GENETIC EPIDEMIOLOGY OF CHILDHOOD SKELETAL MATURATION

拟议研究的最终目标是：1）描述遗传特征 参与整个儿童期骨骼成熟，2）定位和 确定未知基因影响的重要性 儿童时期骨骼成熟的个体差异，以及3） 评估候选基因中多态性的贡献， 儿童时期骨骼成熟的个体差异。 虽然对儿童生长模式和性发育的研究 虽然是很多研究的焦点，但目前对它知之甚少。 参与骨骼成熟的过程。这是尤其是 关于儿童骨骼发育的遗传学 在这一建议中，骨骼成熟，区别于骨骼 生长，指的是这样的过程，即一组特定的放射摄影 骨骼特征的可见变化在成人骨骼状态中达到顶峰 在年轻的成年期。 技能成熟度指的是 考虑到儿童的实际年龄。 Skeleton成熟度是量化的 作为骨龄，指定给骨骼或骨骼区域的值， 以年和月表示的成熟程度， 孩子的实际年龄或实际年龄。 骨骼年龄反映了不同生长阶段的不同机制 发展先行者的要求 在幼儿期，它主要是衡量 骨骼骨化发生的时间。 在童年中期，这主要是 测量骨骼形状的变化，无论是单独的还是相对的， 到联合编队。 在生长和发育的末期， 青春期骨龄很大程度上是衡量骨骺发育程度的指标 核聚变 在拟议的研究中，通过系列X光片评估骨龄 手腕和膝盖的一部分， 纵向研究。 有超过15,500个骨龄评估， 从1930年到现在的手腕X光照片，以及大约7750张 根据1931年至2000年期间拍摄的膝关节X光片评估骨龄 1987年，900多名儿童参加了一次或另一次在 Fels纵向研究，从婴儿期到 至少18年 这些人共代表213个核 和大家庭，其中大多数有家庭成员， 已经收集，或目前正在收集，作为 以前和正在进行的研究。 这些数据提供了一个整体 这是一个前所未有的、彻底独特的机会， 儿童时期骨骼成熟的结构。

The ultimate goals of the proposed study are to: 1) characterize genetic involvement in skeletal maturation throughout childhood, 2) locate and determine the significance of as yet unknown genes influencing individual variation in skeletal maturation during childhood, and 3) evaluate the contributions of polymorphisms in candidate genes to individual variation in skeletal maturation during childhood. While the study of childhood growth patterns and sexual development has been the focus of much study, very little is presently known about processes involved in skeletal maturation. This is especially so regarding the genetics of childhood skeletal maturation. In this proposal, skeletal maturation, as distinguished from skeletal growth, refers to the process whereby sets of specific radiographically visible changes in skeletal features culminate in adult skeletal status in young adulthood. Skeletal maturity refers to status achieved by a given chronological age in childhood. Skeletal maturity is quantified as skeletal age, a value assigned to a bone or skeletal area that is the level of maturity expressed in years and months irrespective of the child's actual or chronological age. Skeletal age reflects different mechanisms at different stages of growth and development. During early childhood, it is largely a measure of the timing of ossification onset in bones. In mid-childhood, it is largely a measure of changes in bone shape, both individually and with respect to joint formation. Near the end of growth and development, during puberty, skeletal age is largely a measure of degree of epiphyseal fusion. Skeletal age is assessed in the proposed study from serial radiographs of the hand-wrist and the knee collected as part of the Fels Longitudinal Study. There are over 15,500 skeletal age assessments from hand-wrist radiographs taken from 1930 to the present, and some 7,750 assessments of skeletal age from knee radiographs taken between 1931 and 1987, of over 900 children participating at one time or another in the Fels Longitudinal Study who have been studied serially from infancy to at least 18 years. These individuals represent a total of 213 nuclear and extended families, most of which have family members from whom DNA has already been collected, or is presently being collected, as part of both previous and ongoing studies. These data offer an altogether unprecedented and thoroughly unique opportunity to elucidate the genetic architecture of skeletal maturation during childhood.