Copy Number Variations Contribute to Intramuscular Fat Content Differences by Affecting the Expression of PELP1 Alternative Splices in Pigs.
Copy Number Variations Contribute to Intramuscular Fat Content Differences by Affecting the Expression of PELP1 Alternative Splices in Pigs.
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拷贝数变异通过影响猪中 PELP1 选择性剪接的表达而导致肌内脂肪含量差异
DOI：
10.3390/ani12111382
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发表时间：
2022-05-27
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影响因子：
--
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拷贝数变异（CNV）是一种可能影响肉质的变异类型，例如肌内脂肪（IMF）。在这项研究中，全基因组关联研究（GWAS）之间的CNVs和IMF在猪F2资源群体。共发现19个CNVRs与IMF显著相关。RNA-seq和qPCR验证结果表明，位于脯氨酸3′UTR端的CNV 150以及谷氨酸和富亮氨酸蛋白1（PELP 1）基因可能影响PELP 1可变剪接体的表达。我们推断CNVR可能通过调节PELP 1基因的选择性剪接来影响IMF含量，并最终影响PELP 1蛋白的结构。这些发现为改善动物肉质和治疗人类胰岛素抵抗提供了一种新的机制。摘要肌内脂肪（IMF）是肉的重要品质性状。研究IMF分解的遗传机制对改善猪肉品质、治疗肥胖和2型糖尿病具有重要意义。拷贝数变异（CNV）是一种可能影响肉质的变异类型。在这项研究中，共1185 CNVRs（CNVRs），包括393个重复CNVRs，432个缺失CNVRs，和361个CNVRs与重复和缺失的状态，在猪F2资源群体中使用新一代测序数据进行鉴定。然后在CNVs和IMF之间进行全基因组关联研究（GWAS），共发现19个CNVRs与IMF显著相关。QTL共定位分析表明，19个CNVRs中有3个与已知QTL重叠。RNA-seq和qPCR验证结果表明，位于脯氨酸3′UTR端的CNV 150以及谷氨酸和富亮氨酸蛋白1（PELP 1）基因可能影响PELP 1可变剪接体的表达。序列比对和Alphafold 2结构预测结果表明，PELP 1的两个可变剪接体存在23个氨基酸的序列变异和一个螺旋折叠结构变异。该区域位于PELP 1和其他蛋白质之间的相互作用区域，这些蛋白质已被报道与脂肪沉积或胰岛素抵抗显著相关。我们推断CNVR可能通过调节PELP 1基因的选择性剪接来影响IMF含量，并最终影响PELP 1蛋白的结构。总之，我们发现位于PELP 1的CNVRs，特别是CNV 150，影响IMF。这些发现为改善动物肉质和治疗人类胰岛素抵抗提供了一种新的机制。
Simple Summary Copy number variation (CNV) is a type of variant that may influence meat quality of, for example intramuscular fat (IMF). In this study, a genome-wide association study (GWAS) was then performed between CNVs and IMF in a pig F2 resource population. A total of 19 CNVRs were found to be significantly associated with IMF. RNA-seq and qPCR validation results indicated that CNV150, which is located on the 3′UTR end of the proline, as well as glutamate and the leucine rich protein 1 (PELP1) gene may affect the expression of PELP1 alternative splices. We infer that the CNVR may influence IMF content by regulating the alternative splicing of the PELP1 gene and ultimately affects the structure of the PELP1 protein. These findings suggest a novel mechanistic approach for meat quality improvement in animals and the potential treatment of insulin resistance in human beings. Abstract Intramuscular fat (IMF) is a key meat quality trait. Research on the genetic mechanisms of IMF decomposition is valuable for both pork quality improvement and the treatment of obesity and type 2 diabetes. Copy number variations (CNVs) are a type of variant that may influence meat quality. In this study, a total of 1185 CNV regions (CNVRs) including 393 duplicated CNVRs, 432 deleted CNVRs, and 361 CNVRs with both duplicated and deleted status were identified in a pig F2 resource population using next-generation sequencing data. A genome-wide association study (GWAS) was then performed between CNVs and IMF, and a total of 19 CNVRs were found to be significantly associated with IMF. QTL colocation analysis indicated that 3 of the 19 CNVRs overlapped with known QTLs. RNA-seq and qPCR validation results indicated that CNV150, which is located on the 3′UTR end of the proline, as well as glutamate and the leucine rich protein 1 (PELP1) gene may affect the expression of PELP1 alternative splices. Sequence alignment and Alphafold2 structure prediction results indicated that the two alternative splices of PELP1 have a 23 AA sequence variation and a helix-fold structure variation. This region is located in the region of interaction between PELP1 and other proteins which have been reported to be significantly associated with fat deposition or insulin resistance. We infer that the CNVR may influence IMF content by regulating the alternative splicing of the PELP1 gene and ultimately affects the structure of the PELP1 protein. In conclusion, we found some CNVRs, especially CNV150, located in PELP1 that affect IMF. These findings suggest a novel mechanistic approach for meat quality improvement in animals and the potential treatment of insulin resistance in human beings.
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影响因子：
3.7
作者：
Huang T;Li J;Jia B;Sang H
通讯作者：
Sang H
影响因子：
14.9
作者：
Hu ZL;Park CA;Reecy JM
通讯作者：
Reecy JM
影响因子：
3.7
作者：
Revilla M;Puig-Oliveras A;Castelló A;Crespo-Piazuelo D;Paludo E;Fernández AI;Ballester M;Folch JM
通讯作者：
Folch JM
DOI：
10.5713/ajas.16.0562
发表时间：
2017-08
期刊：
Asian-Australasian journal of animal sciences
影响因子：
--
作者：
Park HB;Han SH;Yoo CK;Lee JB;Kim JH;Baek KS;Son JK;Shin SM;Lim HT;Cho IC
通讯作者：
Cho IC
影响因子：
3.3
作者：
Estelle, J.;Gil, F.;Perez-Enciso, M.
通讯作者：
Perez-Enciso, M.