Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle.
ABSTRACT: Improving the genetic process of growth traits is one of the major goals in the beef cattle industry, as it can increase meat production and reduce the cost of raising animals. Although several quantitative trait loci affecting growth traits in beef cattle have been identified, the genetic architecture of these economically important traits remains elusive. This study aims to map single nucleotide polymorphisms (SNPs) and genes associated with birth weight (BW), yearling weight (YW), average daily gain from birth to yearling (BYADG), and body weight at the age of 18 months (18MW) in a Chinese Simmental beef cattle population using a weighted, single-step, genome-wide association study (wssGWAS). Phenotypic and pedigree data from 6022 animals and genotypes from 744 animals (596,297 SNPs) were used for an association analysis. The results showed that 66 genomic windows explained 1.01-20.15% of the genetic variance for the four examined traits, together with the genes near the top SNP within each window. Furthermore, the identified genomic windows (>1%) explained 50.56%, 57.71%, 61.78%, and 37.82% of the genetic variances for BW, YW, BYADG, and 18MW, respectively. Genes with potential functions in muscle development and regulation of cell growth were highlighted as candidates for growth traits in Simmental cattle (SQOR and TBCB for BW, MYH10 for YW, RLF for BYADG, and ARHGAP31 for 18MW). Moreover, we found 40 SNPs that had not previously been identified as being associated with growth traits in cattle. These findings will further advance our understanding of the genetic basis for growth traits and will be useful for the molecular breeding of BW, YW, BYADG, and 18MW in the context of genomic selection in beef cattle.
Project description:Data on calving ease (CE) and birth, weaning weight (WW), and yearling weight (YW) were obtained from the American Simmental Association (ASA) and included pedigree and performance information on 11,640,735 animals. Our objective was to quantify differential response from selection for high CE vs. low birth weight (LBW) in first-calf Simmental heifers. We hypothesized that direct selection for CE should be used as the primary approach to reduce dystocia and mitigate losses in growth-related traits. WW and YW were adjusted to 205 and 365 d of age, respectively. Sire and maternal grandsire (co)variance components for CE, birth weight (BW), and 205-d weaning weight (205-d WW), and sire covariance components for 160-d postweaning gain (160-d gain) were estimated using a sire-maternal grandsire model. Direct and maternal expected progeny differences (EPD) for CE, BW, and 205-d WW and direct EPD for 160-d gain and 365-d yearling weight (365-d YW) for first-calf Simmental heifers population (465,710 animals) were estimated using a threshold-linear multivariate maternal animal model. This population was used to estimate genetic trends and as a selection pool (control) for various selection scenarios. Selection scenarios were high CE (HCE), LBW, the all-purpose selection index (API = -1.8 BW + 1.3 CE + 0.10 WW + 0.20 YW) of the ASA and its two derived subindices: (API1 = 1.3 CE + 0.20 YW) and (API2 = -1.8 BW + 0.20 YW), and lastly Dickerson's selection index (DSI = -3.2 BW + YW). Data for each selection scenario were created by selecting sires with EPD greater than or equal to the average along with the top 75% of dams. Comparison between selection scenarios involved evaluating the direct and maternal genetic trends from these scenarios. Direct heritabilities for CE, BW, 205-d WW, 160-d gain, and 365-d YW of Simmental cattle were 0.23, 0.52, 0.28, 0.21, and 0.33, respectively. The single trait, HCE, selection scenario, as opposed to LBW, increased the intercept for CE by 57.7% and the slopes (P < 0.001) for BW, 205-d WW, 160-d gain, and 365-d YW by 27.9%, 37.5%, 16%, and 28%, respectively. Comparisons of various selection scenarios revealed that the CE-based selection scenarios (HCE, API, and API1) had a greater response for CE and growth traits.
