Objective: The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods: Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler B...
Objective: The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods: Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler BeadChip. After applying the quality control of criteria of a call rate ${\geq}90%$ and minor allele frequency (MAF) ${\geq}0.01$, a total of 15,235 autosomal SNPs were left for genome-wide association (GWA) analysis. The GWA tests were performed using single-locus mixed linear model. Age at slaughter was fitted as fixed effect and sire included as a covariate. The level of genome-wide significance was set at $3.28{\times}10^{-6}$ (0.05/15,235), corresponding to Bonferroni correction for 15,235 multiple independent tests. Results: By employing EMMAX approach which is based on a mixed linear model and accounts for population stratification and relatedness, we identified 17 and 16 loci significantly (p<0.001) associated with carcass weight for the additive and dominant models, respectively. The second most significant (p = 0.000049) SNP (ARS-BFGL-NGS-28234) on bovine chromosome 4 (BTA4) at 21 Mb had an allele substitution effect of 43.45 kg. Some of the identified regions on BTA2, 6, 14, 22, and 24 were previously reported to be associated with quantitative trait loci for carcass weight in several beef cattle breeds. Conclusion: This is the first genome-wide association study using SNP chips on commercial Hanwoo steers, and some of the loci newly identified in this study may help to better DNA markers that determine increased beef production in commercial Hanwoo cattle. Further studies using a larger sample size will allow confirmation of the candidates identified in this study.
Objective: The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods: Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler BeadChip. After applying the quality control of criteria of a call rate ${\geq}90%$ and minor allele frequency (MAF) ${\geq}0.01$, a total of 15,235 autosomal SNPs were left for genome-wide association (GWA) analysis. The GWA tests were performed using single-locus mixed linear model. Age at slaughter was fitted as fixed effect and sire included as a covariate. The level of genome-wide significance was set at $3.28{\times}10^{-6}$ (0.05/15,235), corresponding to Bonferroni correction for 15,235 multiple independent tests. Results: By employing EMMAX approach which is based on a mixed linear model and accounts for population stratification and relatedness, we identified 17 and 16 loci significantly (p<0.001) associated with carcass weight for the additive and dominant models, respectively. The second most significant (p = 0.000049) SNP (ARS-BFGL-NGS-28234) on bovine chromosome 4 (BTA4) at 21 Mb had an allele substitution effect of 43.45 kg. Some of the identified regions on BTA2, 6, 14, 22, and 24 were previously reported to be associated with quantitative trait loci for carcass weight in several beef cattle breeds. Conclusion: This is the first genome-wide association study using SNP chips on commercial Hanwoo steers, and some of the loci newly identified in this study may help to better DNA markers that determine increased beef production in commercial Hanwoo cattle. Further studies using a larger sample size will allow confirmation of the candidates identified in this study.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
대상 데이터
com). Genes within the significant SNPs and their close vicinity were explored from National Center for Biotechnology Information database (http://www.ncbi.nlm.nih.gov/). We have further searched for the QTL regions overlap with the identified candidate regions from bovine QTL database (http://bovinegenome.
Nasal samples were collected using Performagene LIVESTOCK's nasal swab DNA collection kit (DNA Genotek Inc., Kanata, ON, Canada) from 220 Hanwoo steers from commercial Hanwoo production farms.
, Kanata, ON, Canada) from 220 Hanwoo steers from commercial Hanwoo production farms. The 220 animals were sired by 30 bulls ranging from 1 to 38 calves per sire. Carcass weight was measured at an average age of 31.
데이터처리
The general linear model (GLM) procedure of the Statistical Analysis (V.9.1, SAS Inc., Cary, NC, USA) was used to test for significant difference between the genotypes of the 17 SNPs that are significantly associated (p<0.001) with carcass weight.
7. Haplotype trend regression analysis was performed using SNP and Variation Suit v8.4.4 (Golden Helix, Inc., USA www.goldenhelix.com). Genes within the significant SNPs and their close vicinity were explored from National Center for Biotechnology Information database (http://www.
이론/모형
Genome-wide association (GWA) tests were performed using single-locus mixed linear model GWAS (EMMAX) using SNP and Variation Suit v8.5.0 (Golden Helix, Inc., USA www.goldenhelix.com). In GWAS, lack of accounting for population structure may lead to spurious association results [20].
성능/효과
After applying quality control by individuals, a total of 18,593 autosomal SNPs with an average spacing of 135.10 kb were filtered for a call rate ≥90% and minor allele frequency (MAF) ≥0.01.
