The 1000 bull genomes project supports the goal of accelerating the rates of genetic gain in domestic cattle while at the same time considering animal health and welfare by providing the annotated ...sequence variants and genotypes of key ancestor bulls. In the first phase of the 1000 bull genomes project, we sequenced the whole genomes of 234 cattle to an average of 8.3-fold coverage. This sequencing includes data for 129 individuals from the global Holstein-Friesian population, 43 individuals from the Fleckvieh breed and 15 individuals from the Jersey breed. We identified a total of 28.3 million variants, with an average of 1.44 heterozygous sites per kilobase for each individual. We demonstrate the use of this database in identifying a recessive mutation underlying embryonic death and a dominant mutation underlying lethal chrondrodysplasia. We also performed genome-wide association studies for milk production and curly coat, using imputed sequence variants, and identified variants associated with these traits in cattle.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 ...with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases.
In this study using the high density BovineHD SNP array, we performed high resolution CNV analyses on both Btau_4.0 and UMD3.1 with 674 animals of 27 cattle breeds. We first compared CNV results derived from these two different SNP array platforms on Btau_4.0. With two thirds of the animals shared between studies, on Btau_4.0 we identified 3,346 candidate CNV regions representing 142.7 megabases (~4.70%) of the genome. With a similar total length but 5 times more event counts, the average CNVR length of current Btau_4.0 dataset is significantly shorter than the previous one (42.7 kb vs. 205 kb). Although subsets of these two results overlapped, 64% (91.6 megabases) of current dataset was not present in the previous study. We also performed similar analyses on UMD3.1 using these BovineHD SNP array results. Approximately 50% more and 20% longer CNVs were called on UMD3.1 as compared to those on Btau_4.0. However, a comparable result of CNVRs (3,438 regions with a total length 146.9 megabases) was obtained. We suspect that these results are due to the UMD3.1 assembly's efforts of placing unplaced contigs and removing unmerged alleles. Selected CNVs were further experimentally validated, achieving a 73% PCR validation rate, which is considerably higher than the previous validation rate. About 20-45% of CNV regions overlapped with cattle RefSeq genes and Ensembl genes. Panther and IPA analyses indicated that these genes provide a wide spectrum of biological processes involving immune system, lipid metabolism, cell, organism and system development.
We present a comprehensive result of cattle CNVs at a higher resolution and sensitivity. We identified over 3,000 candidate CNV regions on both Btau_4.0 and UMD3.1, further compared current datasets with previous results, and examined the impacts of genome assemblies on CNV calling.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An enduring controversy exists about low milk cell counts and susceptibility to mastitis. The concentration of milk leukocytes, or somatic cell count (SCC), is a well-established direct indicator of ...mammary gland inflammation that is highly correlated with the presence of a mammary infection. The SCC is also used as a trait for the selection of dairy ruminants less prone to mastitis. As selection programs favor animals with less SCC, and as milk cells contribute to the defense of the mammary gland, the idea that susceptibility to mastitis could possibly be increased in the long term has been put forward and is still widely debated. Epidemiological and experimental studies aimed at relating SCC to susceptibility to mastitis have yielded results that seem contradictory at first sight. Nevertheless, by taking into account the immunobiology of milk and mammary tissue cells and their role in the defense against infection, along with recent studies on SCC-based divergent selection of animals, the issue can be settled. Apparent SCC-linked susceptibility to mastitis is a phenotypic trait that may be linked to immunomodulation but not to selection.