Project description:<h4>Background</h4>Single nucleotide polymorphism (SNP) arrays have facilitated discovery of genetic markers associated with complex traits in domestic cattle; thereby enabling modern breeding and selection programs. Genome-wide association analyses (GWAA) for growth traits were conducted on 10,837 geographically diverse U.S. Gelbvieh cattle using a union set of 856,527 imputed SNPs. Birth weight (BW), weaning weight (WW), and yearling weight (YW) were analyzed using GEMMA and EMMAX (via imputed genotypes). Genotype-by-environment (GxE) interactions were also investigated.<h4>Results</h4>GEMMA and EMMAX produced moderate marker-based heritability estimates that were similar for BW (0.36-0.37, SE?=?0.02-0.06), WW (0.27-0.29, SE?=?0.01), and YW (0.39-0.41, SE?=?0.01-0.02). GWAA using 856K imputed SNPs (GEMMA; EMMAX) revealed common positional candidate genes underlying pleiotropic QTL for Gelbvieh growth traits on BTA6, BTA7, BTA14, and BTA20. The estimated proportion of phenotypic variance explained (PVE) by the lead SNP defining these QTL (EMMAX) was larger and most similar for BW and YW, and smaller for WW. Collectively, GWAAs (GEMMA; EMMAX) produced a highly concordant set of BW, WW, and YW QTL that met a nominal significance level (P???1e-05), with prioritization of common positional candidate genes; including genes previously associated with stature, feed efficiency, and growth traits (i.e., PLAG1, NCAPG, LCORL, ARRDC3, STC2). Genotype-by-environment QTL were not consistent among traits at the nominal significance threshold (P???1e-05); although some shared QTL were apparent at less stringent significance thresholds (i.e., P???2e-05).<h4>Conclusions</h4>Pleiotropic QTL for growth traits were detected on BTA6, BTA7, BTA14, and BTA20 for U.S. Gelbvieh beef cattle. Seven QTL detected for Gelbvieh growth traits were also recently detected for feed efficiency and growth traits in U.S. Angus, SimAngus, and Hereford cattle. Marker-based heritability estimates and the detection of pleiotropic QTL segregating in multiple breeds support the implementation of multiple-breed genomic selection.
Project description:In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight.
Project description:Hanwoo, an important indigenous and popular breed of beef cattle in Korea, shows rapid growth and has high meat quality. Its yearling weight (YW) and carcass traits (backfat thickness, carcass weight- CW, eye muscle area, and marbling score) are economically important for selection of young and proven bulls. However, measuring carcass traits is difficult and expensive, and can only be performed postmortem. Genomic selection has become an appealing procedure for genetic evaluation of these traits (by inclusion of the genomic data) along with the possibility of multi-trait analysis. The aim of this study was to compare conventional best linear unbiased prediction (BLUP) and single-step genomic BLUP (ssGBLUP) methods, using both single-trait (ST-BLUP, ST-ssGBLUP) and multi-trait (MT-BLUP, MT-ssGBLUP) models to investigate the improvement of breeding-value accuracy for carcass traits and YW. The data comprised of 15,279 phenotypic records for YW and 5,824 records for carcass traits, and 1,541 genotyped animals for 34,479 single-nucleotide polymorphisms. Accuracy for each trait and model was estimated only for genotyped animals by five-fold cross-validation. ssGBLUP models (ST-ssGBLUP and MT-ssGBLUP) showed ~19% and ~36% greater accuracy than conventional BLUP models (ST-BLUP and MT-BLUP) for YW and carcass traits, respectively. Within ssGBLUP models, the accuracy of the genomically estimated breeding value for CW increased (19%) when ST-ssGBLUP was replaced with the MT-ssGBLUP model, as the inclusion of YW in the analysis led to a strong genetic correlation with CW (0.76). For backfat thickness, eye muscle area, and marbling score, ST- and MT-ssGBLUP models yielded similar accuracy. Thus, combining pedigree and genomic data via the ssGBLUP model may be a promising way to ensure acceptable accuracy of predictions, especially among young animals, for ongoing Hanwoo cattle breeding programs. MT-ssGBLUP is highly recommended when phenotypic records are limited for one of the two highly correlated genetic traits.
