Parental and chromosomal origins of microdeletion and duplication syndromes involving 7q11.23, 15q11-q13 and 22q11
Parental and chromosomal origins of microdeletion and duplication syndromes involving 7q11.23, 15q11-q13 and 22q11
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DOI：
10.1038/sj.ejhg.5201617
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发表时间：
2006-07-01
影响因子：
5.2
通讯作者：
Jacobs, Patricia A.
中科院分区：
文献类型：
--
作者：
Thomas, N. Simon;Durkie, Miranda;Jacobs, Patricia A.
染色体特异性LCR之间的非等位基因同源重组是导致复发性微缺失和重复的最常见机制。为了寻找基因座特异性差异，我们使用微卫星来确定大量染色体7q11.23（威廉姆斯综合征）、15 q11-q13（安格尔曼综合征、普拉德-威利综合征）和22 q11（迪乔治综合征）从头缺失和15 q11-q13重复的患者的父母和染色体起源。总的来说，大多数重排是染色体间的，因此产生于不平等的减数分裂交换，并且有大约相同数量的母本和父本缺失。15 q11-q13的重复和缺失似乎是由相同机制产生的相互产物。22 q11缺失的比例最高，15 q11-q13缺失的比例最低。然而，父母和染色体的起源并不总是独立的。对于15 q11-q13，母亲的缺失倾向于染色体间，而父亲的缺失倾向于染色体内;对于22 q11，在染色体内缺失中可能有过多的母亲病例。有几个因素可能参与形成复发性重排，这些因素的相对重要性似乎是基因座特异性的。
Non- allelic homologous recombination between chromosome- specific LCRs is the most common mechanism leading to recurrent microdeletions and duplications. To look for locus- specific differences, we have used microsatellites to determine the parental and chromosomal origins of a large series of patients with de novo deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome) and duplications of 15q11-q13. Overall the majority of rearrangements were interchromosomal, so arising from unequal meiotic exchange, and there were approximately equal numbers of maternal and paternal deletions. Duplications and deletions of 15q11-q13 appear to be reciprocal products that arise by the same mechanisms. The proportion arising from interchromosomal exchanges varied among deletions with 22q11 the highest and 15q11-q13 the lowest. However, parental and chromosomal origins were not always independent. For 15q11-q13, maternal deletions tended to be interchromosomal while paternal deletions tended to be intrachromosomal; for 22q11 there was a possible excess of maternal cases among intrachromosomal deletions. Several factors are likely to be involved in the formation of recurrent rearrangements and the relative importance of these appear to be locus- specific.