For the additive model, the 17 significant SNPs (p<0.001) were distributed over 15 BTA containing 6 annotated genes, including LOC101903200, poly (ADP-ribose) polymerase family member 4 (PARP4), glycoprotein A33 (GPA33), NAD kinase (NADK), phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 (PREX2), and FERM domain containing 4B (FRMD4B).
We also filtered out SNPs that significantly deviated from Hardy-Weinberg equilibrium (HEW) with p<1×10–6. Subsequently, 3,223 SNPs that had MAF less than 0.01, 89 SNPs departed from the HWE and 121 SNPs with a call rate less than 90% (10% missing) were excluded from analysis. After applying the above quality control criteria, a total of 15,235 autosomal SNPs left for 220 Hanwoo steers were used for genome-wide association analysis.
45 kg (ARS-BFGLNGS- 28234). The most significant SNP (Hapmap60145-rs 29013637) had an allele substitution effect of 22.57 kg, whereas the second most significant SNP (ARS-BFGL-NGS-28234) had an effect of 43.45 kg (Table 1). It was notable that PREX2 and GPA33 genes were significant for both additive and dominant models.
To gain additional information on the loci that had a large effect on observed phenotypic variance, we further calculated the proportion of genetic variance explained by each SNP finding that the most significant SNP on BTA24 at 27.38 Mb explained 0.09% of the total variance, whereas the second most significant SNP accounted for about 0.08% of the total variance (Table 1). The proportion of variance explained by each significant SNP was very low showing that the polygenic nature of carcass weight is governed by many genes with small effects.
Twelve haplotype blocks distributed in 9 chromosomes were shown to have a significant (p<0.05) effect on carcass weight.
후속연구
, Lincoln, NE, USA) to identify loci that are significantly associated with carcass weight. The results of the current study will aid the development of selection tool in commercial Hanwoo cattle populations.
1 Mannen H Kohno M Nagata Y Independent mitochondrial origin and historical genetic differentiation in North Eastern Asian cattle Mol Phylogenet Evol 2004 32 539 44 15223036
5 Wythes J Shorthose W Dodt R Dickinson R Carcass and meat quality of Bos indicus × Bos taurus and Bos taurus cattle in northern Australia Aust J Exp Agric 1989 29 757 63
6 Zhang H Wang Z Wang S Li H Progress of genome wide association study in domestic animals J Anm Sci Biotechnol 2012 3 26
7 Stranger BE Stahl EA Raj T Progress and promise of genome-wide association studies for human complex trait genetics Genetics 2011 187 367 83 21115973
8 Cericola F Portis E Lanteri S Linkage disequilibrium and genome-wide association analysis for anthocyanin pigmentation and fruit color in eggplant BMC Genomics 2014 15 896 25311640
9 Nishimura S Watanabe T Mizoshita K Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle BMC Genet 2012 13 40 22607022
10 Setoguchi K Furuta M Hirano T Cross-breed comparisons identified a critical 591-kb region for bovine carcass weight QTL (CW-2) on chromosome 6 and the Ile-442–Met substitution in NCAPG as a positional candidate BMC Genet 2009 10 43 19653884
11 Lee SH Choi BH Lim D Genome-wide association study identifies major loci for carcass weight on BTA14 in Hanwoo (Korean cattle) PLOS ONE 2013 8 e74677 24116007
12 Lee SH van der Werf J Lee SH Genome wide QTL mapping to identify candidate genes for carcass traits in Hanwoo (Korean Cattle) Genes Genom 2012 34 43 9
13 Nishimura S Watanabe T Mizoshita K Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle BMC Genet 2012 13 40 22607022
14 Takasuga A Watanabe T Mizoguchi Y Identification of bovine QTL for growth and carcass traits in Japanese Black cattle by replication and identical-by-descent mapping Mamm Genome 2007 18 125 36 17347893
15 Sorbolini S Bongiorni S Cellesi M Genome wide association study on beef production traits in Marchigiana cattle breed J Anim Breed Genet 2017 134 43 8 27329851
16 Jiang Z Michal JJ Chen J Discovery of novel genetic networks associated with 19 economically important traits in beef cattle Int J Biol Sci 2009 5 528 42 19727437
18 Podisi BK Knott SA Burt DW Hocking PM Comparative analysis of quantitative trait loci for body weight, growth rate and growth curve parameters from 3 to 72 weeks of age in female chickens of a broiler–layer cross BMC Genet 2013 14 22 23496818
19 Middelbos IS Vester BM Karr-Lilienthal LK Schook LB Swanson KS Age and diet affect gene expression profile in canine skeletal muscle PLOS ONE 2009 4 e4481 19221602
