CORRELATION OF PHENOTYPE AND CHROMOSOMAL ABNORMALITIES

这项研究将联合收割机结合细胞遗传学和分子技术 表征缺失、重复和标记染色体，以及 关联分子和表型变异性。 我们将测试 一种假说，即出现结构异常的染色体 细胞学上相似，实际上分子上不同，我们将 比较可能的结构DNA差异，以澄清临床 一些具有相似核型的患者表现出的异常 异常 具体来说，我们将：1）分子表征和 确定性染色体标记的染色体起源。 （二） 卫星常染色体标记，特别强调inv dup（15） 染色体 3)常染色体非随体染色体起源 标记物，以确定是否存在任何常染色质材料 4）断裂点和量 染色体9 p缺失患者中染色体物质缺失5） 在患有轻微遗传病的患者中，染色体材料缺失/复制的数量 6）如果染色体材料缺失， 在其他患者中删除或复制的此类材料的量 以上未描述的重排。 一般来说，三组不同的染色体 变更将被研究：（1）家庭确定通过propositus 表型异常;（2）有额外或缺失 染色体材料，但无表型异常;和（3） 具有未知表型的染色体异常个体 (i.e.,通过产前诊断确定）。 最低100-150 具有标记染色体或从头重排的先证者将被 研究了

This proposed study will combine cytogenetic and molecular techniques to characterize deletions, duplications and marker chromosomes, and to correlate molecular and phenotypic variability. We will test the hypothesis that structurally abnormal chromosomes which appear cytologically similar, are in fact molecularly different, and we will compare possible structural DNA differences to clarify the clinical abnormalities manifested by some of the patients with similar karyotypic abnormalities. Specifically we will: 1) molecularly characterize and determine the chromosomal origin of sex chromosome markers. 2) satellited autosomal markers, with particular emphasis on inv dup (15) chromosomes. 3) the chromosomal origin of autosomal non-satellited markers to determine if any euchromatic material is present in addition to the detected centromeric material 4) the breakpoint and amount of chromosome material missing in chromosome 9p deletion patients 5) the amount of chromosome material deleted/duplicated in patients with subtle deletions/duplications 6) if chromosomal material is missing and the amount of such material deleted or duplicated in patients with other rearrangements not delineated above. In general, three separate groups of individuals with chromosome alterations will be studied: (1) families ascertained via a propositus with phenotypic abnormalities; (2) families with extra or missing chromosomal material, but with no phenotypic abnormalities; and (3) individuals with a chromosome abnormality with a yet unknown phenotype (i.e., ascertained through prenatal diagnosis). A minimum of 100-150 probands with marker chromosomes or de novo rearrangements will be studied.