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1.
    
A genome‐wide association study (GWAS) was conducted on 15 milk production traits in Chinese Holstein. The experimental population consisted of 445 cattle, each genotyped by the GGP (GeneSeek genomic profiling)‐BovineLD V3 SNP chip, which had 26 151 public SNPs in its manifest file. After data cleaning, 20 326 SNPs were retained for the GWAS. The phenotypes were estimated breeding values of traits, provided by a public dairy herd improvement program center that had been collected once a month for 3 years. Two statistical models, a fixed‐effect linear regression model and a mixed‐effect linear model, were used to estimate the association effects of SNPs on each of the phenotypes. Genome‐wide significant and suggestive thresholds were set at 2.46E‐06 and 4.95E‐05 respectively. The two statistical models concurrently identified two genome‐wide significant (< 0.05) SNPs on milk production traits in this Chinese Holstein population. The positional candidate genes, which were the ones closest to these two identified SNPs, were EEF2K (eukaryotic elongation factor 2 kinase) and KLHL1 (kelch like family member 1). These two genes could serve as new candidate genes for milk yield and lactation persistence, yet their roles need to be verified in further function studies.  相似文献   

2.
    
Because of increasing litter size in Western pig breeds, additional teats are desirable to increase the capacity for nursing offspring. We applied genome‐wide SNP markers to detect QTL regions that affect teat number in a Duroc population. We phenotyped 1024 animals for total teat number. A total of 36 588 SNPs on autosomes were used in the analysis. The estimated heritability for teat number was 0.34 ± 0.05 on the basis of a genomic relationship matrix constructed from all SNP markers. Using a BayesC method, we identified a total of 18 QTL regions that affected teat number in Duroc pigs; 9 of the 18 regions were newly detected.  相似文献   

3.
    
Marginal tests based on individual SNPs are routinely used in genetic association studies. Studies have shown that haplotype‐based methods may provide more power in disease mapping than methods based on single markers when, for example, multiple disease‐susceptibility variants occur within the same gene. A limitation of haplotype‐based methods is that the number of parameters increases exponentially with the number of SNPs, inducing a commensurate increase in the degrees of freedom and weakening the power to detect associations. To address this limitation, we introduce a hierarchical linkage disequilibrium model for disease mapping, based on a reparametrization of the multinomial haplotype distribution, where every parameter corresponds to the cumulant of each possible subset of a set of loci. This hierarchy present in the parameters enables us to employ flexible testing strategies over a range of parameter sets: from standard single SNP analyses through the full haplotype distribution tests, reducing degrees of freedom and increasing the power to detect associations. We show via extensive simulations that our approach maintains the type I error at nominal level and has increased power under many realistic scenarios, as compared to single SNP and standard haplotype‐based studies. To evaluate the performance of our proposed methodology in real data, we analyze genome‐wide data from the Wellcome Trust Case‐Control Consortium.  相似文献   

4.
    
Animal growth relative to food energy input is of key importance to agricultural production. Several recent studies highlighted genetic markers associated with food conversion efficiency in beef cattle, and there is now a requirement to validate these associations in additional populations and to assess their potential utility for selecting animals with enhanced food‐use efficiency. The current analysis tested a population of dairy cattle using 138 DNA markers previously associated with food intake and growth in a whole‐genome association analysis of beef animals. Although seven markers showed point‐wise significance at P < 0.05, none of the single‐nucleotide polymorphisms tested were significantly associated with food conversion efficiency after correction for multiple testing. These data do not support the involvement of this subset of previously implicated markers in the food conversion efficiency of the physiologically distinct New Zealand Holstein‐Friesian dairy breed.  相似文献   

5.
    
