Signatures of selection in Charolais beef cattle identified by genome‐wide analysis

Charolais cattle are one of the most important breeds for meat production worldwide; in México, its selection is mainly made by live weight traits. One strategy for mapping important genomic regions that might influence productive traits is the identification of signatures of selection. This type of genomic features contains loci with extended linkage disequilibrium (LD) and homozygosity patterns that are commonly associated with sites of quantitative trait locus (QTL). Therefore, the objective of this study was to identify the signatures of selection in Charolais cattle genotyped with the GeneSeek Genomic Profiler Bovine HD panel consisting of 77 K single nucleotide polymorphisms (SNPs). A total 61,311 SNPs and 819 samples were used for the analysis. Identification of signatures of selection was carried out using the integrated haplotype score (iHS) methodology implemented in the rehh R package. The top ten SNPs with the highest piHS values were located on BTA 4, 5, 6 and 14. By identifying markers in LD with top ten SNPs, the candidate regions defined were mapped to 52.8–59.3 Mb on BTA 4; 67.5–69.3 on BTA 5; 39.5–41.0 Mb on BTA 6; and 26.4–29.6 Mb on BTA 14. The comparison of these candidate regions with the bovine QTLdb effectively confirmed the association (p < 0.05) with QTL related to growth traits and other important productive traits. The genomic regions identified in this study indicated selection for growth traits on the Charolais population via the conservation of haplotypes on various chromosomes. These genomic regions and their associated genes could serve as the basis for haplotype association studies and for the identification of causal genes related to growth traits.     

Detection of selection signatures for agonistic behaviour in cattle

The identification of genomic regions including signatures of selection produced by domestication and its subsequent artificial selection processes allows the understanding of the evolution of bovine breeds. Although several studies describe the genomic variability among meat or milk production cattle breeds, there are limited studies orientated towards bovine behavioural features. This study is focused on mapping genomic signatures of selection which may provide insights of differentiation between neutral and selected polymorphisms. Their effects are studied in the Lidia cattle traditionally selected for agonistic behaviour compared with Spanish breeds showing tamed behaviour. Two different approaches, BayeScan and SelEstim, were applied using genotypic 50K SNP BeadChip data. Both procedures detected two genomic regions bearing genes previously related to behavioural traits. The frequencies of the selected allele in these two regions in Lidia breed were opposite to those found in the tamed breeds. In these genomic regions, several putative genes associated with enriched metabolic pathways related to the behavioural development were identified, as neurochondrin gene (NCDN) or glutamate ionotropic receptor kainate type subunit 3 (GRIK3) both located at BTA3 or leucine‐rich repeat and Ig domain containing 2 (LINGO2) and phospholipase A2‐activating protein (PLAA) at BTA8.     

A genome‐wide association study for fat‐related traits computed by image analysis in Japanese Black cattle

The objective of this study was to identify genomic regions associated with fat‐related traits using a Japanese Black cattle population in Hyogo. From 1836 animals, those with high or low values were selected on the basis of corrected phenotype and then pooled into high and low groups (n = 100 each), respectively. DNA pool‐based genome‐wide association study (GWAS) was performed using Illumina BovineSNP50 BeadChip v2 with three replicate assays for each pooled sample. GWAS detected that two single nucleotide polymorphisms (SNPs) on BTA7 (ARS‐BFGL‐NGS‐35463 and Hapmap23838‐BTA‐163815) and one SNP on BTA12 (ARS‐BFGL‐NGS‐2915) significantly affected fat percentage (FAR). The significance of ARS‐BFGL‐NGS‐35463 on BTA7 was confirmed by individual genotyping in all pooled samples. Moreover, association analysis between SNP and FAR in 803 Japanese Black cattle revealed a significant effect of SNP on FAR. Thus, further investigation of these regions is required to identify FAR‐associated genes and mutations, which can lead to the development of DNA markers for marker‐assisted selection for the genetic improvement of beef quality.     