Project description:The weighted single-step genomic best linear unbiased prediction (GBLUP) method has been proposed to exploit information from genotyped and non-genotyped relatives, allowing the use of weights for single-nucleotide polymorphism in the construction of the genomic relationship matrix. The purpose of this study was to investigate the accuracy of genetic prediction using the following single-trait best linear unbiased prediction methods in Hanwoo beef cattle: pedigree-based (PBLUP), un-weighted (ssGBLUP), and weighted (WssGBLUP) single-step genomic methods. We also assessed the impact of alternative single and window weighting methods according to their effects on the traits of interest. The data was comprised of 15,796 phenotypic records for yearling weight (YW) and 5622 records for carcass traits (backfat thickness: BFT, carcass weight: CW, eye muscle area: EMA, and marbling score: MS). Also, the genotypic data included 6616 animals for YW and 5134 for carcass traits on the 43,950 single-nucleotide polymorphisms. The ssGBLUP showed significant improvement in genomic prediction accuracy for carcass traits (71%) and yearling weight (99%) compared to the pedigree-based method. The window weighting procedures performed better than single SNP weighting for CW (11%), EMA (11%), MS (3%), and YW (6%), whereas no gain in accuracy was observed for BFT. Besides, the improvement in accuracy between window WssGBLUP and the un-weighted method was low for BFT and MS, while for CW, EMA, and YW resulted in a gain of 22%, 15%, and 20%, respectively, which indicates the presence of relevant quantitative trait loci for these traits. These findings indicate that WssGBLUP is an appropriate method for traits with a large quantitative trait loci effect.
Project description:<b>Objective:</b> Body weight is an important economic trait for a goat, which greatly affects animal growth and survival. The purpose of this study was to identify genes associated with birth weight (BW), weaning weight (WW), and yearling weight (YW). <b>Materials and Methods:</b> In this study, a genome-wide association study (GWAS) of BW, WW, and YW was determined using the GGP_Goat_70K single-nucleotide polymorphism (SNP) chip in 1,920 Inner Mongolia cashmere goats. <b>Results:</b> We discovered that 21 SNPs were significantly associated with BW on the genome-wide levels. These SNPs were located in 10 genes, e.g., Mitogen-Activated Protein Kinase 3 (<i>MAPK3</i>), LIM domain binding 2 (<i>LDB2</i>), and low-density lipoprotein receptor-related protein 1B (<i>LRP1B</i>), which may be related to muscle growth and development in Inner Mongolia Cashmere goats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these genes were significantly enriched in the regulation of actin cytoskeleton and phospholipase D signaling pathway etc. <b>Conclusion:</b> In summary, this study will improve the marker-assisted breeding of Inner Mongolia cashmere goats and the molecular mechanisms of important economic traits.
Project description:Body weight (BW) is an important longitudinal trait that directly described the growth gain of bovine in production. However, previous genome-wide association study (GWAS) mainly focused on the single-record traits, with less attention paid to longitudinal traits. Compared with traditional GWAS models, the association studies based on the random regression model (GWAS-RRM) have better performance in the control of the false positive rate through considering time-stage effects. In this study, the BW trait data were collected from 808 Chinese Simmental beef cattle aged 0, 6, 12, and 18 months, then we performed a GWAS-RRM to fit the time-varied SNP effect. The results showed a total of 37 significant SNPs were associated with BW. Gene functional annotation and enrichment analysis indicated <i>FGF4</i>, <i>ANGPT4</i>, <i>PLA2G4A</i>, and <i>ITGA5</i> were promising candidate genes for BW. Moreover, these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. These findings will provide prior molecular information for bovine gene-based selection, as well as facilitate the extensive application of GWAS-RRM in domestic animals.
