Thomas N Simon, Durkie Miranda, Potts Gemma, Sandford Richard, Van Zyl Berendine, Youings Sheila, Dennis Nicholas R, Jacobs Patricia A
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK.
Eur J Hum Genet. 2006 Jul;14(7):831-7. doi: 10.1038/sj.ejhg.5201617. Epub 2006 Apr 12.
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.
染色体特异性LCRs之间的非等位基因同源重组是导致反复出现微缺失和微重复的最常见机制。为了寻找位点特异性差异，我们使用微卫星来确定一系列新发7q11.23染色体缺失（威廉姆斯综合征）、15q11-q13染色体缺失（天使综合征、普拉德-威利综合征）和22q11染色体缺失（迪乔治综合征）以及15q11-q13染色体重复患者的亲本和染色体起源。总体而言，大多数重排是染色体间的，因此是由不等的减数分裂交换引起的，并且母源和父源缺失的数量大致相等。15q11-q13的重复和缺失似乎是由相同机制产生的相互产物。染色体间交换产生的比例在不同缺失之间有所不同，其中22q11最高，15q11-q13最低。然而，亲本和染色体起源并不总是独立的。对于15q11-q13，母源缺失倾向于染色体间的，而父源缺失倾向于染色体内的；对于22q11，染色体内缺失中母源病例可能过多。几个因素可能参与了反复重排的形成，而且这些因素的相对重要性似乎是位点特异性的。