Genome-wide association studies of female reproduction in tropically adapted beef cattle

The genetics of reproduction is poorly understood because the heritabilities of traits currently recorded are low. To elucidate the genetics underlying reproduction in beef cattle, we performed a genome-wide association study using the bovine SNP50 chip in 2 tropically adapted beef cattle breeds, Brahman and Tropical Composite. Here we present the results for 3 female reproduction traits: 1) age at puberty, defined as age in days at first observed corpus luteum (CL) after frequent ovarian ultrasound scans (AGECL); 2) the postpartum anestrous interval, measured as the number of days from calving to first ovulation postpartum (first rebreeding interval, PPAI); and 3) the occurrence of the first postpartum ovulation before weaning in the first rebreeding period (PW), defined from PPAI. In addition, correlated traits such as BW, height, serum IGF1 concentration, condition score, and fatness were also examined. In the Brahman and Tropical Composite cattle, 169 [false positive rate (FPR) = 0.262] and 84 (FPR = 0.581) SNP, respectively, were significant (P < 0.001) for AGECL. In Brahman, 41% of these significant markers mapped to a single chromosomal region on BTA14. In Tropical Composites, 16% of these significant markers were located on BTA5. For PPAI, 66 (FPR = 0.67) and 113 (FPR = 0.432) SNP were significant (P < 0.001) in Brahman and Tropical Composite, respectively, whereas for PW, 68 (FPR = 0.64) and 113 (FPR = 0.432) SNP were significant (P < 0.01). In Tropical Composites, the largest concentration of PPAI markers were located on BTA5 [19% (PPAI) and 23% (PW)], and BTA16 [17% (PPAI) and 18% (PW)]. In Brahman cattle, the largest concentration of markers for postpartum anestrus was located on BTA3 (14% for PPAI and PW) and BTA14 (17% PPAI). Very few of the significant markers for female reproduction traits for the Brahman and Tropical Composite breeds were located in the same chromosomal regions. However, fatness and BW traits as well as serum IGF1 concentration were found to be associated with similar genome regions within and between breeds. Clusters of SNP associated with multiple traits were located on BTA14 in Brahman and BTA5 in Tropical Composites.     

Genome‐wide association study for fatty acid composition in Japanese Black cattle

Fatty acid composition is one of the important traits in beef. The aim of this study was to identify candidate genomic regions for fatty acid composition by genome‐wide association study with 50 K single nucleotide polymorphism (SNP) array in Japanese Black cattle. A total of 461 individuals and 40 657 SNPs were used in this study. We applied genome‐wide rapid association using mixed model and regression (GRAMMAR) and genomic control approaches to estimate the associations between genotypes and fatty acid composition. In addition, two SNPs in fatty acid synthase (FASN) (T1952A) and stearoyl‐CoA desaturase (SCD) (V293A) genes were also genotyped. Association analysis revealed that 30 significant SNPs for several fatty acids (C14:0, C14:1, C16:1 and C18:1) were located in the BTA19 FASN gene located within this region but the FASN mutation had no significant effect on any traits. We also detected one significant SNP for C18:1 on BTA23 and two SNPs for C16:0 on BTA25. The region around 17 Mb on BTA26 harbored two significant SNPs for C14:1 and SNP in SCD in this region showed the strongest association with C14:1. This study demonstrated novel candidate regions in BTA19, 23 and 25 for fatty acid composition.     

Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10(-5). In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type.     

Quantitative trait loci analysis for growth and carcass traits in a half-sib family of purebred Japanese Black (Wagyu) cattle

We used a half-sib family of purebred Japanese Black (Wagyu) cattle to locate economically important quantitative trait loci. The family was composed of 348 fattened steers, 236 of which were genotyped for 342 microsatellite markers spanning 2,664 cM of 29 bovine autosomes. The genome scan revealed evidence of 15 significant QTL (<5% chromosome-wise level) affecting growth and carcass traits. Of the 15 QTL, six QTL were significant at the 5% experiment-wise level and were located in bovine chromosomes (BTA) 4, 5, and 14. We analyzed these three chromosomes in more detail in the 348 steers, with an average marker interval of 1.2 cM. The second scan revealed that the same haplotype of the BTA 4 region (52 to 67 cM) positively affected LM area and marbling. We confirmed the QTL for carcass yield estimate on BTA 5 in the region of 45 to 54 cM. Five growth-related QTL located on BTA 14, including slaughter and carcass weights, were positively affected by the same region of the haplotype of BTA 14 (29-51 cM). These data should provide a useful reference for further marker-assisted selection in the family and positional cloning research. The research indicates that progeny design with moderate genotyping efforts is a powerful method for detecting QTL in a purebred half-sib family.     