20 Kang HM Sul JH Service SK Variance component model to account for sample structure in genome-wide association studies Nat Genet 2010 42 348 54 20208533
22 Fortes MR Reverter A Nagaraj SH A single nucleotide polymorphism-derived regulatory gene network underlying puberty in 2 tropical breeds of beef cattle J Anm Sci 2011 89 1669 83
23 Shannon P Markiel A Ozier O Cytoscape: a software environment for integrated models of biomolecular interaction networks Genome Res 2003 13 2498 504 14597658
24 Kim Y Ryu J Woo J Genome-wide association study reveals five nucleotide sequence variants for carcass traits in beef cattle Anim Genet 2011 42 361 5 21749418
25 Lee SH Choi BH Lim D Genome-wide association study identifies major loci for carcass weight on BTA14 in Hanwoo (Korean cattle) PLOS ONE 2013 8 e74677 24116007
26 Espigolan R Baldi F Boligon AA Associations between single nucleotide polymorphisms and carcass traits in Nellore cattle using high-density panels Genet Mol Res 2015 14 11133 44 26400344
27 Rempel LA Casas E Shackelford SD Wheeler TL Relationship of polymorphisms within metabolic genes and carcass traits in crossbred beef cattle J Anim Sci 2012 90 1311 6 22100592
28 Utsunomiya YT do Carmo AS Carvalheiro R Genome-wide association study for birth weight in Nellore cattle points to previously described orthologous genes affecting human and bovine height BMC Genet 2013 14 52 23758625
29 McClure MC Morsci NS Schnabel RD A genome scan for quantitative trait loci influencing carcass, post-natal growth and reproductive traits in commercial Angus cattle Anim Genet 2010 41 597 607 20477797
30 Ikenouchi J Umeda M FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex Proc Natl Acad Sci USA 2010 107 748 53 20080746
31 Kim JJ Farnir F Savell J Taylor JF Detection of quantitative trait loci for growth and beef carcass fatness traits in a cross between Bos taurus (Angus) and Bos indicus (Brahman) cattle J Anim Sci 2003 8 1933 42
32 Rouleau M Patel A Hendzel MJ PARP inhibition: PARP1 and beyond Nat Rev Cancer 2010 10 293 301 20200537
34 Casas E Shackelford SD Keele JW Quantitative trait loci affecting growth and carcass composition of cattle segregating alternate forms of myostatin J Anim Sci 2000 78 560 9 10764062
35 Kneeland J Li C Basarab J Snelling W Identification and fine mapping of quantitative trait loci for growth traits on bovine chromosomes 2, 6, 14, 19, 21, and 23 within one commercial line of Bos taurus J Anim Sci 2004 82 3405 14 15537758
36 Kim JW Park SI Yeo JS Linkage mapping and QTL on chromosome 6 in Hanwoo (Korean cattle) Asian-Australas J Anim Sci 2003 16 1402 5
37 Daly MJ Rioux JD Schaffner SF Hudson TJ Lander ES High-resolution haplotype structure in the human genome Nat Genet 2001 29 229 32 11586305
38 Lemos MVA Chiaia HLJ Berton MP Genome-wide association between single nucleotide polymorphisms with beef fatty acid profile in Nellore cattle using the single step procedure BMC Genomics 2016 17 213 26960694
39 Puig-Oliveras A Ballester M Corominas J A co-association network analysis of the genetic determination of pig conformation, growth and fatness PLOS ONE 2014 9 e114862 25503799
41 Laumet G Petitprez V Sillaire A A study of the association between the ADAM12 and SH3PXD2A (SH3MD1) genes and Alzheimer's disease Neurosci Lett 2010 468 1 2 19837132
44 Coles CA Wadeson J Leyton CP Proliferation rates of bovine primary muscle cells relate to liveweight and carcase weight in cattle PLOS ONE 2015 10 e0124468 25875203
45 Cieslak D Kuryl J Kapelanski W Relationship between genotypes at at MYOG, MYF3 and MYF5 loci and carcass meat and fat deposition traits in pigs Animal Science Papers and Reports (Poland) 2002
46 Brunelli S Relaix F Baesso S Buckingham M Cossu G Beta catenin-independent activation of MyoD in presomitic mesoderm requires PKC and depends on Pax3 transcriptional activity Dev Biol 2007 304 604 14 17275805
47 Te Pas M Harders F Soumillion A Genetic variation at the porcine MYF-5 gene locus. Lack of association with meat production traits Mamm Genome 1999 10 123 7 9922391
48 Stahl EA Raychaudhuri S Remmers EF Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci Nat Genet 2010 42 508 14 20453842
49 Clayton DG Walker NM Smyth DJ Population structure, differential bias and genomic control in a large-scale, case-control association study Nat Genet 2005 37 1243 6 16228001
※ AI-Helper는 부적절한 답변을 할 수 있습니다.