Study on genetic factors controlling liver copper concentration in sheep

控制绵羊肝铜浓度的遗传因素研究

• 批准号: 421545351
• 负责人: Professorin Dr. Gesine Lühken
• 金额: --
• 依托单位: Lehrstuhl für Tierzucht und Haustiergenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/421545351?language=en
• 关键词: Study; genetic; factors; controlling; liver

Sheep are known to be impaired regarding their ability to excrete excess copper (Cu) from the liver and therefore to be more susceptible to Cu intoxication than other farm animals. On the other hand, Cu deficiency is also a known problem in sheep husbandry. In consequence, there is little scope for adequate Cu supplementation in the sheep diet. Interestingly, the susceptibility for Cu deficiency as well as for Cu intoxication varies between sheep breeds. Moreover, liver copper concentration seems to be highly heritable and variable between and within sheep breeds. Hence, it is the aim of this study to identify the molecular genetic factors which significantly control the liver copper concentration in sheep. In the first part of this project, Cu concentration will be measured in already collected liver samples from performance tested slaughter lambs of the Merinoland sheep breed. Applying an SNP chip, DNA from 96 of these samples will be genotyped for about 600,000 genetic variants distributed in the sheep genome. Resulting phenotyping and genotyping data will be used for a genome wide association study (GWAS). Subsequently, genome regions which showed to be associated with liver Cu concentration will be screened for genetic variants which could directly control liver copper concentration. For this step, an appropriate next generation sequencing method will be employed. Finally, the most promising among those genetic variants will be tested for their effect on liver copper concentration in additionally collected and phenotyped samples from five more sheep breeds, which are of importance in sheep production and/or known to differ in their susceptibility to Cu intoxication or deficiency. The results of this project will enhance the knowledge on the genetic control of liver Cu metabolism and can help to develop new concepts for therapy and prevention of Cu intoxication and deficiency in sheep.

已知绵羊从肝脏排出过量铜（Cu）的能力受损，因此比其他农场动物更容易受到Cu中毒的影响。另一方面，铜缺乏也是绵羊养殖业中的一个已知问题。因此，在绵羊日粮中补充足够的铜的余地很小。有趣的是，铜缺乏症以及铜中毒的易感性在绵羊品种之间存在差异。此外，肝脏铜浓度似乎是高度遗传和变量之间和绵羊品种内。因此，本研究的目的是确定显着控制绵羊肝脏铜浓度的分子遗传因素。在本项目的第一部分，铜浓度将在已经收集的肝脏样品从性能测试屠宰羔羊的美利奴羊品种。应用SNP芯片，将对这些样本中的96个样本的DNA进行基因分型，以确定分布在绵羊基因组中的约60万种遗传变异。所得表型和基因分型数据将用于全基因组关联研究（GWAS）。随后，将筛选显示与肝铜浓度相关的基因组区域，以寻找可直接控制肝铜浓度的遗传变异体。对于该步骤，将采用适当的下一代测序方法。最后，这些遗传变异中最有前途的将测试其对肝脏铜浓度的影响，另外收集和表型样本从五个以上的绵羊品种，这是重要的绵羊生产和/或已知不同的易感性铜中毒或缺乏。本研究的结果将有助于加深对绵羊肝脏铜代谢的遗传控制的认识，并有助于为绵羊铜中毒和铜缺乏症的治疗和预防提供新的概念。