Genome-wide detection of signatures of selection in three Valdostana cattle populations

The Valdostana is a local dual purpose cattle breed developed in Italy. Three populations are recognized within this breed, based on coat colour, production level, morphology and temperament: Valdostana Red Pied (VPR), Valdostana Black Pied (VPN) and Valdostana Chestnut (VCA). Here, we investigated putative genomic regions under selection among these three populations using the Bovine 50K SNP array by combining three different statistical methods based either on allele frequencies (F_ST) or extended haplotype homozygosity (iHS and Rsb). In total, 8, 5 and 8 chromosomes harbouring 13, 13 and 16 genomic regions potentially under selection were identified by at least two approaches in VPR, VPN and VCA, respectively. Most of these candidate regions were population-specific but we found one common genomic region spanning 2.38 Mb on BTA06 which either overlaps or is located close to runs of homozygosity islands detected in the three populations. This region included inter alia two well-known genes: KDR, a well-established coat colour gene, and CLOCK, which plays a central role in positive regulation of inflammatory response and in the regulation of the mammalian circadian rhythm. The other candidate regions identified harboured genes associated mainly with milk and meat traits as well as genes involved in immune response/inflammation or associated with behavioural traits. This last category of genes was mainly identified in VCA, which is selected for fighting ability. Overall, our results provide, for the first time, a glimpse into regions of the genome targeted by selection in Valdostana cattle. Finally, this study illustrates the relevance of using multiple complementary approaches to identify genomic regions putatively under selection in livestock.     

Candidate genes for male and female reproductive traits in Canchim beef cattle

Background: Beef cattle breeding programs in Brazil have placed greater emphasis on the genomic study of reproductive traits of males and females due to their economic importance. In this study, genome-wide associations were assessed for scrotal circumference at 210 d of age, scrotal circumference at 420 d of age, age at first calving, and age at second calving, in Canchim beef cattle. Data quality control was conducted resulting in 672,778 SNPs and 392 animals.Results: Associated SNPs were observed for scrotal circumference at 420 d of age(435 SNPs), followed by scrotal circumference at 210 d of age(12 SNPs), age at first calving(six SNPs), and age at second calving(four SNPs). We investigated whether significant SNPs were within genic or surrounding regions. Biological processes of genes were associated with immune system, multicellular organismal process, response to stimulus, apoptotic process, cellular component organization or biogenesis, biological adhesion, and reproduction.Conclusions: Few associations were observed for scrotal circumference at 210 d of age, age at first calving, and age at second calving, reinforcing their polygenic inheritance and the complexity of understanding the genetic architecture of reproductive traits. Finding many associations for scrotal circumference at 420 d of age in various regions of the Canchim genome also reveals the difficulty of targeting specific candidate genes that could act on fertility; nonetheless,the high linkage disequilibrium between loci herein estimated could aid to overcome this issue. Therefore, al relevant information about genomic regions influencing reproductive traits may contribute to target candidate genes for further investigation of causal mutations and aid in future genomic studies in Canchim cattle to improve the breeding program.     

