming, there is still need to improve and/or develop new methods that will close the gap found in the current methods.</p> <p>Methods</p> <p>TaqMan Allelic Discrimination assays for detection of SNPs associated with anti-malarial drug resistance were designed for analysis on Applied Biosystems PCR platform. These assays were designed by submitting SNP sequences associated with anti-malarial drug resistance to Applied Biosystems website. Eleven SNPs associated with resistance to anti-malarial drugs were selected and tested. The performance of each SNP assay was tested by creating plasmid DNAs carrying codons of interests and analysing them for analysis. To test the sensitivity and specificity of each SNP assay, 12 clinical samples were sequenced at codons of interest and used in the analysis. Plasmid DNAs were used to establish the Limit of Detection (LoD) for each assay.</p> <p>Results</p> <p>Data from genetic profiles of the <it>Plasmodium falciparum </it>laboratory strains and sequence data from 12 clinical samples was used as the reference method with which the performance of the SNP assays were compared to. The sensitivity and specificity of each SNP assay was establish at 100%. LoD for each assay was established at 2 GE, equivalent to less than 1 parasite/μL. SNP assays performed well in detecting mixed infection and analysis of clinical samples.</p> <p>Conclusion</p> <p>TaqMan Allelic Discrimination assay provides a good alternative tool in detection of SNPs associated with anti-malarial drug.</p

World Antimalarial Resistance Network (WARN) II: In vitro antimalarial drug susceptibility

Intrinsic resistance of Plasmodium falciparum is clearly a major determinant of the clinical failure of antimalarial drugs. However, complex interactions between the host, the parasite and the drug obscure the ability to define parasite drug resistance in vivo. The in vitro antimalarial drug susceptibility assay determines ex-vivo growth of parasite in the presence of serial drug concentrations and, thus, eliminates host effects, such as drug metabolism and immunity. Although the sensitivity of the parasite to various antimalarials provided by such a test provides an important indicator of intrinsic parasite susceptibility, there are fundamental methodological issues that undermine comparison of in vitro susceptibility both between laboratories and within a single laboratory over time. A network of laboratories is proposed that will agree on the basic parameters of the in vitro test and associated measures of quality control. The aim of the network would be to establish baseline values of sensitivity to commonly used antimalarial agents from key regions of the world, and create a global database, linked to clinical, molecular and pharmacology databases, to support active surveillance to monitor temporal trends in parasite susceptibility. Such a network would facilitate the rapid detection of strains with novel antimalarial resistance profiles and investigate suitable alternative treatments with retained efficacy

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

peer-reviewedH.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B). H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato acknowledges the European Union (EU) Collaborative Project LowInputBreeds (grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge the German Holstein Association (DHV) and the Confederación de Asociaciones de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576). M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the Holstein genotypes. P.S. acknowledges funding from the Genome Canada project entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing computing resources. J.F.T. was supported by the National Institute of Food and Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and 2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011- 001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V. acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and New Zealand Holstein and Jersey bulls.Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals

Analysis of genome-wide DNA arrays reveals the genomic population structure and diversity in autochthonous Greek goat breeds

Goats play an important role in the livestock sector in Greece. The national herd consists mainly of two indigenous breeds, the Eghoria and Skopelos. Here, we report the population structure and genomic profiles of these two native goat breeds using Illumina's Goat SNP50 BeadChip. Moreover, we present a panel of candidate markers acquired using different genetic models for breed discrimination. Quality control on the initial dataset resulted in 48,841 SNPs kept for downstream analysis. Principal component and admixture analyses were applied to assess population structure. The rate of inbreeding within breed was evaluated based on the distribution of runs of homozygosity in the genome and respective coefficients, the genomic relationship matrix, the patterns of linkage disequilibrium, and the historic effective population size. Results showed that both breeds exhibit high levels of genetic diversity. Level of inbreeding between the two breeds estimated by the Wright's fixation index FST was low (Fst = 0.04362), indicating the existence of a weak genetic differentiation between them. In addition, grouping of farms according to their geographical locations was observed. This study presents for the first time a genome-based analysis on the genetic structure of the two indigenous Greek goat breeds and identifies markers that can be potentially exploited in future selective breeding programs for traceability purposes, targeted genetic improvement schemes and conservation strategies