Gene discovery and the genetic basis of inherited disease in non-model organisms

非模式生物的基因发现和遗传性疾病的遗传基础

• 批准号: 326905-2006
• 负责人: Marshall, Heather
• 金额: $ 2.33万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365144
• 关键词: Gene; discovery; genetic; basis; inherited

The novel focus of the present study is to uncover the genetic component of inherited disease in non-model organisms - specifically large mammals that are of commercial and/or conservation interest regionally. The proposed research takes advantage of genomic resources and bioinformatics tools, with the immediate goal of discovering genes responsible for a devastating hereditary condition in silver foxes, and the more general one of illuminating the relationship between genotypic and phenotypic variation in species that, although depauperately represented in PubMed, share a comparatively recent evolutionary history with our own. The specific goals of the research are to determine candidate genes for hereditary hyperplastic gingivitis (gum overgrowth) in foxes, to evaluate the association between the DNA sequence of these genes and disease status of foxes, to compare affected and unaffected foxes at an unlinked putatively neutral genetic locus, and to assay the frequency and distribution of disease-associated genetic variation in natural populations. An additional goal is to investigate the evolutionary origin of the mutation that causes Kermodism in black bears (located on the same gene as red hair in humans) and its uniqueness and adaptive significance among mammals. This research is significant because it uses a human disease to model a furbearing carnivore disease at the molecular level. In addition to providing valuable information to the fur breeding industry, it therefore also contributes to our knowledge of a troublesome human condition. The identification of genes associated with aspects of the cell cycle provides potentially important new tools for cancer research. And studying variation in these genes in both bred and natural populations will contribute to the disentanglement of the complex relationship between genotype and phenotype and ultimately help explain the vast scope of mammalian genetic variation. It is in this latter context that elucidation of the molecular genetic mechanisms of melanism in Kermode bears is important. In addition to its scientific contributions, this research involves the development of new biotechnologies, such as microchip DNA re-sequencing, and forges regional institutional collaborations.

本研究的新重点是揭示非模式生物遗传性疾病的遗传成分-特别是大型哺乳动物，具有商业和/或保护利益的区域。这项研究利用了基因组资源和生物信息学工具，其直接目标是发现导致银狐毁灭性遗传疾病的基因，以及阐明物种中基因型和表型变异之间关系的更普遍的目标，尽管在PubMed中有详细的描述，但与我们自己的进化史相对较近。该研究的具体目标是确定狐狸遗传性增生性牙龈炎（牙龈过度生长）的候选基因，评估这些基因的DNA序列与狐狸疾病状态之间的关联，比较受影响和未受影响的狐狸在一个非连锁的puplex中性遗传位点，并分析自然种群中与疾病相关的遗传变异的频率和分布。另一个目标是研究导致黑熊Kermodism的突变的进化起源（与人类的红头发位于同一基因上）及其在哺乳动物中的独特性和适应性意义。这项研究意义重大，因为它使用人类疾病在分子水平上模拟毛皮食肉动物疾病。除了为毛皮养殖业提供有价值的信息外，它还有助于我们了解人类的困境。与细胞周期相关的基因的鉴定为癌症研究提供了潜在的重要新工具。研究这些基因在人工繁殖和自然种群中的变异将有助于解开基因型和表型之间复杂的关系，并最终有助于解释哺乳动物遗传变异的巨大范围。正是在这后一种情况下，在Kermode熊黑化的分子遗传机制的阐明是重要的。除了科学贡献外，这项研究还涉及开发新的生物技术，如微芯片DNA重新测序，并建立区域机构合作。