PARENTAL ORIGIN OF THE EXTRA CHROMOSOME IN TRISOMY-21 AS INDICATED BY ANALYSIS OF DNA POLYMORPHISMS
PARENTAL ORIGIN OF THE EXTRA CHROMOSOME IN TRISOMY-21 AS INDICATED BY ANALYSIS OF DNA POLYMORPHISMS
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DOI：
10.1056/nejm199103283241302
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发表时间：
1991-03-28
影响因子：
158.5
通讯作者：
ANTONARAKIS, SE
中科院分区：
文献类型：
--
作者：
ANTONARAKIS, SE
背景。 在过去的 20 年里，人们通过细胞遗传学方法对 21 三体性儿童的额外染色体的父母起源进行了研究，以识别 21 号染色体的形态变异。这些研究得出的结论是，大约 80% 的病例中额外的 21 号染色体起源于母体，约 20% 的病例起源于父体。方法。 我们研究了 200 个家庭，每个家庭都有一个患有 21 三体性的孩子，使用 DNA 多态性作为标记来确定导致额外 21 号染色体不分离的父母起源。这些多态性跨越 21 号染色体长臂上约 120 厘摩的区域，从 D21S13 基因座（最着丝粒）到 COL6A1 基因（最端粒）。结果。 200 名儿童中，除 7 名外，其他所有儿童都可以确定不分离的父母根源。 184 名儿童为母亲（比例 [+/- SE]，95.3 +/- 1.5%），9 名儿童为父亲（4.7 +/- 1.5%）。 在 31 个家族的亚组中，我们将 DNA 分析的结果与传统细胞遗传学分析的结果进行了比较。 根据细胞遗传学分析，26 例（84%）不分离起源于母亲，5 例（16%）起源于父亲。 DNA 分析表明，29 例（94%）的患者源自母系，2 例（6%）的患者源自父系。 通过细胞遗传学分析，存在三个错误的父系起源判断。结论。 在 21 三体中，大约 95% 的病例中额外的 21 号染色体来自母体，而只有大约 5% 的病例来自父体，这比细胞遗传学方法报道的要少得多。 DNA 多态性分析现在是确定不分离亲本起源的首选方法。
Background. Over the past 20 years, the parental origin of the extra chromosome in children with trisomy 21 has been investigated with cytogenetic methods of identifying morphologic variations in chromosome 21. These studies have concluded that the origin of the extra chromosome 21 was maternal in approximately 80 percent of cases and paternal in about 20 percent.Methods. We studied 200 families, each with a single child with trisomy 21, using DNA polymorphisms as markers to determine the parental origin of the nondisjunction causing the extra chromosome 21. These polymorphisms spanned a region of about 120 centimorgans on the long arm of chromosome 21, from the D21S13 locus (the most centromeric) to the COL6A1 gene (the most telomeric).Results. The parental origin of nondisjunction could be determined for all but 7 of the 200 children. It was maternal in 184 children (proportion [+/- SE], 95.3 +/- 1.5 percent) and paternal in 9 (4.7 +/- 1.5 percent). In a subgroup of 31 families, we compared the results of DNA analysis with those of traditional cytogenetic analysis. According to the cytogenetic analyses, nondisjunction originated in the mother in 26 cases (84 percent) and in the father in 5 (16 percent). DNA analysis demonstrated the origin as maternal in 29 (94 percent) and paternal in 2 (6 percent). With the cytogenetic analyses, there were three false determinations of paternal origin.Conclusions. In trisomy 21 the extra chromosome 21 is maternal in origin in about 95 percent of the cases, and paternal in only about 5 percent - considerably less than has been reported with cytogenetic methods. DNA polymorphic analysis is now the method of choice for establishing the parental origin of nondisjunction.