Genome Wide Association Studies for Milk Production Traits in Chinese Holstein Population

Genome-wide association studies (GWAS) based on high throughput SNP genotyping technologies open a broad avenue for exploring genes associated with milk production traits in dairy cattle. Motivated by pinpointing novel quantitative trait nucleotide (QTN) across Bos Taurus genome, the present study is to perform GWAS to identify genes affecting milk production traits using current state-of-the-art SNP genotyping technology, i.e., the Illumina BovineSNP50 BeadChip. In the analyses, the five most commonly evaluated milk production traits are involved, including milk yield (MY), milk fat yield (FY), milk protein yield (PY), milk fat percentage (FP) and milk protein percentage (PP). Estimated breeding values (EBVs) of 2,093 daughters from 14 paternal half-sib families are considered as phenotypes within the framework of a daughter design. Association tests between each trait and the 54K SNPs are achieved via two different analysis approaches, a paternal transmission disequilibrium test (TDT)-based approach (L1-TDT) and a mixed model based regression analysis (MMRA). In total, 105 SNPs were detected to be significantly associated genome-wise with one or multiple milk production traits. Of the 105 SNPs, 38 were commonly detected by both methods, while four and 63 were solely detected by L1-TDT and MMRA, respectively. The majority (86 out of 105) of the significant SNPs is located within the reported QTL regions and some are within or close to the reported candidate genes. In particular, two SNPs, ARS-BFGL-NGS-4939 and BFGL-NGS-118998, are located close to the DGAT1 gene (160bp apart) and within the GHR gene, respectively. Our findings herein not only provide confirmatory evidences for previously findings, but also explore a suite of novel SNPs associated with milk production traits, and thus form a solid basis for eventually unraveling the causal mutations for milk production traits in dairy cattle.

[1]  M. Georges,et al.  Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing. , 1995, Genetics.

[2]  W. Ewens,et al.  The transmission/disequilibrium test: history, subdivision, and admixture. , 1995, American journal of human genetics.

[3]  D B Allison,et al.  Multiple phenotype modeling in gene-mapping studies of quantitative traits: power advantages. , 1998, American journal of human genetics.

[4]  M. Georges,et al.  A QTL with major effect on milk yield and composition maps to bovine Chromosome 14 , 1998, Mammalian Genome.

[5]  P. VanRaden,et al.  A genome scan for QTL influencing milk production and health traits in dairy cattle. , 1999, Physiological genomics.

[6]  J. Woolliams,et al.  Testing for the presence of previously identified QTL for milk production traits in new populations. , 2000, Animal genetics.

[7]  L R Schaeffer,et al.  Experience with a test-day model. , 2000, Journal of dairy science.

[8]  G. Brockmann,et al.  A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14 , 2001, Mammalian Genome.

[9]  J C Whittaker,et al.  Mapping quantitative trait Loci using generalized estimating equations. , 2001, Genetics.

[10]  M. Goddard,et al.  Prediction of identity by descent probabilities from marker-haplotypes , 2001, Genetics Selection Evolution.

[11]  R. Reents,et al.  Comparison of estimated breeding values, daughter yield deviations and de-regressed proofs within a whole genome scan for QTL , 2001 .

[12]  R C Elston,et al.  Transmission/disequilibrium tests for quantitative traits , 2001, Genetic epidemiology.

[13]  C. V. Van Tassell,et al.  A genome scan to identify quantitative trait loci affecting economically important traits in a US Holstein population. , 2001, Journal of dairy science.

[14]  H. Lewin,et al.  Detection of quantitative trait loci influencing dairy traits using a model for longitudinal data. , 2002, Journal of dairy science.

[15]  M. Mni,et al.  Simultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14. , 2002, Genetics.

[16]  C. Weinberg,et al.  Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. , 2002, American journal of epidemiology.

[17]  A. W. Kuss,et al.  Associations of a polymorphic AP-2 binding site in the 5'-flanking region of the bovine beta-lactoglobulin gene with milk proteins. , 2003, Journal of dairy science.

[18]  J. Williams,et al.  Mapping and SNP analysis of bovine candidate genes for meat and carcass quality. , 2003, Animal genetics.

[19]  A. Malafosse,et al.  Combined analysis of data from two granddaughter designs: A simple strategy for QTL confirmation and increasing experimental power in dairy cattle , 2003, Genetics Selection Evolution.

[20]  Didier Boichard,et al.  Detection of genes influencing economic traits in three French dairy cattle breeds , 2003, Genetics Selection Evolution.

[21]  Michel Georges,et al.  Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition. , 2002, Genetics.

[22]  Jian Huang,et al.  Genetic linkage analysis of a dichotomous trait incorporating a tightly linked quantitative trait in affected sib pairs. , 2003, American journal of human genetics.

[23]  D. de Koning,et al.  Quantitative trait loci affecting milk production traits in Finnish Ayrshire dairy cattle. , 2003, Journal of dairy science.

[24]  P M VanRaden,et al.  Detection of quantitative trait loci affecting milk production, health, and reproductive traits in Holstein cattle. , 2004, Journal of dairy science.

[25]  Leif Andersson,et al.  Domestic-animal genomics: deciphering the genetics of complex traits , 2004, Nature Reviews Genetics.

[26]  R. Fernando,et al.  Comparing Linkage Disequilibrium-Based Methods for Fine Mapping Quantitative Trait Loci , 2004, Genetics.

[27]  Michel Georges,et al.  Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  H. Thomsen,et al.  The DGAT1 K232A mutation is not solely responsible for the milk production quantitative trait locus on the bovine chromosome 14. , 2004, Journal of dairy science.

[29]  R. Christenson,et al.  Allelic variation in the secreted folate binding protein gene is associated with uterine capacity in swine. , 2005, Journal of animal science.

