Large-scale association study on daily weight gain in pigs reveals overlap of genetic factors for growth in humans.

Large-scale association study on daily weight gain in pigs reveals overlap of genetic factors for growth in humans.
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对猪日增重的大规模关联研究揭示了人类生长的遗传因素重叠。

DOI:
10.1186/s12864-022-08373-3
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发表时间:
2022-02-15
期刊:
影响因子:
4.4
通讯作者:
Sahana G
Sahana G
中科院分区:
生物学2区
文献类型:
--
作者:
Cai Z;Christensen OF;Lund MS;Ostersen T;Sahana G

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从基因分型阵列到全基因组序列变异的插补,使用代表性参考群体的重测序增强了我们绘制影响家畜物种复杂表型的遗传因素的能力。人类和实验动物基因功能知识的积累可以为家畜的基因组研究提供实质性的优势。在这项研究中,来自三个商业丹麦品种的201,388头猪用低到中等(8.5k到70 k)SNP阵列进行基因分型,使用两步法将其插补到全基因组序列变异中。两个插补步骤都实现了高准确度,总共在18个常染色体上产生了26,447,434个标记。次要等位基因频率≥ 0.05的标记的平均估计插补准确度为0.94。为了克服对每个品种进行全基因组关联研究(GWAS)的内存消耗,我们进行了品种内亚群GWAS,然后对平均日增重(ADG)进行了品种内荟萃分析,然后对GWAS汇总统计进行了多品种荟萃分析。我们确定了15个数量性状位点(QTL)。我们的后GWAS分析策略优先考虑候选基因,包括基因本体论,哺乳动物表型数据库,高和低饲料效率猪的差异表达基因分析以及人类GWAS目录中的身高,肥胖和体重指数,我们提出了MRAP 2,LEPROT,PMAIP 1,ENSSSCG 0000036234,BMP 2,ELFN 1,LIG 4和FAM 155 A是猪ADG的候选基因。我们的后GWAS分析策略不仅通过与前导SNP的距离,还通过多种生物学证据来源来帮助识别候选基因。此外,所鉴定的QTL与已知与人类生长相关性状相关的基因重叠。GWAS与这个大数据集显示了绘制与猪ADG相关的遗传因素的能力,并增加了我们对哺乳动物物种生长遗传学的理解。在线版本包含补充材料,可通过10.1186/s12864-022-08373-3获得。
Imputation from genotyping array to whole-genome sequence variants using resequencing of representative reference populations enhances our ability to map genetic factors affecting complex phenotypes in livestock species. The accumulation of knowledge about gene function in human and laboratory animals can provide substantial advantage for genomic research in livestock species. In this study, 201,388 pigs from three commercial Danish breeds genotyped with low to medium (8.5k to 70k) SNP arrays were imputed to whole genome sequence variants using a two-step approach. Both imputation steps achieved high accuracies, and in total this yielded 26,447,434 markers on 18 autosomes. The average estimated imputation accuracy of markers with minor allele frequency ≥ 0.05 was 0.94. To overcome the memory consumption of running genome-wide association study (GWAS) for each breed, we performed within-breed subpopulation GWAS then within-breed meta-analysis for average daily weight gain (ADG), followed by a multi-breed meta-analysis of GWAS summary statistics. We identified 15 quantitative trait loci (QTL). Our post-GWAS analysis strategy to prioritize of candidate genes including information like gene ontology, mammalian phenotype database, differential expression gene analysis of high and low feed efficiency pig and human GWAS catalog for height, obesity, and body mass index, we proposed MRAP2, LEPROT, PMAIP1, ENSSSCG00000036234, BMP2, ELFN1, LIG4 and FAM155A as the candidate genes with biological support for ADG in pigs. Our post-GWAS analysis strategy helped to identify candidate genes not just by distance to the lead SNP but also by multiple sources of biological evidence. Besides, the identified QTL overlap with genes which are known for their association with human growth-related traits. The GWAS with this large data set showed the power to map the genetic factors associated with ADG in pigs and have added to our understanding of the genetics of growth across mammalian species. The online version contains supplementary material available at 10.1186/s12864-022-08373-3.
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期刊: BMC genomics
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