基于单倍型肉牛屠宰性状全基因组关联分析研究

单倍型标记与数量性状基因座(quantitative trait loci，QTL)之间具有较强的连锁不平衡(linkage disequilibrium，LD)关系，在基因定位和因果突变鉴定方面具有较高的应用价值。为了评估单倍型标记在基因组研究中的作用，本研究在华西牛资源群体中，选取该群体于2008—2021年间屠宰的共计1 478头平均月龄为24个月的个体进行研究，其中公牛1 333头，母牛145头。利用770K高密度芯片数据，基于LD阈值(r²>0.3)及固定单核苷酸多态(single nucleotide polymorphism,SNP)个数(5个连续SNP)两种方法进行单倍型构建，分别采用单位点SNP标记和两种单倍型标记共3种标记，基于GCTA的混合线性模型(mixed linear model,MLM)，开展宰前活重(LW)和屠宰率(DP)等屠宰性状的全基因组关联分析(genome-wide association study，GWAS)，定位影响屠宰性状的显著(P<0.05) SNPs、单倍型块和候选基因，同时比较3种标记的GWAS结果，评估3种标记的优劣。结果显示，3种标记在全基因组范围内共找到16个的显著SNPs及单倍型区域，主要分布于1、5、6、14、16、17和28号染色体上，同时鉴定到FAM184B、PPM1K、LCORL、RIMS2等10个与屠宰性状相关的候选基因，其中，基于SNP标记方法鉴定到的3个候选基因，在利用基于单倍型标记的方法中也鉴定到，且单倍型鉴定到的显著性位点或区域大多位于基因内部。在两种单倍型构建方法中，与基于固定SNP个数构建单倍型进行GWAS相比，基于LD阈值的构建方法鉴定到了更多候选基因。本研究结果表明，以单倍型开展GWAS可以综合考虑SNP位点间连锁关系，能较好地揭示复杂性状的遗传结构。     

Pool‐based genome‐wide association study identified novel candidate regions on BTA9 and 14 for oleic acid percentage in Japanese Black cattle

Fatty acid composition is an important indicator of beef quality. The objective of this study was to search the potential candidate region for fatty acid composition. We performed pool‐based genome‐wide association studies (GWAS) for oleic acid percentage (C18:1) in a Japanese Black cattle population from the Hyogo prefecture. GWAS analysis revealed two novel candidate regions on BTA9 and BTA14. The most significant single nucleotide polymorphisms (SNPs) in each region were genotyped in a population (n = 899) to verify their effect on C18:1. Statistical analysis revealed that both SNPs were significantly associated with C18:1 (p = .0080 and .0003), validating the quantitative trait loci (QTLs) detected in GWAS. We subsequently selected VNN1 and LYPLA1 genes as candidate genes from each region on BTA9 and BTA14, respectively. We sequenced full‐length coding sequence (CDS) of these genes in eight individuals and identified a nonsynonymous SNP T66M on VNN1 gene as a putative candidate polymorphism. The polymorphism was also significantly associated with C18:1, but the p value (p = .0162) was higher than the most significant SNP on BTA9, suggesting that it would not be responsible for the QTL. Although further investigation will be needed to determine the responsible gene and polymorphism, our findings would contribute to development of selective markers for fatty acid composition in the Japanese Black cattle of Hyogo.     

Refined mapping of twinning-rate quantitative trait loci on bovine chromosome 5 and analysis of insulin-like growth factor-1 as a positional candidate gene

Twinning in cattle is a complex trait that is associated with economic loss and health issues such as abortion, dystocia, and reduced calf survival. Twinning-rate QTL have been detected previously on BTA5 in the North American Holstein and Norwegian dairy cattle populations and in a USDA herd selected for high twinning rate. In previous work with the North American Holstein population, the strongest evidence for a QTL was obtained from analysis of an extended, multiple-generation family. Using additional animals, an increased density of SNP marker association tests, and a combined linkage and linkage disequilibrium mapping method, we refined the position of this QTL in the North American Holstein population. Two sets of twinning-rate predicted transmitting abilities estimated during 2 different time periods in the North American dairy cattle population were used to provide validation of results. A total of 106 SNP and 3 microsatellites were used to scan the genomic region between 5 and 80 Mb on BTA5. Combined linkage-linkage disequilibrium analysis identified significant evidence for QTL within the 25- to 35-Mb and 64- to 70-Mb regions of BTA5. The IGF-1 gene (IGF1) was examined as a positional candidate gene and an SNP in intron 2 of IGF1 was significantly associated with twinning rate by using both data sets (P = 0.003 and P = 1.05 x 10(-6)). Replication of this association in other cattle populations will be required to examine the extent of linkage disequilibrium with the underlying quantitative trait nucleotide across breeds.     

