NONDISJUNCTION AND PHENOTYPES IN DOWN SYNDROME

21三体是一种染色体异常，与95%以上的唐氏综合征（DS）相关，是智力低下的最重要遗传原因，估计发病率为1/600活产婴儿。尽管21三体的发生率高，临床意义明显，但我们对21三体的起源机制以及可能导致21号染色体不分离的因素仍然知之甚少。在拟议的研究中，我们打算结合联合收割机细胞遗传学，分子和流行病学的方法来解决这些问题。在一组调查中，我们将集中在21三体的起源，进行研究，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和21三体之间的关联。在伴随研究中，我们将调查特定环境暴露可能影响21三体发生频率的假设，并证实或反驳初步观察结果，即吸烟和口服避孕药使用是21三体的危险因素。

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.