Cattle production faces new challenges regarding sustainability with its three pillars - economic, societal and environmental. The following three main factors will drive dairy cattle selection in ...the future: (1) During a long period, intensive selection for enhanced productivity has deteriorated most functional traits, some reaching a critical point and needing to be restored. This is especially the case for the Holstein breed and for female fertility, mastitis resistance, longevity and metabolic diseases. (2) Genomic selection offers two new opportunities: as the potential genetic gain can be almost doubled, more traits can be efficiently selected; phenotype recording can be decoupled from selection and limited to several thousand animals. (3) Additional information from other traits can be used, either from existing traditional recording systems at the farm level or from the recent and rapid development of new technologies and precision farming. Milk composition (i.e. mainly fatty acids) should be adapted to better meet human nutritional requirements. Fatty acids can be measured through a new interpretation of the usual medium infrared spectra. Milk composition can also provide additional information about reproduction and health. Modern milk recorders also provide new information, that is, on milking speed or on the shape of milking curves. Electronic devices measuring physiological or activity parameters can predict physiological status like estrus or diseases, and can record behavioral traits. Slaughterhouse data may permit effective selection on carcass traits. Efficient observatories should be set up for early detection of new emerging genetic defects. In the near future, social acceptance of cattle production could depend on its capacity to decrease its ecological footprint. The first solution consists in increasing survival and longevity to reduce replacement needs and the number of nonproductive animals. At the individual level, selection on rumen activity may lead to decreased methane production and concomitantly to improved feed efficiency. A major effort should be dedicated to this new field of research and particularly to rumen flora metagenomics. Low input in cattle production is very important and tomorrow's cow will need to adapt to a less intensive production environment, particularly lower feed quality and limited care. Finally, global climate change will increase pathogen pressure, thus more accurate predictors for disease resistance will be required.
This study investigated the effect on the reliability of genomic prediction when a small number of significant variants from single marker analysis based on whole genome sequence data were added to ...the regular 54k single nucleotide polymorphism (SNP) array data. The extra markers were selected with the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit index itself. Depending on the trait’s economic weight, 15, 10, or 5 quantitative trait loci (QTL) were selected per trait per breed and 3 to 5 markers were selected to tag each QTL. After removing duplicate markers (same marker selected for more than one trait or breed) and filtering for high pairwise linkage disequilibrium and assaying performance on the array, a total of 1,623 QTL markers were selected for inclusion on the custom chip. Genomic prediction analyses were performed for Nordic and French Holstein and Nordic Red animals using either a genomic BLUP or a Bayesian variable selection model. When using the genomic BLUP model including the QTL markers in the analysis, reliability was increased by up to 4 percentage points for production traits in Nordic Holstein animals, up to 3 percentage points for Nordic Reds, and up to 5 percentage points for French Holstein. Smaller gains of up to 1 percentage point was observed for mastitis, but only a 0.5 percentage point increase was seen for fertility. When using a Bayesian model accuracies were generally higher with only 54k data compared with the genomic BLUP approach, but increases in reliability were relatively smaller when QTL markers were included. Results from this study indicate that the reliability of genomic prediction can be increased by including markers significant in genome-wide association studies on whole genome sequence data alongside the 54k SNP set.
Body condition score (BCS) offers a good estimate of the amount of stored fat on the body, and its variations can be used as a proxy for energy balance. Many countries have implemented a genomic ...evaluation of BCS, including France, where estimated breeding values are based on an individual BCS determination during the first lactation. In this article, we investigate the degree to which this genomic estimated breeding value based on a single phenotype record per cow might reflect different profiles of body reserves throughout lactation and be used to predict, and perhaps limit, their mobilization during early lactation. We also investigate whether selection on BCS affects other traits. A data set including 686 lactations of 435 Holstein cows from 3 experimental farms not used in the reference population for genomic evaluation was used to estimate the effects of the BCS direct genomic value (iBCS) on BCS, body weight, feed intake, milk production, and fat and protein contents throughout the lactation period. For each trait, the model included different iBCS regressions and an effect of the direct genomic value of the trait itself when available. It thus appeared that cows with a positive iBCS always had a higher BCS than negative iBCS cows, whatever the lactation stage, and that this difference increased during the first 6 mo to reach a difference of 0.8 point. A similar effect was seen regarding body weight, but it was the opposite for milk production, with negative iBCS cows producing slightly more milk (difference of about 3% over lactation). Feed intake increased slightly faster at the beginning of lactation for cows with positive iBCS. Therefore, iBCS is a promising tool that could help to limit intense mobilization during early lactation. Should feed efficiency be included in the breeding goal, greater attention should be paid to BCS to avoid further body mobilization in early lactation.
