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DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle.

ABSTRACT: BACKGROUND: Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215) that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep). RESULTS: Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ? 0.01) were observed at four loci. Phenotypic associations (P ? 0.05) were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3) gene cluster were associated (P ? 0.05) with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215) was associated with milk protein percentage (P ? 0.05), progeny carcass weight (P ? 0.05), culled cow carcass weight (P ? 0.01), angularity (P ? 0.01), body depth (P ? 0.01), rump width (P ? 0.01) and animal stature (P ? 0.01). CONCLUSIONS: Of the eight candidate bovine imprinted genes assessed, DNA sequence polymorphisms in six of these genes (CALCR, GRB10, PEG3, RASGRF1, ZIM2 and ZNF215) displayed associations with several of the phenotypes included for analyses. The genotype-phenotype associations detected here are further supported by the biological function of these six genes, each of which plays important roles in mammalian growth, development and physiology. The associations between SNPs within the imprinted PEG3 gene cluster and traits related to calving, calf performance and gestation length suggest that this domain on chromosome 18 may play a role regulating pre-natal growth and development and fertility. SNPs within the bovine ZNF215 gene were associated with bovine growth and body conformation traits and studies in humans have revealed that the human ZNF215 ortholog belongs to the imprinted gene cluster associated with Beckwith-Wiedemann syndrome--a genetic disorder characterised by growth abnormalities. Similarly, the data presented here suggest that the ZNF215 gene may have an important role in regulating bovine growth. Collectively, our results support previous work showing that (candidate) imprinted genes/loci contribute to heritable variation in bovine performance traits and suggest that DNA sequence polymorphisms within these genes/loci represents an important reservoir of genomic markers for future genetic improvement of dairy and beef cattle populations.

SUBMITTER: Magee DA

PROVIDER: S-EPMC2965127 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle.

Magee David A DA Sikora Klaudia M KM Berkowicz Erik W EW Berry Donagh P DP Howard Dawn J DJ Mullen Michael P MP Evans Ross D RD Spillane Charles C MacHugh David E DE

BMC genetics 20101013

<h4>Background</h4>Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present stu ...[more]

PMID: 20942903

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Project description:BackgroundThe significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics.MethodsThe present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control.ResultsThe estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB.ConclusionGenomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.

Project description:BACKGROUND: Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. RESULTS: All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05). CONCLUSIONS: Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow.

Project description:BackgroundThe extent of linkage disequilibrium (LD) within a population determines the number of markers that will be required for successful association mapping and marker-assisted selection. Most studies on LD in cattle reported to date are based on microsatellite markers or small numbers of single nucleotide polymorphisms (SNPs) covering one or only a few chromosomes. This is the first comprehensive study on the extent of LD in cattle by analyzing data on 1,546 Holstein-Friesian bulls genotyped for 15,036 SNP markers covering all regions of all autosomes. Furthermore, most studies in cattle have used relatively small sample sizes and, consequently, may have had biased estimates of measures commonly used to describe LD. We examine minimum sample sizes required to estimate LD without bias and loss in accuracy. Finally, relatively little information is available on comparative LD structures including other mammalian species such as human and mouse, and we compare LD structure in cattle with public-domain data from both human and mouse.ResultsWe computed three LD estimates, D', Dvol and r2, for 1,566,890 syntenic SNP pairs and a sample of 365,400 non-syntenic pairs. Mean D' is 0.189 among syntenic SNPs, and 0.105 among non-syntenic SNPs; mean r2 is 0.024 among syntenic SNPs and 0.0032 among non-syntenic SNPs. All three measures of LD for syntenic pairs decline with distance; the decline is much steeper for r2 than for D' and Dvol. The value of D' and Dvol are quite similar. Significant LD in cattle extends to 40 kb (when estimated as r2) and 8.2 Mb (when estimated as D'). The mean values for LD at large physical distances are close to those for non-syntenic SNPs. Minor allelic frequency threshold affects the distribution and extent of LD. For unbiased and accurate estimates of LD across marker intervals spanning < 1 kb to > 50 Mb, minimum sample sizes of 400 (for D') and 75 (for r2) are required. The bias due to small samples sizes increases with inter-marker interval. LD in cattle is much less extensive than in a mouse population created from crossing inbred lines, and more extensive than in humans.ConclusionFor association mapping in Holstein-Friesian cattle, for a given design, at least one SNP is required for each 40 kb, giving a total requirement of at least 75,000 SNPs for a low power whole-genome scan (median r2 > 0.19) and up to 300,000 markers at 10 kb intervals for a high power genome scan (median r2 > 0.62). For estimation of LD by D' and Dvol with sufficient precision, a sample size of at least 400 is required, whereas for r2 a minimum sample of 75 is adequate.

Project description:BackgroundThe focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle.MethodsData from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (-maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models.Results and discussionOn average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (-maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (-maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence.ConclusionsFor the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (-maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions.

Project description:BackgroundInbreeding depression refers to the decrease in mean performance due to inbreeding. Inbreeding depression is caused by an increase in homozygosity and reduced expression of (on average) favourable dominance effects. Dominance effects and allele frequencies differ across loci, and consequently inbreeding depression is expected to differ along the genome. In this study, we investigated differences in inbreeding depression across the genome of Dutch Holstein Friesian cattle, by estimating dominance effects and effects of regions of homozygosity (ROH).MethodsGenotype (75 k) and phenotype data of 38,792 cows were used. For nine yield, fertility and udder health traits, GREML models were run to estimate genome-wide inbreeding depression and estimate additive, dominance and ROH variance components. For this purpose, we introduced a ROH-based relationship matrix. Additive, dominance and ROH effects per SNP were obtained through back-solving. In addition, a single SNP GWAS was performed to identify significant additive, dominance or ROH associations.ResultsGenome-wide inbreeding depression was observed for all yield, fertility and udder health traits. For example, a 1% increase in genome-wide homozygosity was associated with a decrease in 305-d milk yield of approximately 99 kg. For yield traits only, including dominance and ROH effects in the GREML model resulted in a better fit (P?<?0.05) than a model with only additive effects. After correcting for the effect of genome-wide homozygosity, dominance and ROH variance explained less than 1% of the phenotypic variance for all traits. Furthermore, dominance and ROH effects were distributed evenly along the genome. The most notable region with a favourable dominance effect for yield traits was on chromosome 5, but overall few regions with large favourable dominance effects and significant dominance associations were detected. No significant ROH-associations were found.ConclusionsInbreeding depression was distributed quite equally along the genome and was well captured by genome-wide homozygosity. These findings suggest that, based on 75 k SNP data, there is little benefit of accounting for region-specific inbreeding depression in selection schemes.

Dataset Information

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle.

Publications

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle.

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