Recurrent exertional rhabdomyolysis is a heritable disorder that results in painful skeletal muscle cramping with exercise in up to 10% of all Thoroughbred racehorses. Here, we report a genome‐wide association study with 48 282 SNPs analyzed among 48 case and 37 control Thoroughbreds. The most significant SNPs spanned approximately 13 Mb on ECA16, and the P‐value of the most significant SNP after correcting for population structure was 8.0 × 10?6. This region on ECA16 was further evaluated by genotyping 247 SNPs in both the initial population and a second population of 34 case and 98 control Thoroughbreds. Several SNPs across the 13‐Mb region on ECA16 showed significance when each population was analyzed separately; however, the exact positions of the most significant SNPs within this region on ECA16 varied between populations. This variability in location may be attributed to lack of power owing to insufficient sample sizes within each population individually, or to the relative distribution of long, conserved haplotypes, characteristic of the Thoroughbred breed. Future genome‐wide association studies with additional horses would likely improve the power to resolve casual loci located on ECA16 and increase the likelihood of detecting any additional loci on other chromosomes contributing to disease susceptibility.  相似文献   

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8.
    
Four‐horned sheep are an ideal animal model for illuminating the genetic basis of horn development. The objective of this study was to locate the genetic region responsible for the four‐horned phenotype and to verify a previously reported polled locus in three Chinese breeds. A genome‐wide association study (GWAS) was performed using 34 two‐horned and 32 four‐horned sheep from three Chinese indigenous breeds: Altay, Mongolian and Sishui Fur sheep. The top two significant single nucleotide polymorphisms (SNPs) associated with the four‐horned phenotype were both located in a region spanning positions 132.6 to 132.7 Mb on sheep chromosome 2. Similar locations for the four‐horned trait were previously identified in Jacob, Navajo‐Churro, Damara and Sishui Fur sheep, suggesting a common genetic component underlying the four‐horned phenotype. The two identified SNPs were both downstream of the metaxin 2 (MTX2) gene and the HOXD gene cluster. For the top SNP—OAR2:g.132619300G>A—the strong associations of the AA and AG genotypes with the four‐horned phenotype and the GG genotype with the two‐horned phenotype indicated the dominant inheritance of the four‐horned trait. No significant SNPs for the polled phenotype were identified in the GWAS analysis, and a PCR analysis for the detection of the 1.8‐kb insertion associated with polled sheep in other breeds failed to verify the association with polledness in the three Chinese breeds. This study supports the hypothesis that two different loci are responsible for horn existence and number. This study contributes to the understanding of the molecular regulation of horn development and enriches the knowledge of qualitative traits in domestic animals.  相似文献   

9.
    
A genome‐wide association study of 2098 progeny‐tested Nordic Holstein bulls genotyped for 36 387 SNPs on 29 autosomes was conducted to confirm and fine‐map quantitative trait loci (QTL) for mastitis traits identified earlier using linkage analysis with sparse microsatellite markers in the same population. We used linear mixed model analysis where a polygenic genetic effect was fitted as a random effect and single SNPs were successively included as fixed effects in the model. We detected 143 SNP‐by‐trait significant associations (P < 0.0001) on 20 chromosomes affecting mastitis‐related traits. Among them, 21 SNP‐by‐trait combinations exceeded the genome‐wide significant threshold. For 12 chromosomes, both the present association study and the previous linkage study detected QTL, and of these, six were in the same chromosomal locations. Strong associations of SNPs with mastitis traits were observed on bovine autosomes 6, 13, 14 and 20. Possible candidate genes for these QTL were identified. Identification of SNPs in linkage disequilibrium with QTL will enable marker‐based selection for mastitis resistance. The candidate genes identified should be further studied to detect candidate polymorphisms underlying these QTL.  相似文献   

10.
    
The marriage of metabolomic approaches with genetic design has proven a powerful tool in dissecting diversity in the metabolome and has additionally enhanced our understanding of complex traits. That said, such studies have rarely been carried out in wheat. In this study, we detected 805 metabolites from wheat kernels and profiled their relative contents among 182 wheat accessions, conducting a metabolite‐based genome‐wide association study (mGWAS) utilizing 14 646 previously described polymorphic SNP markers. A total of 1098 mGWAS associations were detected with large effects, within which 26 candidate genes were tentatively designated for 42 loci. Enzymatic assay of two candidates indicated they could catalyse glucosylation and subsequent malonylation of various flavonoids and thereby the major flavonoid decoration pathway of wheat kernel was dissected. Moreover, numerous high‐confidence genes associated with metabolite contents have been provided, as well as more subdivided metabolite networks which are yet to be explored within our data. These combined efforts presented the first step towards realizing metabolomics‐associated breeding of wheat.  相似文献   

11.
    