The mineral composition of bovine milk plays an important role in determining its nutritional and cheese-making value. Concentrations of the main minerals predicted from mid-infrared spectra produced ...during milk recording, combined with cow genotypes, provide a unique opportunity to decipher the genetic determinism of these traits. The present study included 1 million test-day predictions of Ca, Mg, P, K, Na, and citrate content from 126,876 Montbéliarde cows, of which 19,586 had genotype data available. All investigated traits were highly heritable (0.50-0.58), with the exception of Na (0.32). A sequence-based genome-wide association study (GWAS) detected 50 QTL (18 affecting two to five traits) and positional candidate genes and variants, mostly located in non-coding sequences. In silico post-GWAS analyses highlighted 877 variants that could be regulatory SNPs altering transcription factor (TF) binding sites or located in non-coding RNA (mainly lncRNA). Furthermore, we found 47 positional candidate genes and 45 TFs highly expressed in mammary gland compared to 90 other bovine tissues. Among the mammary-specific genes, SLC37A1 and ANKH, encoding proteins involved in ion transport were located in the most significant QTL. This study therefore highlights a comprehensive set of functional candidate genes and variants that affect milk mineral content.
Cet article présente une simulation de sélection génomique dans une grande population de bovins laitiers en comparaison à un programme basé sur le testage des taureaux sur descendance. ...L’accroissement de progrès génétique est maximum (au moins 80% sans augmentation de coût) quand les pères à taureaux, dont les effectifs sont en forte augmentation, sont sélectionnés uniquement sur information génomique, sans testage sur descendance. Avec ce nombre élevé de pères à taureaux, les coefficients de consanguinité et de parenté diminuent, contrairement à ce qu’on aurait pu craindre compte tenu du raccourcissement de l’intervalle entre générations. Au niveau des éleveurs, la recommandation est de choisir les taureaux d’insémination de service (pères des femelles) en nombre suffisant dans l’ensemble des nombreux pères à taureaux génomiques, en opposition complète avec la pratique générale qui, jusqu’en 2009, consistait au contraire à sélectionner un nombre relativement réduit de taureaux de service parmi les taureaux testés et un nombre encore plus faible de pères à taureaux parmi les taureaux de service. Ces résultats, obtenus en 2009, ont jeté les bases de la gestion des populations bovines laitières en France en sélection génomique, mais ils restent tout à fait d’actualité aujourd’hui. Il est en effet essentiel pour la durabilité de la sélection et de la production que le nombre efficace de reproducteurs soit élevé pour limiter l’augmentation de la consanguinité. L’observation des premières années d’application montre que ces préconisations sont relativement bien suivies en moyenne.
Genomic selection was simulated in a large dairy cattle population in comparison with a breeding scheme based on bull progeny-testing. The maximum increase of genetic gain (about 80% without cost increase) was obtained when bull sires, in much larger number, were selected only based on genomic information, without progeny-testing. In spite of a shorter generation interval, annual inbreeding and coancestry rates were decreased because these bull sires were much more numerous than in the reference scheme. The general recommendation to the AI industry is to pick-up a quite large batch of commercial sires (for breeding regular females) within the set of genomic bull sires, in total contrast with the conventional practice where few bull sires are a selected set of commercial sires, themselves in limited number because selected after progeny-testing. These results obtained in 2009 paved the way for a sustainable genomic selection of French dairy cattle, and are still up to date. Indeed, it is critical for selection and dairy cattle production sustainability to maintain a high enough effective size of the breeds to limit the inbreeding trend. An overview of the first years of activity shows that these recommendations have been well respected on average.
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