[30]  M. Daly,et al.  Genome-wide association studies for common diseases and complex traits , 2005, Nature Reviews Genetics.

[31]  S. Heath,et al.  Single-nucleotide polymorphism versus microsatellite markers in a combined linkage and segregation analysis of a quantitative trait , 2005, BMC Genetics.

[32]  D. Duggan,et al.  Recent developments in genomewide association scans: a workshop summary and review. , 2005, American journal of human genetics.

[33]  J. Weller,et al.  Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle. , 2005, Genome research.

[34]  R. Christenson,et al.  Allelic variation in the erythropoietin receptor gene is associated with uterine capacity and litter size in swine. , 2005, Animal genetics.

[35]  S. Kamiński,et al.  Nucleotide sequence polymorphism within exon 4 of the bovine prolactin gene and its associations with milk performance traits. , 2005, Journal of applied genetics.

[36]  David W Craig,et al.  Applications of whole-genome high-density SNP genotyping , 2005, Expert review of molecular diagnostics.

[37]  J. Noguera,et al.  Polymorphism of the pig 2,4-dienoyl CoA reductase 1 gene (DECR1) and its association with carcass and meat quality traits. , 2005, Journal of animal science.

[38]  H. Thomsen,et al.  Mapping of quantitative trait loci for lactation persistency traits in German Holstein dairy cattle. , 2006, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[39]  M. Georges,et al.  The Role of the Bovine Growth Hormone Receptor and Prolactin Receptor Genes in Milk, Fat and Protein Production in Finnish Ayrshire Dairy Cattle , 2006, Genetics.

[40]  G. Jansen,et al.  Transmission disequilibrium test for quantitative trait loci detection in livestock populations. , 2006, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[41]  The choice of phenotypes for use of marker assisted selection in dairy cattle. , 2006 .

[42]  M. Lund,et al.  Quantitative trait loci for fertility traits in Finnish Ayrshire cattle , 2008, Genetics Selection Evolution.

[43]  M. Lund,et al.  Detection and modelling of time-dependent QTL in animal populations , 2008, Genetics Selection Evolution.

[44]  R. Fernando,et al.  Power and Precision of Alternate Methods for Linkage Disequilibrium Mapping of Quantitative Trait Loci , 2007, Genetics.

[45]  M. Georges Mapping, fine mapping, and molecular dissection of quantitative trait Loci in domestic animals. , 2007, Annual review of genomics and human genetics.

[46]  H. Deng,et al.  Bayesian mapping of quantitative trait loci for multiple complex traits with the use of variance components. , 2007, American journal of human genetics.

[47]  G. Abecasis,et al.  A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants , 2007, Science.

[48]  Rebecca F. Halperin,et al.  A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. , 2007, The Journal of clinical psychiatry.

[49]  G. Erhardt,et al.  Joint analysis of the influence of CYP11B1 and DGAT1 genetic variation on milk production, somatic cell score, conformation, reproduction, and productive lifespan in German Holstein cattle. , 2007, Journal of animal science.

[50]  C Maltecca,et al.  Quantitative trait loci affecting milk yield and protein percentage in a three-country Brown Swiss population. , 2008, Journal of dairy science.

[51]  P. Horin,et al.  Single nucleotide polymorphisms of interleukin-1 beta related genes and their associations with infection in the horse. , 2008, Developments in biologicals.

[52]  T. Manolio,et al.  How to Interpret a Genome-wide Association Study Topic Collections , 2022 .

[53]  F. Schenkel,et al.  A genome scan to detect quantitative trait loci for economically important traits in Holstein cattle using two methods and a dense single nucleotide polymorphism map. , 2008, Journal of dairy science.

[54]  B. Guldbrandtsen,et al.  Detection of quantitative trait loci in Danish Holstein cattle affecting clinical mastitis, somatic cell score, udder conformation traits, and assessment of associated effects on milk yield. , 2008, Journal of dairy science.

[55]  H. Help,et al.  SNiPORK – A Microarray of SNPs in Candidate Genes Potentially Associated with Pork Yield and Quality – Development and Validation in Commercial Breeds , 2008, Animal biotechnology.

[56]  P. Visscher,et al.  Family-based genome-wide association studies. , 2009, Pharmacogenomics.

[57]  Yusuke Nakamura,et al.  A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma , 2009, Journal of Human Genetics.

[58]  Bayesian shrinkage mapping for multiple QTL in half-sib families , 2009, Heredity.

[59]  M. Goddard,et al.  Mapping genes for complex traits in domestic animals and their use in breeding programmes , 2009, Nature Reviews Genetics.

[60]  K. Williams,et al.  Some things just have to be done in vivo: GPIHBP1, caloric delivery, and the generation of remnant lipoproteins. , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[61]  Timothy P. L. Smith,et al.  Development and Characterization of a High Density SNP Genotyping Assay for Cattle , 2009, PloS one.

[62]  Yan Guo,et al.  Powerful Bivariate Genome-Wide Association Analyses Suggest the SOX6 Gene Influencing Both Obesity and Osteoporosis Phenotypes in Males , 2009, PloS one.

[63]  A. Prasad,et al.  A whole genome scan to map QTL for milk production traits and somatic cell score in Canadian Holstein bulls. , 2009, Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie.

[64]  T. Kunej,et al.  Database of cattle candidate genes and genetic markers for milk production and mastitis , 2009, Animal genetics.

[65]  H. Deng,et al.  Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equations , 2009, Genetic epidemiology.

[66]  I. Russ,et al.  Confirmation and refinement of a QTL on BTA5 affecting milk production traits in the Fleckvieh dual purpose cattle breed. , 2010, Animal genetics.

[67]  Frank Dudbridge,et al.  Family-based association studies. , 2011, Methods in molecular biology.