Adaptation to early training and racing (i.e. precocity), which is highly variable in racing Thoroughbreds, has implications for the selection and training of horses. We hypothesised that precocity in Thoroughbred racehorses is heritable. Age at first sprint training session (work day), age at first race and age at best race were used as phenotypes to quantify precocity. Using high‐density SNP array data, additive SNP heritability () was estimated to be 0.17, 0.14 and 0.17 for the three traits respectively. In genome‐wide association studies (GWAS) for age at first race and age at best race, a 1.98‐Mb region on equine chromosome 18 (ECA18) was identified. The most significant association was with the myostatin (MSTN) g.66493737C>T SNP (= 5.46 × 10?12 and = 1.89 × 10?14 respectively). In addition, two SNPs on ECA1 (g.37770220G>A and g.37770305T>C) within the first intron of the serotonin receptor gene HTR7 were significantly associated with age at first race and age at best race. Although no significant associations were identified for age at first work day, the MSTN:g.66493737C>T SNP was among the top 20 SNPs in the GWAS (= 3.98 × 10?5). Here we have identified variants with potential roles in early adaptation to training. Although there was an overlap in genes associated with precocity and distance aptitude (i.e. MSTN), the HTR7 variants were more strongly associated with precocity than with distance. Because HTR7 is closely related to the HTR1A gene, previously implicated in tractability in young Thoroughbreds, this suggests that behavioural traits may influence precocity.  相似文献   

12.
    
The Tibetan chicken (TBC), an indigenous chicken breed of the Tibetan Plateau, has adapted to its hypoxic, high‐altitude environment over hundreds of years. The objective of this study was to identify the polymorphisms and genes associated with adaptation to hypoxia in this chicken breed. In the present study, samples were collected during days 18–21 of the incubation period from both surviving chicks and dead embryos, all of which were hatched under hypoxic conditions. A genome‐wide association study was conducted using the Illumina iSelect 60K SNP array with a case–control design, in which the case group consisted of the dead chicken embryos (= 54) and controls were the surviving chicks (= 82). Four significant SNPs were detected at the genome‐wide level (< 0.05), and the results indicated that fork head box G1 (FOXG1) was the main candidate gene. The lead SNP NC_006092.4:g.33368893T>C was confirmed with a polymerase chain reaction‐restriction fragment length polymorphism analysis of 122 cases and 212 controls. A chi‐square test showed a significant association between NC_006092.4:g.33368893T>C and hatchability under hypoxic conditions (< 0.01). Our results revealed novel polymorphisms and a candidate gene associated with hypoxic adaptation, facilitating further study in this field.  相似文献   

13.
    
Maize (Zea mays mays) oil is a rich source of polyunsaturated fatty acids (FAs) and energy, making it a valuable resource for human food, animal feed, and bio‐energy. Although this trait has been studied via conventional genome‐wide association study (GWAS), the single nucleotide polymorphism (SNP)‐trait associations generated by GWAS may miss the underlying associations when traits are based on many genes, each with small effects that can be overshadowed by genetic background and environmental variation. Detecting these SNPs statistically is also limited by the levels set for false discovery rate. A complementary pathways analysis that emphasizes the cumulative aspects of SNP‐trait associations, rather than just the significance of single SNPs, was performed to understand the balance of lipid metabolism, conversion, and catabolism in this study. This pathway analysis indicated that acyl‐lipid pathways, including biosynthesis of wax esters, sphingolipids, phospholipids and flavonoids, along with FA and triacylglycerol (TAG) biosynthesis, were important for increasing oil and FA content. The allelic variation found among the genes involved in many degradation pathways, and many biosynthesis pathways leading from FAs and carbon partitioning pathways, was critical for determining final FA content, changing FA ratios and, ultimately, to final oil content. The pathways and pathway networks identified in this study, and especially the acyl‐lipid associated pathways identified beyond what had been found with GWAS alone, provide a real opportunity to precisely and efficiently manipulate high‐oil maize genetic improvement.  相似文献   

14.
    
