THE GENETIC EPIDEMIOLOGY OF PATTERNS OF HUMAN GROWTH

人类生长模式的遗传流行病学

• 批准号: 3328554
• 负责人: ROGER M SIERVOGEL
• 金额: $ 35.65万
• 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/3328554
• 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.

生长模式变化的遗传流行病学将是 为了更全面地了解遗传 影响人类长期生长模式的家庭因素。 与生长相关的变量的高度可靠、广泛的串行数据 具有众所周知的健康意义将用于研究遗传 影响这些变量的变化模式。 在 Fels 纵向生长研究中，测量了生长数据 超过 600 名参与者从出生到成年每半年进行一次 许多大家族（大家庭）。增长模式将是 使用数学模型描述这些数据，这将允许 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 选择并进行研究以确定它们在观察到的生长中的作用 模式。这将通过进行遗传连锁研究来完成 生长模式性状与限制性片段长度多态性之间 （RFLPS）靠近候选基因（即这些基因的标记）。这 RFLPS，在候选基因的已知距离内，将被识别 使用限制性核酸酶分析来自有核血细胞的 DNA 通过电泳分离它们，然后进行杂交 放射自显影。 所选的候选基因包括生长抑素、生长 激素、绒毛膜生长激素、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 因为这项研究是基于这些附近多态性的发生 基因、了解染色体位置以及 DNA 探针的可用性 限制性片段长度多态性研究。结果是 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普遍程度及其关联 家庭内部和家庭之间的生长模式和生长基因之间的关系。一个 该研究的主要目的是确定主要基因在多大程度上 解释人类生长模式和成人状态的差异。 分析将涵盖许多统计和现代遗传学 流行病学方法，包括检查分布情况 导出的生长模式变量、性别调整、识别 关联、分离分析和遗传连锁分析。可能的 将使用以下方法分析增长模式变量与 RFLP 的联系 用于初始研究的同胞对方法和最大似然程序 获得传统的对数比值比 (lod) 分数。