Project description:Carcass traits of beef cattle have been genetically improved to increase yield of high quality meat. Genome-wide association study (GWAS) is a powerful method to identify genetic variants associated with carcass traits. For the 770K genotyped SNPs from 1141 Chinese Simmental cattle, we used the compressed mixed linear model (CMLM) to perform a genome-wide association study for knuckle, biceps and shank of beef carcass traits. Seventeen significantly associated SNPs were found, which are located on BTA6, BTA14 and BTA15. Interestingly, one pleiotropic quantitative trait nucleotide (QTN), named BovineHD1400007259 (p < 10-8) within the well-known gene region PLAG1-CHCHD7 on BTA14, was found to govern variation of the knuckle, biceps and shank traits. The QTN accounted for 8.6% of phenotypic variance for biceps. In addition, 16 more SNPs distributed on BTA14 were detected as being associated with the carcass traits.
Project description:BACKGROUND:Average daily gain (ADG) is an important trait that contributes to the production efficiency and economic benefits in the beef cattle industry. The molecular mechanisms of ADG have not yet been fully explored because most recent association studies for ADG are based on SNPs or haplotypes. We reported a systematic CNV discovery and association analysis for ADG in Chinese Simmental beef cattle. RESULTS:Our study identified 4912 nonredundant CNVRs with a total length of ~?248.7?Mb, corresponding to ~?8.9% of the cattle genome. Using probe-based CNV association, we identified 24 and 12 significant SNP probes within five deletions and two duplications for ADG, respectively. Among them, we found one common deletion with 89?kb imbedded in LHFPL Tetraspan Subfamily Member 6 (LHFPL6) at 22.9?Mb on BTA12, which has high frequency (12.9%) dispersing across population. CNV selection test using VST statistic suggested this common deletion may be under positive selection in Chinese Simmental cattle. Moreover, this deletion was not overlapped with any candidate SNP for ADG compared with previous SNPs-based association studies, suggesting its important role for ADG. In addition, we identified one rare deletion near gene Growth Factor Receptor-bound Protein 10 (GRB10) at 5.1?Mb on BTA4 for ADG using both probe-based association and region-based approaches. CONCLUSIONS:Our results provided some valuable insights to elucidate the genetic basis of ADG in beef cattle, and these findings offer an alternative perspective to understand the genetic mechanism of complex traits in terms of copy number variations in farm animals.
Project description:Studies are being conducted on the applicability of genomic data to improve the accuracy of the selection process in livestock, and genome-wide association studies (GWAS) provide valuable information to enhance the understanding on the genetics of complex traits. The aim of this study was to identify genomic regions and genes that play roles in birth weight (BW), weaning weight adjusted for 210 days of age (WW), and long-yearling weight adjusted for 420 days of age (LYW) in Canchim cattle. GWAS were performed by means of the Generalized Quasi-Likelihood Score (GQLS) method using genotypes from the BovineHD BeadChip and estimated breeding values for BW, WW, and LYW. Data consisted of 285 animals from the Canchim breed and 114 from the MA genetic group (derived from crossings between Charolais sires and ½ Canchim + ½ Zebu dams). After applying a false discovery rate correction at a 10% significance level, a total of 4, 12, and 10 SNPs were significantly associated with BW, WW, and LYW, respectively. These SNPs were surveyed to their corresponding genes or to surrounding genes within a distance of 250 kb. The genes DPP6 (dipeptidyl-peptidase 6) and CLEC3B (C-type lectin domain family 3 member B) were highlighted, considering its functions on the development of the brain and skeletal system, respectively. The GQLS method identified regions on chromosome associated with birth weight, weaning weight, and long-yearling weight in Canchim and MA animals. New candidate regions for body weight traits were detected and some of them have interesting biological functions, of which most have not been previously reported. The observation of QTL reports for body weight traits, covering areas surrounding the genes (SNPs) herein identified provides more evidence for these associations. Future studies targeting these areas could provide further knowledge to uncover the genetic architecture underlying growth traits in Canchim cattle.