L. Yang  X. Du  S. Wei  L. Gu  N. Li  Y. Gong  S. Li 《Animal genetics》2017,48(5):611-614
Plumage color in chicken is determined by the proportion of eumelanin and pheomelanin pigmentation. As the main ingredient in plumage melanin, eumelanin plays a key role in the dark black, brown and grey coloration. However, very few studies have been performed to identify the related genes and mutations on a genome‐wide scale. Herein, a resource family consisting of one backcross population and two F2 cross populations between a black roster and Yukou Brown I parent stockbreed was constructed for identification of genes related to eumelanin pigmentation. Chickens with eumelanin in their plumage were classified as the case group, and the rest were considered the control group. A genome‐wide association study of this phenotype and genotypes using Affymetrix 600K HD SNP arrays in this F2 family revealed 13 significantly associated SNPs and in 10 separate genes on chromosomes 1, 2, 3 and 5. Based on previous studies in model species, we inferred that genes, including NUAK family kinase 1 (NUAK1) and sonic hedgehog (SHH), may play roles in the development of neural crest cells or melanoblasts during the embryonic period, which may also affect the eumelanin pigmentation. Our results facilitate the understanding of the genetic basis of eumelanin pigmentation in chicken plumage.  相似文献   

15.
    
The presence of congenital appendages (wattles) on the throat of goats is supposed to be under genetic control with a dominant mode of inheritance. Wattles contain a cartilaginous core covered with normal skin resembling early stages of extremities. To map the dominant caprine wattles (W) locus, we collected samples of 174 goats with wattles and 167 goats without wattles from nine different Swiss goat breeds. The samples were genotyped with the 53k goat SNP chip for a subsequent genome‐wide association study. We obtained a single strong association signal on chromosome 10 in a region containing functional candidate genes for limb development and outgrowth. We sequenced the whole genomes of an informative family trio containing an offspring without wattles and its heterozygous parents with wattles. In the associated goat chromosome 10 region, a total of 1055 SNPs and short indels perfectly co‐segregate with the W allele. None of the variants were perfectly associated with the phenotype after analyzing the genome sequences of eight additional goats. We speculate that the causative mutation is located in one of the numerous gaps in the current version of the goat reference sequence and/or represents a larger structural variant which influences the expression of the FMN1 and/or GREM1 genes. Also, we cannot rule out possible genetic or allelic heterogeneity. Our genetic findings support earlier assumptions that wattles are rudimentary developed extremities.  相似文献   

16.
    
Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non‐additive genetic variation, we present an approach using genome‐wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein–Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome‐wide markers were tested for associations between heterozygosity and bTB status using marker‐based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy‐Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome‐wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (< 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (< 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy‐number‐variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large‐scale data.  相似文献   

17.
Improving immune capacity may increase the profitability of animal production if it enables animals to better cope with infections. Hematological traits play pivotal roles in animal immune capacity and disease resistance. Thus far, few studies have been conducted using a high‐density swine SNP chip panel to unravel the genetic mechanism of the immune capability in domestic animals. In this study, using mixed model‐based single‐locus regression analyses, we carried out genome‐wide association studies, using the Porcine SNP60 BeadChip, for immune responses in piglets for 18 hematological traits (seven leukocyte traits, seven erythrocyte traits, and four platelet traits) after being immunized with classical swine fever vaccine. After adjusting for multiple testing based on permutations, 10, 24, and 77 chromosome‐wise significant SNPs were identified for the leukocyte traits, erythrocyte traits, and platelet traits respectively, of which 10 reached genome‐wise significance level. Among the 53 SNPs for mean platelet volume, 29 are located in a linkage disequilibrium block between 32.77 and 40.59 Mb on SSC6. Four genes of interest are located within the block, providing genetic evidence that this genomic segment may be considered a candidate region relevant to the platelet traits. Other candidate genes of interest for red blood cell, hemoglobin, and red blood cell volume distribution width also have been found near the significant SNPs. Our genome‐wide association study provides a list of significant SNPs and candidate genes that offer valuable information for future dissection of molecular mechanisms regulating hematological traits.  相似文献   

18.
    
