THE GENETIC EPIDEMIOLOGY OF PATTERNS OF HUMAN GROWTH

人类生长模式的遗传流行病学

• 批准号: 3328553
• 负责人: ROGER M SIERVOGEL
• 金额: $ 39.71万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3328553
• 关键词: developmental genetics; genetic markers; genetic models; genetic polymorphism; growth /development; growth factor receptors; human genetic material tag; human population genetics; insulinlike growth factor; linkage mapping; longitudinal human study; restriction fragment length polymorphism; somatostatin; somatotropin

The genetic epidemiology of patterns of change in growth will be investigated in order to achieve a more complete understanding of genetic and familial factors influencing long-term growth patterns in human beings. Highly reliable, extensive serial data for growth-related variables that have well-known health significance will be used to study genetic influences on the patterns of change in these variables. In the Fels Longitudinal Growth Study, growth data have been measured semi-annually from birth into adulthood for more than 600 participants in numerous large kindreds (extended families). Growth patterns will be described for these data using mathematical models that will allow the derivation of biologically interpretable growth-pattern variables. Known genes associated with growth regulation (i.e., candidate genes) have been selected and will be studied to determine their role in the observed growth patterns. This will be accomplished by performing genetic linkage studies between growth pattern traits and restriction fragment length polymorphisms (RFLPS) near the candidate genes (i.e., markers for these genes). The RFLPS, within known distances of the candidate genes, will be recognized using restriction nuclease analysis of DNA from nucleated blood cells in which they are isolated by electrophoresis, then hybridized and autoradiographed. The selected candidate genes include those for somatostatin, growth hormone, chorionic somatomammotropin, insulin-like growth factors I and II, insulin and the receptors for insulin and growth hormone. Their selection for this study is based on the occurrence of polymorphisms near these genes, know chromosomal location, and the availability of DNA probes for restriction fragment length polymorphism studies. As a result of this study, information will be obtained concerning patterns of human growth, the prevalence of polymorphisms for growth-related genes, and associations between growth patterns and growth genes within and among families. A primary aim of the study is to establish the extent to which major genes explain the variance in human growth patterns and adult status. The analyses will encompass many statistical and modem genetic epidemiological methodologies including examination of the distributions of derived growth-pattern variables, sex adjustments, identification of associations, segregation analyses, and genetic linkage analyses. Possible linkage of growth pattern variables with the RFLPs will be analyzed using sib-pair methods for initial studies and maximum likelihood procedures to obtain conventional log odds ratio (lod) scores.

生长变化模式的遗传流行病学将是 为了更全面地了解遗传学， 以及影响人类长期生长模式的家庭因素。 高度可靠、广泛的增长相关变量的串行数据， 具有众所周知的健康意义将被用于研究遗传 影响这些变量的变化模式。 在Fels纵向生长研究中， 从出生到成年，每半年为600多名参与者提供一次 大家族（extended families）增长模式将是 使用数学模型描述这些数据， 生物学上可解释的生长模式变量的推导。已知 与生长调节相关的基因（即，候选基因）已被 选择并将进行研究，以确定它们在观察到的增长中的作用 模式.这将通过进行遗传连锁研究来完成 限制性片段长度多态性 （RFLPS）在候选基因附近（即，这些基因的标记）。的 在候选基因的已知距离内的RFLPS将被识别 使用限制性核酸酶分析来自有核血细胞的DNA， 它们通过电泳分离，然后杂交， 放射自显影的 所选择的候选基因包括生长抑素、生长抑制素、 激素、绒毛膜生长催乳素、胰岛素样生长因子I和II， 胰岛素以及胰岛素和生长激素的受体。他们的选择 这项研究的基础是在这些基因附近发生多态性， 基因，知道染色体位置，以及DNA探针的可用性， 限制性片段长度多态性研究。由于这种 通过这项研究，将获得有关人类生长模式的信息， 生长相关基因多态性的患病率， 生长模式和生长基因之间的联系。一 研究的主要目的是确定主要基因在多大程度上 解释了人类生长模式和成年状态的差异。 分析将包括许多统计和现代遗传学 流行病学方法，包括检查 衍生的增长模式变量，性别调整， 关联、分离分析和遗传连锁分析。可能 生长模式变量与RFLP的联系将使用 用于初始研究的同胞配对方法和最大似然程序， 获得常规对数比值比（LOD）分数。