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Genome-wide association study of porcine hematological parameters in a Large White × Minzhu F2 resource population.

ABSTRACT: Hematological traits, which are important indicators of immune function in animals, have been commonly examined as biomarkers of disease and disease severity in humans and animals. Genome-wide significant quantitative trait loci (QTLs) provide important information for use in breeding programs of animals such as pigs. QTLs for hematological parameters (hematological traits) have been detected in pig chromosomes, although these are often mapped by linkage analysis to large intervals making identification of the underlying mutation problematic. Single nucleotide polymorphisms (SNPs) are the common form of genetic variation among individuals and are thought to account for the majority of inherited traits. In this study, a genome-wide association study (GWAS) was performed to detect regions of association with hematological traits in a three-generation resource population produced by intercrossing Large White boars and Minzhu sows during the period from 2007 to 2011. Illumina PorcineSNP60 BeadChip technology was used to genotype each animal and seven hematological parameters were measured (hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC) and red blood cell volume distribution width (RDW)). Data were analyzed in a three step Genome-wide Rapid Association using the Mixed Model and Regression-Genomic Control (GRAMMAR-GC) method. A total of 62 genome-wide significant and three chromosome-wide significant SNPs associated with hematological parameters were detected in this GWAS. Seven and five SNPs were associated with HCT and HGB, respectively. These SNPs were all located within the region of 34.6-36.5 Mb on SSC7. Four SNPs within the region of 43.7-47.0 Mb and fifty-five SNPs within the region of 42.2-73.8 Mb on SSC8 showed significant association with MCH and MCV, respectively. At chromosome-wide significant level, one SNP at 29.2 Mb on SSC1 and two SNPs within the region of 26.0-26.2 Mb were found to be significantly associated with RBC and RDW, respectively. Many of the SNPs were located within previously reported QTL regions and appeared to narrow down the regions compared with previously described QTL intervals. In current research, a total of seven significant SNPs were found within six candidate genes SCUBE3, KDR, TDO, IGFBP7, ADAMTS3 and AFP. In addition, the KIT gene, which has been previously reported to relate to hematological parameters, was located within the region significantly associated with MCH and MCV and could be a candidate gene. These results of this study may lead to a better understanding of the molecular mechanisms of hematological parameters in pigs.

SUBMITTER: Luo W

PROVIDER: S-EPMC3385009 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genome-wide association study of porcine hematological parameters in a Large White × Minzhu F2 resource population.

Luo Weizhen W Chen Shaokang S Cheng Duxue D Wang Ligang L Li Yong Y Ma Xiaojun X Song Xin X Liu Xin X Li Wen W Liang Jing J Yan Hua H Zhao Kebin K Wang Chuduan C Wang Lixian L Zhang Longchao L

International journal of biological sciences 20120615 6

Hematological traits, which are important indicators of immune function in animals, have been commonly examined as biomarkers of disease and disease severity in humans and animals. Genome-wide significant quantitative trait loci (QTLs) provide important information for use in breeding programs of animals such as pigs. QTLs for hematological parameters (hematological traits) have been detected in pig chromosomes, although these are often mapped by linkage analysis to large intervals making identi ...[more]

PMID: 22745577

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Project description:The number of vertebrae (NV), especially the number of thoracic vertebrae (NTV), varies among pig breeds. The NTV is controlled by vertebral segmentation and the number of somites during embryonic development. Although there is a high correlation between the NTV and NV, studies on a fixed NV have mainly considered the absolute numbers of thoracic vertebrae instead of vertebral segmentation. Therefore, this study aimed to discover variants associated with the NTV by considering the effect of the NV in pigs. The NTV and NV of 542 F2 individuals from a Large White × Minzhu pig crossbreed were recorded. All animals were genotyped for VRTN g.19034 A > C, LTBP2 c.4481A > C, and 37 missense or splice variants previously reported in a 951-kb interval on SSC7 and 147 single nucleotide polymorphisms (SNPs) on SSC14. To identify NTV-associated SNPs, we firstly performed a genome-wide association study (GWAS) using the Q + K (population structure + kinship matrix) model in TASSEL. With the NV as a covariate, the obtained data were used to identify the SNPs with the most significant genome-wide association with the NTV by performing a GWAS on a PorcineSNP60K Genotyping BeadChip. Finally, a conditional GWAS was performed by fixing this SNP. The GWAS showed that 31 SNPs on SSC7 have significant genome-wide associations with the NTV. No missense or splice variants were found to be associated with the NTV significantly. A linkage disequilibrium analysis suggested the existence of quantitative trait loci (QTL) in a 479-Kb region on SSC7, which contained a critical candidate gene FOS for the NTV in pigs. Subsequently, a conditional GWAS was performed by fixing M1GA0010658, the most significant of these SNPs. Two SNPs in BMPR1A were found to have significant genome-wide associations and a significant dominant effect. The leading SNP, S14_87859370, accounted for 3.86% of the phenotypic variance. Our study uncovered that regulation variants in FOS on SSC7 and in BMPR1A on SSC14 might play important roles in controlling the NTV, and thus these genetic factors may be harnessed for increasing the NTV in pigs.

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Dataset Information

Genome-wide association study of porcine hematological parameters in a Large White × Minzhu F2 resource population.

Publications

Genome-wide association study of porcine hematological parameters in a Large White × Minzhu F2 resource population.

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