Genetics of MODY in families of African Descent

非洲人后裔家族中 MODY 的遗传学

• 批准号: 6364495
• 负责人: MARKUS STOFFEL
• 金额: $ 31.73万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6364495
• 关键词: African Caribbean; autosomal dominant trait; biotechnology; clinical research; diabetes mellitus genetics; disease /disorder onset; family genetics; gel electrophoresis; gene expression; gene mutation; genetic markers; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; insulin sensitivity /resistance; linkage mapping; noninsulin dependent diabetes mellitus; pancreatic islet function; phenotype; polymerase chain reaction; radioimmunoassay

DESCRIPTION (Investigator's abstract): Type 2 diabetes among youth, particularly in children of African descent, is an emerging public health problem for which there is a great potential to improve primary and secondary prevention. Increasing evidence indicates that type 2 diabetes is a complex genetic disorder in which defects in insulin action and insulin secretion contribute to the phenotype expression of the disease. In this application we propose a series of genetic and clinical studies to elucidate the genetic basis of maturity-onset diabetes of the young (MODY) in families of African descent. In contrast to a multitude of studies on the genetic etiology of MODY in Caucasian and Asian pedigrees, no family-based studies have been carried out in pedigrees of African descent. In studies initiated in 1996, pedigrees with early-onset type 2 diabetes and autosomal-dominant inheritance were ascertained from Jamaica and the U.S., and DNA was isolated from a total of eight families, two of which are large enough to independently establish linkage. In this application we propose to apply modern methods in human genetics and clinical investigation to characterize the physiologic defect and identify the MODY gene(s) in these pedigrees. The identification of genes that cause early-onset type 2 diabetes in people of African descent is expected to have a major impact on our understanding of its pathogenesis and possibly of the more common polygenic forms of type 2 diabetes. Furthermore, the identification of the causal genes will likely reveal new physiological pathways and may lead to identification of new drug targets and, ultimately, the development of new, less empirical therapies.

描述（研究者的摘要）：青年中的2型糖尿病， 特别是在非洲血统的儿童中，是新兴的公共卫生 有巨大潜力可以改善初级和次要的问题 预防。越来越多的证据表明2型糖尿病是一个复杂的 胰岛素作用和胰岛素分泌缺陷的遗传疾病 有助于疾病的表型表达。在此应用中，我们 提出一系列遗传和临床研究以阐明遗传基础 非洲血统家族中年轻人（Mody）的成熟度糖尿病的成熟度。 与关于Mody遗传病因的大量研究相反 高加索人和亚洲血统书，没有进行基于家庭的研究 非洲血统的血统。在1996年启动的研究中， 确定了早发2型糖尿病和常染色体主导遗传 来自牙买加和美国，DNA从总共八个家庭中隔离， 其中两个足够大，可以独立建立联系。在这个 我们建议在人类遗传学和临床上应用现代方法 调查以表征生理缺陷并识别Mody 这些谱系中的基因。 鉴定引起早发早发2型糖尿病的基因 预计非洲血统将对我们对它的理解产生重大影响 发病机理，可能是2型的更常见的多基因形式 糖尿病。此外，因果基因的鉴定可能会 揭示新的生理途径，并可能导致新药的识别 目标，最终是新的，较少的经验疗法的发展。