Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis
Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis
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DOI：
10.1093/hmg/9.4.489
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发表时间：
2000-03-01
影响因子：
3.5
通讯作者：
Emanuel, BS
中科院分区：
文献类型：
--
作者：
Shaikh, TH;Kurahashi, H;Emanuel, BS
22q11.2缺失综合征是最常见的微缺失综合征，包括DiGeorge综合征和腭心面综合征（DGS/VCFS）。大多数缺失的患者共享22q11.2的常见3 Nib半合子缺失。其余患者包括具有嵌套在3 Mb典型缺失区（TDR）内的较小缺失的患者和少数具有与TDR不重叠的罕见缺失的患者。染色体22特异性重复序列或低拷贝重复序列（LCR）的3 Mb TDR的端点附近的鉴定导致了假设，他们介导的22q11.2的缺失。整个3 Mb的TDR已经测序，允许详细调查LCR及其参与22q11.2缺失。序列分析在3 Mb TDR内鉴定出4个LCR。尽管LCR在共享模块的内容和组织上不同，但它们之间共有的那些模块彼此共享97-98%的序列同一性。通过荧光原位杂交（FISH）分析，发现4个22q11.2缺失突变的终点均位于LCRs上。脉冲场凝胶电泳和Southern杂交检测了3个22q11.2缺失突变的重排连接片段。通过PCR和PCR产物测序分析连接片段，表明LCR直接参与22q11.2缺失的形成。22号染色体上重复的进化起源已经通过非人灵长类动物的FISH分析进行了评估。旧大陆猴子身上的多重信号表明，复制事件可能至少发生在2000万至2500万年前。
The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial syndromes (DGS/VCFS), is the most common microdeletion syndrome. The majority of deleted patients share a common 3 Nib hemizygous deletion of 22q11.2. The remaining patients include those who have smaller deletions that are nested within the 3 Mb typically deleted region (TDR) and a few with rare deletions that have no overlap with the TDR. The identification of chromosome 22-specific duplicated sequences or low copy repeats (LCRs) near the end-points of the 3 Mb TDR has led to the hypothesis that they mediate deletions of 22q11.2. The entire 3 Mb TDR has been sequenced, permitting detailed investigation of the LCRs and their involvement in the 22q11.2 deletions. Sequence analysis has identified four LCRs within the 3 Mb TDR. Although the LCRs differ in content and organization of shared modules, those modules that are common between them share 97-98% sequence identity with one another. By fluorescence in situ hybridization (FISH) analysis, the end-points of four variant 22q11.2 deletions appear to localize to the LCRs, Pulsed-field gel electrophoresis and Southern hybridization have been used to identify rearranged junction fragments from three variant deletions. Analysis of junction fragments by PCR and sequencing of the PCR products implicate the LCRs directly in the formation of 22q11.2 deletions. The evolutionary origin of the duplications on chromosome 22 has been assessed by FISH analysis of non-human primates. Multiple signals in Old World monkeys suggest that the duplication events may have occurred at least 20-25 million years ago.