Identification and validation of a novel candidate gene regulating net meat weight in Simmental beef cattle based on imputed next-generation sequencing.

Identification and validation of a novel candidate gene regulating net meat weight in Simmental beef cattle based on imputed next-generation sequencing.
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DOI:
10.1111/cpr.12870
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发表时间:
2020-09
期刊:
影响因子:
8.5
通讯作者:
Li J
Li J
中科院分区:
生物学1区
文献类型:
--
作者:
Bordbar F;Jensen J;Du M;Abied A;Guo W;Xu L;Gao H;Zhang L;Li J

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全基因组关联研究是检测家畜重要经济性状候选基因的有效方法。我们的目标是识别有希望的影响净肉重(NMW)的肌肉发育基因,并在牛身上验证这些候选基因。利用下一代测序(NGS)数据集,应用1,252头西门塔尔牛的约1200万个单核苷酸多态(SNPs),通过线性混合模型方法检测影响净产肉量的基因。使用单倍型和连锁不平衡(LD)块来增强对已识别基因的支持。为了研究MTPN在牛肌肉发育中的作用,我们从牛胎儿背最长肌中分离出成肌细胞,并对其在增殖、分化和肥大过程中进行处理。我们确定了一个SNP(Rs100670823)超过了我们的严格意义阈值(P=85.58×10QTL 8),这是一个可能的与−相关的数量性状基因座。我们发现了一个有希望的候选基因--肌营养因子(MTPN),该基因位于该SNP附近区域,它能刺激六个肌肉相关标志物的分化和成肌细胞的融合。在肥大过程中,肌营养素促进肌管肥大,增加肌管直径。细胞存活率测定和流式细胞仪检测显示,肌营养因子抑制成肌细胞的增殖。目前的实验表明,肌营养素促进了骨骼肌细胞的分化和肥大,但抑制了它们的增殖。我们通过体外生物学研究对GWAS结果的检验,为肌营养素在提高牛产肉量方面的潜在应用提供了新的信息,并为进一步的研究提供了有用的信息。全基因组关联研究发现,与牛净肉重(NMW)性状相关的肌营养素(MTPN)能抑制牛成肌细胞的增殖,促进成肌细胞分化和肥大。
Genome‐wide association studies (GWAS) represent a powerful approach to detecting candidate genes for economically important traits in livestock. Our aim was to identify promising candidate muscle development genes that affect net meat weight (NMW) and validate these candidate genes in cattle. Using a next‐generation sequencing (NGS) dataset, we applied ~ 12 million imputed single nucleotide polymorphisms (SNPs) from 1,252 Simmental cattle to detect genes influencing net meat yield by way of a linear mixed model method. Haplotype and linkage disequilibrium (LD) blocks were employed to augment support for identified genes. To investigate the role of MTPN in bovine muscle development, we isolated myoblasts from the longissimus dorsi of a bovine foetus and treated the cells during proliferation, differentiation and hypertrophy. We identified one SNP (rs100670823) that exceeded our stringent significance threshold (P = 8.58 × 10−8) for a putative NMW‐related quantitative trait locus (QTL). We identified a promising candidate gene, myotrophin (MTPN), in the region around this SNP Myotrophin had a stimulatory effect on six muscle‐related markers that regulate differentiation and myoblast fusion. During hypertrophy, myotrophin promoted myotube hypertrophy and increased myotube diameters. Cell viability assay and flow cytometry showed that myotrophin inhibited myoblast proliferation. The present experiments showed that myotrophin increases differentiation and hypertrophy of skeletal muscle cells, while inhibiting their proliferation. Our examination of GWAS results with in vitro biological studies provides new information regarding the potential application of myotrophin to increase meat yields in cattle and helpful information for further studies. Myotrophin (MTPN) found associated with bovine net meat weight (NMW) trait by genome‐wide association studies (GWAS), inhibited bovine myoblasts proliferation and enhanced myogenic differentiation and hypertrophy.
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