基于SNP芯片的海南猪全基因组选择信号分析

旨在通过检测海南猪全基因组上的选择信号,以挖掘与海南猪重要经济性状相关的候选基因,并解析讨论海南猪在进化驯化历史中的受选择情况.本研究利用68头海南猪的GeneSeek Genomic Profiler Procine SNP 80K芯片数据,使用整合单倍型分数(integrated haplotype score,i...     

Haplotype phasing after joint estimation of recombination and linkage disequilibrium in breeding populations

A novel method for haplotype phasing in families after joint estimation of recombination fraction and linkage disequilibrium is developed. Results from Monte Carlo computer simulations show that the newly developed E.M. algorithm is accurate if true recombination fraction is 0 even for single families of relatively small sizes. Estimates of recombination fraction and linkage disequilibrium were 0.00 （SD 0.00） and 0.19 （SD 0.03） for simulated recombination fraction and linkage disequilibrium of 0.00 and 0.20, respectively. A genome fragmentation phasing strategy was developed and used for phasing haplotypes in a sire and 36 progeny using the 50 k Illumina BeadChip by： a） estimation of the recombination fraction and LD in consecutive SNPs using family information, b） linkage analyses between fragments, c） phasing of haplotypes in parents and progeny and in following generations. Homozygous SNPs in progeny allowed determination of paternal fragment inheritance, and deduction of SNP sequence information of haplotypes from dams. The strategy also allowed detection of genotyping errors. A total of 613 recombination events were detected after linkage analysis was carried out between fragments. Hot and cold spots were identified at the individual （sire level）. SNPs for which the sire and calf were heterozygotes became informative （over 90%） after the phasing of haplotypes. Average of regions of identity between half-sibs when comparing its maternal inherited haplotypes （with at least 20 SNP） in common was 0.11 with a maximum of 0.29 and a minimum of 0.05. A Monte-Carlo simulation of BTA1 with the same linkage disequilibrium structure and genetic linkage as the cattle family yielded a 99.98 and 99.94% of correct phases for informative SNPs in sire and calves, respectively.     

Estimation of genome-wide haplotype effects in half-sib designs

Genome-wide estimated breeding values can be computed from the simultaneous estimates of the effects of small intervals of DNA throughout the genome on a trait or traits of interest. Small intervals or segments of DNA can be created by the use of thousands of single nucleotide polymorphisms (SNP) available in panels of 10, 25 and 50 thousand SNP. A simulation study was conducted to compare factors that could influence the accuracy of genome-wide selection. Factors studied were the heritability of the trait, dispersion of quantitative trait loci (QTL) across the genome and size of the QTL effects. A 100-cM genome was assumed with 100 equally spaced SNP markers and 10 QTL. A granddaughter design was constructed with 20 sires and 100 sons per sire. Population-wide linkage disequilibrium was assumed to be sufficient after 25 generations of random mating starting with 30 sires and 400 dams. Best linear unbiased prediction was used to simultaneously estimate the effects of 99 SNP intervals, based on determining the SNP haplotype of each son inherited from the sire. Indicator variables were used in the model to indicate haplotype transmission. A genome-wide estimated breeding value was calculated as the sum of the appropriate haplotype interval estimates for each son. Correlations between estimated and true breeding values ranged from 0.60 to 0.79. Situations with unequally sized QTL effects and randomly dispersed QTL gave higher correlations. QTL positions could be estimated to within 2 cM or less.     

