THE GENETIC EPIDEMIOLOGY OF PATTERNS OF HUMAN GROWTH

增长模式变化的遗传流行病学将是 调查是为了更全面地了解基因 以及影响人类长期成长模式的家庭因素。 与增长相关的变量的高度可靠、广泛的序列数据 具有众所周知的健康意义将被用来研究遗传 对这些变量的变化模式的影响。 在FELS纵向生长研究中，测量了生长数据 从出生到成年每半年一次，600多名参与者参加 许多大家庭(大家庭)。增长模式将是 使用数学模型来描述这些数据，这些模型将允许 生物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)已经被 被选中，并将进行研究，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实现。 生长模式性状与限制性片段长度多态之间的关系 (RFLP)靠近候选基因(即这些基因的标记)。这个 在候选基因已知距离内的RFLP将被识别 应用限制性核酸酶分析有核血细胞中的DNA 它们通过电泳法分离，然后杂交并 放射自显影。 选定的候选基因包括与生长抑素、生长相关的基因 激素、绒毛膜促生长激素、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基因附近发生的多态 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。结果就是这样 研究，将获得有关人类生长模式的信息， 生长相关基因的多态及其相关性 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 这项研究的主要目的是确定主要基因在多大程度上 解释人类成长模式和成人地位的差异。 这些分析将涵盖许多统计和现代遗传学 流行病学方法，包括检查病毒的分布 衍生的生长模式变量，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之间的联系 初始研究的SIB对方法和最大似然程序 获得常规对数优势比(LOD)分数。

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.