NONDISJUNCTION AND PHENOTYPES IN DOWN SYNDROME

21三体是与95%以上的唐氏综合症（DS）相关的染色体异常，是导致智力迟钝的最重要遗传原因，估计发病率为1/600活产。尽管21三体的发生率高且具有明显的临床意义，但我们对21三体的起源机制或可能导致21染色体不分离的因素所知甚少。在拟议的研究中，我们打算结合细胞遗传学，分子和流行病学方法来解决这些问题。在一组调查中，我们将关注21三体的起源，开展研究以确定异常重组和父亲不分离的影响，特别强调检查母亲年龄与21三体之间的关系。在相关研究中，我们将调查特定环境暴露可能影响21三体发病频率的假设，并证实或反驳吸烟和口服避孕药这两个因素是21三体发病危险因素的初步观察结果。

Trisomy 21, the chromosome abnormality associated with over 95% of Down syndrome (DS), is the most important genetic cause of mental retardation, with an estimated incidence of 1/600 livebirths. Despite its high rate of occurrence and obvious clinical importance, we still know surprisingly little about the mechanism of origin of trisomy 21 or about factors which may predispose to non-disjunction of chromosome 21. In the proposed studies, we intend to combine cytogenetic, molecular and epidemiological approaches to address these questions. In one set of investigations we will focus on the genesis of trisomy 21, conducting studies to determine the effect of aberrant recombination and paternal non-disjunction, with particular emphasis on examining the association between maternal age and trisomy 21. In companion studies, we will investigates the hypothesis that specific environmental exposures may influence the frequency of trisomy 21, and confirm or refute preliminary observations that two such factors-smoking and oral contraceptive use-are risk factors for trisomy 21.