基于选择信号分析揭示猪终端父本群体间性状趋同的关键基因

【目的】试验旨在揭示终端父本皮特兰猪与杜洛克猪在人工选择作用下重要经济性状呈现出表型趋同的基因组变化特征。【方法】利用376头皮特兰猪、451头杜洛克猪品系Ⅰ、841头杜洛克猪品系Ⅱ和497头杜洛克猪品系Ⅲ群体的50K SNP芯片数据,以100 kb窗口、50 kb步长计算综合单倍型评分(iHS)和等位基因频率差(△AF),分别取前5%作为猪群体内、群体间的基因组选择信号候选区域;利用bedtools分别对iHS、△AF按照左右200 kb进行合并,每2个群体间合并后的iHS、△AF统计量的重叠区域定义为性状趋同区域,并挖掘该区域与猪重要经济性状相关的平行选择信号。【结果】iHS结果显示,在皮特兰猪和杜洛克猪4个群体内共检测到5 112个选择信号候选区域,总长约487.51 Mb。基于△AF方法,于皮特兰猪和杜洛克猪每2个群体间共检测到9 579个选择信号显著区域,总长约913.50 Mb。基于合并后的iHS和△AF,共检测到52个性状趋同区域,总长约4.67 Mb,注释到88个与猪的繁殖、胴体和肉质等性状相关的平行选择候选基因。【结论】皮特兰猪和杜洛克猪群体间存在性状趋同的基因组选择区域有52个,平行选择信号主要涉及猪的繁殖、胴体及肉质等重要经济性状,这与瘦肉型猪种相同的育种方向相关,这些关键基因的发现可为后续商业猪品种遗传改良提供参考。     

Confirmation of quantitative trait loci using a low-density single nucleotide polymorphism map for twinning and ovulation rate on bovine chromosome 5

Traditional genetic selection in cattle for traits with low heritability, such as reproduction, has had very little success. With the addition of DNA technologies to the genetic selection toolbox for livestock, the opportunity may exist to improve reproductive efficiency more rapidly in cattle. The US Meat Animal Research Center Production Efficiency Population has 9,186 twinning and 29,571 ovulation rate records for multiple generations of animals, but a significant number of these animals do not have tissue samples available for DNA genotyping. The objectives of this study were to confirm QTL for twinning and ovulation rate previously found on BTA5 and to evaluate the ability of GenoProb to predict genotypic information in a pedigree containing 16,035 animals when using genotypes for 24 SNP from 3 data sets containing 48, 724, or 2,900 animals. Marker data for 21 microsatellites on BTA5 with 297 to 3,395 animals per marker were used in conjunction with each data set of genotyped animals. Genotypic probabilities for females were used to calculate independent variables for regressions of additive, dominance, and imprinting effects. Genotypic regressions were fitted as fixed effects in a 2-trait mixed model analysis by using multiple-trait derivative-free REML. Each SNP was analyzed individually, followed by backward selection fitting all individually significant SNP simultaneously and then removing the least significant SNP until only significant SNP were left. Five significant SNP associations were detected for twinning rate and 3 were detected for ovulation rate. Two of these SNP, 1 for each trait, were significant for imprinting. Additional modeling of paternal and maternal allelic effects confirmed the initial results of imprinting done by contrasting heterozygotes. These results are supported by comparative mapping of mouse and human imprinted genes to this region of bovine chromosome 5.     

Validation of commercial DNA tests for quantitative beef quality traits

Associations between 3 commercially available genetic marker panels (GeneSTAR Quality Grade, GeneSTAR Tenderness, and Igenity Tender-GENE) and quantitative beef traits were validated by the US National Beef Cattle Evaluation Consortium. Validation was interpreted to be the independent confirmation of the associations between genetic tests and phenotypes, as claimed by the commercial genotyping companies. Validation of the quality grade test (GeneSTAR Quality Grade) was carried out on 400 Charolais x Angus crossbred cattle, and validation of the tenderness tests (GeneSTAR Tenderness and Igenity Tender-GENE) was carried out on over 1,000 Bos taurus and Bos indicus cattle. The GeneSTAR Quality Grade marker panel is composed of 2 markers (TG5, a SNP upstream from the start of the first exon of thyroglobulin, and QG2, an anonymous SNP) and is being marketed as a test associated with marbling and quality grade. In this validation study, the genotype results from this test were not associated with marbling score; however, the association of substituting favorable alleles of the marker panel with increased quality grade (percentage of cattle grading Choice or Prime) approached significance (P < or = 0.06), mainly due to the effect of 1 of the 2 markers. The GeneSTAR Tenderness and Igenity TenderGENE marker panels are being marketed as tests associated with meat tenderness, as assessed by Warner-Bratzler shear force. These marker panels share 2 common mu-calpain SNP, but each has a different calpastatin SNP. In both panels, there were highly significant (P < 0.001) associations of the calpastatin marker and the mu-calpain haplotype with tenderness. The genotypic effects of the 2 tenderness panels were similar to each other, with a 1 kg difference in Warner-Bratzler shear force being observed between the most and least tender genotypes. Unbiased and independent validation studies are important to help build confidence in marker technology and also as a potential source of data required to enable the integration of marker data into genetic evaluations. As DNA tests associated with more beef production traits enter the marketplace, it will become increasingly important, and likely more difficult, to find independent populations with suitable phenotypes for validation studies.     

