Parental origin of de novo constitutional deletions of chromosomal band 11p13.
Parental origin of de novo constitutional deletions of chromosomal band 11p13.
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DOI：
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发表时间：
1990-07
影响因子：
9.8
通讯作者：
V. Huff;A. Meadows;V. Riccardi;L. Strong;G. Saunders
中科院分区：
文献类型：
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作者：
V. Huff;A. Meadows;V. Riccardi;L. Strong;G. Saunders
Wilms肿瘤（Wilms tumor， WT）是一种儿童肾脏肿瘤，在所有病例中，有一半在染色体带11p13位点上显示杂合性缺失，这表明一个等位基因突变和随后的同源等位基因突变或缺失是这些肿瘤发展中的重要事件。先前报道的这些肿瘤中母体等位基因的非随机丢失表明，原发突变发生在父系遗传的染色体上，并且由于正常母体等位基因的丢失而被“揭露”。这反过来表明，父系遗传的等位基因比母系遗传的更易变。为了研究生发突变在母系遗传染色体和父系遗传染色体中是否具有相同的频率，我们通过对8名儿童及其父母的淋巴细胞DNA进行11p13 RFLPs分型，确定了生发11p13缺失的亲本来源。在8例中，有7例从头缺失是父系起源。在11p13缺失的大小或程度方面，母体起源的一个病例并不显著，孩子确实发展为WT。尽管母体遗传占主导地位，但已报道了双亲平衡易位携带者11p13缺失的传播。这些数据，除了在其他位点父系衍生的新生突变的普遍优势外，表明我们观察到的父系缺失频率的增加是由于男性生发突变率的增加。
One-half of all cases of Wilms tumor (WT), a childhood kidney tumor, show loss of heterozygosity at chromosomal band 11p13 loci, suggesting that mutation of one allele and subsequent mutation or loss of the homologous allele are important events in the development of these tumors. The previously reported nonrandom loss of maternal alleles in these tumors implied that the primary mutation occurred on the paternally derived chromosome and that it was "unmasked" by loss of the normal maternal allele. This, in turn, suggests that the paternally derived allele is more mutable than the maternal one. To investigate whether germinal mutations are seen with equal frequency in maternally versus paternally inherited chromosomes, we determined the parental origin of the de novo germinal 11p13 deletions in eight children by typing lymphocyte DNA from these children and from their parents for 11p13 RFLPs. In seven of the eight cases, the de novo deletion was of paternal origin. The one case of maternal origin was unremarkable in terms of the size or extent of the 11p13 deletion, and the child did develop WT. Transmission of 11p13 deletions by both maternal and paternal carriers of balanced translocations has been reported, although maternal inheritance predominates. These data, in addition to the general preponderance of paternally derived, de novo mutations at other loci, suggest that the increased frequency of paternal deletions we observed is due to an increased germinal mutation rate in males.