Bovine leukosis virus is an oncogenic virus that infects B cells, causing bovine leukosis disease. This disease is known to have a negative impact on dairy cattle production and, because no treatment or vaccine is available, finding a possible genetic solution is important. Our objective was to perform a comprehensive genetic analysis of leukosis incidence in dairy cattle. Data on leukosis occurrence, pedigree and molecular information were combined into multitrait GBLUP models with milk yield (MY) and somatic cell score (SCS) to estimate genetic parameters and to perform whole‐genome scans and pathway analysis. Leukosis data were available for 11 554 Holsteins daughters of 3002 sires from 112 herds in 16 US states. Genotypes from a 60K SNP panel were available for 961 of those bulls as well as for 2039 additional bulls. Heritability for leukosis incidence was estimated at about 8%, and the genetic correlations of leukosis disease incidence with MY and SCS were moderate at 0.18 and 0.20 respectively. The genome‐wide scan indicated that leukosis is a complex trait, possibly modulated by many genes. The gene set analysis identified many functional terms that showed significant enrichment of genes associated with leukosis. Many of these terms, such as G‐Protein Coupled Receptor Signaling Pathway, Regulation of Nucleotide Metabolic Process and different calcium‐related processes, are known to be related to retrovirus infection. Overall, our findings contribute to a better understanding of the genetic architecture of this complex disease. The functional categories associated with leukosis may be useful in future studies on fine mapping of genes and development of dairy cattle breeding strategies.  相似文献   

19.
SNP(single nucleotide polymorphism,单核苷酸多态)在猪基因组中的分布极其广泛,平均分布间隔为300~400 bp,相关数据库收录已达55万条。猪基因组测序已取得实质性进展,大规模搜索发现基因组及EST(expressed sequence tag)序列中的SNP已展开,应用于猪全基因组水平的SNP芯片已建立。在此基础上,基于猪SNP标记的遗传图谱绘制、QTL(quantitative trait loci)定位、遗传多样性检测及全基因组关联分析等也都相继出现。  相似文献   

20.
    
A specific white spotting phenotype, termed finching or line‐backed spotting, is known for all Pinzgauer cattle and occurs occasionally in Tux‐Zillertaler cattle, two Austrian breeds. The so‐called Pinzgauer spotting is inherited as an autosomal incompletely dominant trait. A genome‐wide association study using 27 white spotted and 16 solid‐coloured Tux‐Zillertaler cattle, based on 777k SNP data, revealed a strong signal on chromosome 6 at the KIT locus. Haplotype analyses defined a critical interval of 122 kb downstream of the KIT coding region. Whole‐genome sequencing of a Pinzgauer cattle and comparison to 338 control genomes revealed a complex structural variant consisting of a 9.4‐kb deletion and an inversely inserted duplication of 1.5 kb fused to a 310‐kb duplicated segment from chromosome 4. A diagnostic PCR was developed for straightforward genotyping of carriers for this structural variant (KITPINZ) and confirmed that the variant allele was present in all Pinzgauer and most of the white spotted Tux‐Zillertaler cattle. In addition, we detected the variant in all Slovenian Cika, British Gloucester and Spanish Berrenda en negro cattle with similar spotting patterns. Interestingly, the KITPINZ variant occurs in some white spotted animals of the Swiss breeds Evolèner and Eringer. The introgression of the KITPINZ variant confirms admixture and the reported historical relationship of these short‐headed breeds with Austrian Tux‐Zillertaler and suggests a mutation event, occurring before breed formation.  相似文献   

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