A multi-trait meta-analysis with imputed sequence variants reveals twelve QTL for mammary gland morphology in Fleckvieh cattle

Background The availability of whole-genome sequence data from key ancestors in bovine populations provides an exhaustive catalogue of polymorphic sites that segregate within and across cattle breeds. Sequence variants identified from the sequenced genome of key ancestors can be imputed into animals that have been genotyped using medium- and high-density genotyping arrays. Association analysis with imputed sequences, particularly when applied to multiple traits simultaneously, is a very powerful approach to detect candidate causal variants that underlie complex phenotypes. Results We used whole-genome sequence data from 157 key ancestors of the German Fleckvieh cattle population to impute 20,561,798 sequence variants into 10,363 animals that had (partly imputed) genotypes based on 634,109 single nucleotide polymorphisms (SNPs). Rare variants were more frequent among the sequence-derived than the array-derived genotypes. Association studies with imputed sequence variants were performed using seven correlated udder conformation traits as response variables. The calculation of an approximate multi-trait test statistic enabled us to detect 12 quantitative trait loci (QTL) (P < 2.97 × 10−9) that affect different morphological features of the mammary gland. Among the tested variants, the most significant associations were found for imputed sequence variants at 11 QTL, whereas the top association signal was observed for an array-derived variant at a QTL on bovine chromosome 14. Seven QTL were associated with multiple phenotypes. Most QTL were located in non-coding regions of the genome but in close proximity of candidate genes that could be involved in mammary gland morphology (SP5, GC, NPFFR2, CRIM1, RXFP2, TBX5, RBM19 and ADAM12). Conclusions Using imputed sequence variants in association analyses allows the detection of QTL at maximum resolution. Multi-trait approaches can reveal QTL that are not detected in single-trait association studies. Most QTL for udder conformation traits were located in non-coding regions of the genome, which suggests that mutations in regulatory sequences are the major determinants of variation in mammary gland morphology in cattle.ISSN:0999-193XISSN:1297-968

Radio Di Kawasan Perbatasan Indonesia Dalam Centering the Margin

Kawasan perbatasan Indonesia banyak mengalami blank spot layanan informasi sehingga siaran yang menghubungkan warganegara dan pemerintah tidak tersampaikan dengan baik. Padahal, keberadaan media di perbatasan sangat strategis sebagai penyedia informasi yang merefl eksikan dinamika lokal, mengartikulasikan kepentingan daerah sehingga dapat didengar oleh pusat. Harapannya, artikulasi tersebut dapat memberi warna pada dinamika sosial, politik, ekonomi, dan budaya di tanah air. Tulisan ini mengeksplorasi bagaimana radio di wilayah perbatasan memberikan kontribusi dalam peran centering the margin, yakni membawa aspirasi di perbatasan guna “memusatkan yang pinggir”

A Nonsense Mutation in TMEM95 Encoding a Nondescript Transmembrane Protein Causes Idiopathic Male Subfertility in Cattle

Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e.,idiopathic subfertility). Artificial insemination (AI) in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS). Imputed genotypes of 652, 856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV) population. Male reproductive ability (MRA) was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08x10(-59)). Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35, 671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome resequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c. 483C>A, p.Cys161X) in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic variation in TMEM95

Precision of genetic parameters and breeding values estimated in marker assisted BLUP genetic evaluation

In practical implementations of marker-assisted selection economic and logistic restrictions frequently lead to incomplete genotypic data for the animals of interest. This may result in bias and larger standard errors of the estimated parameters and, as a consequence, reduce the benefits of applying marker-assisted selection. Our study examines the impact of the following factors: phenotypic information, depth of pedigree, and missing genotypes in the application of marker-assisted selection. Stochastic simulations were conducted to generate a typical dairy cattle population. Genetic parameters and breeding values were estimated using a two-step approach. First, pre-corrected phenotypes (daughter yield deviations (DYD) for bulls, yield deviations (YD) for cows) were calculated in polygenic animal models for the entire population. These estimated phenotypes were then used in marker assisted BLUP (MA-BLUP) evaluations where only the genotyped animals and their close relatives were included

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

Multiple lactation random regression test-day model for Simmental and Brown Swiss in Germany and Austria

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