Development and Genome Sequence of a Laboratory-Inbred Miniature Pig Facilitate Study of Human Diabetic Disease

Development and Genome Sequence of a Laboratory-Inbred Miniature Pig Facilitate Study of Human Diabetic Disease
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实验室近交小型猪的发育和基因组序列促进人类糖尿病的研究

DOI:
10.2139/ssrn.3363854
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发表时间:
2019
期刊:
影响因子:
5.8
通讯作者:
Ganqiu Lan
Ganqiu Lan
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Li Zhang;Y.N. Huang;Meng Wang;Yafen Guo;Jing Liang;Xiurong Yang;Wenjing Qi;Yanjun Wu;Jinglei Si;Siran Zhu;Zhe Li;Chao Shi;Shuo Wang;Qun-Jie Zhang;Zhonglin Tang;Lixian Wang;Kui Li;Ruiqiang Li;Ji-Feng Fei;Ganqiu Lan

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猪已被证明是用于糖尿病疾病研究的有价值的大型动物模型。然而,鉴于其独特的解剖学和生理学,它们的转化价值是有限的。近30年来,我们通过长期选择性近交,从原始巴马香猪(BX)中培育出实验室亚洲小型猪自交系(巴马小型猪,BM)。在这里,我们组装了全染色体尺度分辨率的 BM 参考基因组,总长度为 2.49 Gb。比较和进化基因组分析发现了BM和商品猪(杜洛克)之间的许多变异,特别是与有利于糖尿病研究的特征相关的遗传位点中的变异。重测序分析揭示了许多与近亲繁殖和其他选择力相关的分化基因位点。这些与糖尿病猪模型的转录组分析一起,为抵抗糖尿病环境,特别是与能量代谢相关的环境提供了全面的遗传基础。
Pig has been proven to be a valuable large animal model used for research on diabetic disease. However, their translational value is limited given their distinct anatomy and physiology. For the last 30 years, we have been developing a laboratory Asian miniature pig inbred line (Bama miniature pig, BM) from the primitive Bama xiang pig (BX) via long-term selective inbreeding. Here, we assembled a BM reference genome at full chromosome-scale resolution with a total length of 2.49 Gb. Comparative and evolutionary genomic analyses identified numerous variations between the BM and commercial pig (Duroc), particularly those in the genetic loci associated with the features advantageous to diabetes studies. Resequencing analyses revealed many differentiated gene loci associated with inbreeding and other selective forces. These together with transcriptome analyses of diabetic pig models provide a comprehensive genetic basis for resistance to diabetogenic environment, especially related to energy metabolism.
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