BUILDING A CENTER OF BIOMEDICAL RESEARCH EXCELLENCE

超出提供的空间。 阿拉斯加原住民几千年来在有限的食物资源下，在极端的环境条件下生存下来。 尽管阿拉斯加人的传统饮食中脂肪含量很高，但他们几乎没有肥胖、心脏病和糖尿病的迹象。近期 文化适应导致了更久不动的生活方式，更多的酒精消费，更多的吸烟，以及向 高碳水化合物的西式饮食。伴随着饮食和生活方式的这些变化，肥胖、糖尿病、 心脏病、中风等癌症在阿拉斯加当地人中呈上升趋势。他们对饮食变化的怀疑可以解释 部分原因是节俭假说，它表明生活在恶劣环境中的人食物不稳定 供应通过最大限度地储存剩余能量来提高它们的生存概率。鉴定出的基因 影响阿拉斯加原住民的能量平衡是干预的一个重要方面，因为相关等位基因的知识 变异使人们能够前瞻性地评估个人的疾病风险，并评估 环境、营养和遗传因素在肥胖继发的健康问题发展中的作用。阿拉斯加原住民 代表了一个独特的未被探索的群体，这可能是识别肥胖症等复杂疾病基因的理想选择，因为 它们地理上的隔绝、共享的环境、较小的种群规模和最小的遗传混合 与其他原住民相比，相对更大的遗传同质性，并可能增加了不平衡 美国人口。由于肥胖是许多疾病发展的主要风险因素，因此越来越常见 在阿拉斯加原住民中，拟议研究的总体目标是收集成功的 识别可能使阿拉斯加原住民肥胖的基因。这将通过以下方式实现：(1)确定 通过DNA池-基因组扫描方法获得与肥胖相关的标记；(2)进行基于家庭的连锁 不平衡测试以评估特定候选基因对阿拉斯加原住民肥胖表型的影响；以及 (3)招聘新教师：HAT将扩大阿拉斯加大学的智力资本。肥胖症的遗传学分析 在阿拉斯加原住民与阿拉斯加大学的新教师和一个强大的 哥伦比亚大学、杜克大学和阿拉巴马大学伯明翰分校的研究人员将在 开发宝贵的遗传资源，以及增加我们对遗传变异和 美洲原住民的肥胖倾向。

EXCEED THE SPACE PROVIDED. Alaska Natives have survived extreme environmental conditions with limited food resources for thousands of years. Despite a traditional diet high in fat,Alaska Natives have evidenced little obesity, heart disease and diabetes. Recent acculturation has led to a more sedentary lifestyle, increased alcohol consumption, more smoking and a shift towards a western diet high in carbohydrates. Along with these changes in diet and lifestyle, the prevalence of obesity, diabetes, heart disease, stroke ar.dcancer is increasing in AlaskaNatives. Their suseptibility to alterations in diet may beexplained in part by the 'thrifty gsne' hypothesiswhich suggests that individuals living in a harsh environmentwith an unstable food supply enhance their probability of survival by maximizing storage of surplus energy. Identification of genes that influence energy balance in Alaska Natives is an important aspect of intervention because knowledge of relevant allelic variation allows one to prospectively evaluate an individual's risk for disease, and to assess the combined influence of environmental, nutritionaland genetic factors in the development of health problems secondary to obesity. Alaska Natives represent a unique unexplored population that may be ideal to identify genes for complex disorders like obesity because their geographic isolation, shared environment, small population size, and minimal genetic admixture have contributed to relatively greater genetic homogeniety, and presumably increased disequilibrium, when compared to other Native American populations. Since obesity is a major risk factor for the development of many diseases increasingly common among Alaska Natives, the overall goal of the proposed research is to collect essential baseline data for the successful identification of genes which may predispose Alaska Natives to obesity. This will be accomplished by: (1) identify markers, associated with obesity by DNA pooling-genome scan approaches; (2) conducting family-based linkage disequilibrium testing to assess the effects of specific candidate genes on the obesity phenotypes in Alaska Natives; and (3) hiring new faculty :hatwill expand intellectualcapital at the University of Alaska. Analysis of the genetics of obesity in Alaska Natives in collaboration with new faculty at the University of Alaska and a strong mentoring group of researchers at Columt ia University, Duke University, and the University of Alabama Birmingham will result in the development of a valuable genetic resource, as well as increase our understanding of the genetic variation and predisposition towards obesity in Native Americans.