Fine mapping of a calving QTL on Bos taurus autosome 18 in Holstein cattle

Decreased calving performance not only directly impacts the economic efficiency of dairy cattle farming but also influences public concern for animal welfare. Previous studies have revealed a QTL on Bos taurus autosome (BTA) 18 that has a large effect on calving traits in Holstein cattle. In this study, fine mapping of this QTL was performed using imputed high‐density SNP chip (HD) genotypes followed by imputed next‐generation sequencing (NGS) variants. BTA18 was scanned for seven direct calving traits in 6113 bulls with imputed HD genotypes. SNP rs136283363 (BTA18: 57 548 213) was consistently the most significantly associated SNP across all seven traits [e.g. p‐value = 2.04 × 10^?59 for birth index (BI)]. To finely map the QTL region and to explore pleiotropic effects, we studied NGS variants within the targeted region (BTA18: 57 321 450–57 625 355) for associations with direct calving traits and with three conformation traits. Significant variants were prioritized, and their biological relevance to the traits was interpreted. Considering their functional relationships with direct calving traits, SIGLEC12, CD33 and CEACAM18 were proposed as candidate genes. In addition, pleiotropic effects of this QTL region on direct calving traits and conformation traits were observed. However, the extent of linkage disequilibrium combined with the lack of complete annotation and potential errors in the Bos taurus genome assembly hampered our efforts to pinpoint the causal mutation.     

Assessing single-nucleotide polymorphism selection methods for the development of a low-density panel optimized for imputation in South African Drakensberger beef cattle

A major obstacle in applying genomic selection (GS) to uniquely adapted local breeds in less-developed countries has been the cost of genotyping at high densities of single-nucleotide polymorphisms (SNP). Cost reduction can be achieved by imputing genotypes from lower to higher densities. Locally adapted breeds tend to be admixed and exhibit a high degree of genomic heterogeneity thus necessitating the optimization of SNP selection for downstream imputation. The aim of this study was to quantify the achievable imputation accuracy for a sample of 1,135 South African (SA) Drakensberger cattle using several custom-derived lower-density panels varying in both SNP density and how the SNP were selected. From a pool of 120,608 genotyped SNP, subsets of SNP were chosen (1) at random, (2) with even genomic dispersion, (3) by maximizing the mean minor allele frequency (MAF), (4) using a combined score of MAF and linkage disequilibrium (LD), (5) using a partitioning-around-medoids (PAM) algorithm, and finally (6) using a hierarchical LD-based clustering algorithm. Imputation accuracy to higher density improved as SNP density increased; animal-wise imputation accuracy defined as the within-animal correlation between the imputed and actual alleles ranged from 0.625 to 0.990 when 2,500 randomly selected SNP were chosen vs. a range of 0.918 to 0.999 when 50,000 randomly selected SNP were used. At a panel density of 10,000 SNP, the mean (standard deviation) animal-wise allele concordance rate was 0.976 (0.018) vs. 0.982 (0.014) when the worst (i.e., random) as opposed to the best (i.e., combination of MAF and LD) SNP selection strategy was employed. A difference of 0.071 units was observed between the mean correlation-based accuracy of imputed SNP categorized as low (0.01 < MAF ≤ 0.1) vs. high MAF (0.4 < MAF ≤ 0.5). Greater mean imputation accuracy was achieved for SNP located on autosomal extremes when these regions were populated with more SNP. The presented results suggested that genotype imputation can be a practical cost-saving strategy for indigenous breeds such as the SA Drakensberger. Based on the results, a genotyping panel consisting of ~10,000 SNP selected based on a combination of MAF and LD would suffice in achieving a <3% imputation error rate for a breed characterized by genomic admixture on the condition that these SNP are selected based on breed-specific selection criteria.