Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes
Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes
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DOI：
10.1186/gb-2007-8-6-r114
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发表时间：
2007-01-01
期刊：
影响因子：
12.3
通讯作者：
Flomen, Rachel H.
中科院分区：
文献类型：
--
作者：
Makoff, Andrew J.;Flomen, Rachel H.
背景：15号染色体包含许多节段性重复，其中包括15q11-q13的一些片段重复，这些片段似乎与导致Prader-Willi综合征和Angelman综合征以及其他基因组疾病的缺失有关。当前版本的人类基因组序列是不完整的，在15q的近端区域有七个缺口，其中一些是重复序列。我们通过对公共数据库中测序的基因组克隆进行详细的检查来研究这一区域，重点是来自RP11文库的来自一个个体的克隆。结果：我们的分析发现了组装错误，包括重叠群NT_078094方向错误，并使重叠群之间的大部分间隙得以弥合。我们已经构建了一张地图，其中分段复制不再被间隙打断，并且共同揭示了一个复杂的区域。有两对大的直接重复序列位于与Prader-Willi和Angelman综合征相关的两类缺失区域。也有大的反向重复序列，它解释了观察到的含有15q近端两个拷贝的额外标记染色体的形成，并与自闭症谱系障碍有关，当涉及母系起源的复制时(inv dup[15]综合征)。结论：我们制作了15q11-q14的片段图，揭示了几个大的直接和反向重复序列，这些大的正向和反向重复序列在当前人类基因组序列上是不完全和不准确的。其中一些重复显然是已知基因组疾病的缺失和复制的原因，而一些可能增加对其他疾病的易感性。
Background: Chromosome 15 contains many segmental duplications, including some at 15q11-q13 that appear to be responsible for the deletions that cause Prader-Willi and Angelman syndromes and for other genomic disorders. The current version of the human genome sequence is incomplete, with seven gaps in the proximal region of 15q, some of which are flanked by duplicated sequence. We have investigated this region by conducting a detailed examination of the sequenced genomic clones in the public database, focusing on clones from the RP11 library that originates from one individual.Results: Our analysis has revealed assembly errors, including contig NT_078094 being in the wrong orientation, and has enabled most of the gaps between contigs to be closed. We have constructed a map in which segmental duplications are no longer interrupted by gaps and which together reveals a complex region. There are two pairs of large direct repeats that are located in regions consistent with the two classes of deletions associated with Prader-Willi and Angelman syndromes. There are also large inverted repeats that account for the formation of the observed supernumerary marker chromosomes containing two copies of the proximal end of 15q and associated with autism spectrum disorders when involving duplications of maternal origin ( inv dup[ 15] syndrome).Conclusion: We have produced a segmental map of 15q11-q14 that reveals several large direct and inverted repeats that are incompletely and inaccurately represented on the current human genome sequence. Some of these repeats are clearly responsible for deletions and duplications in known genomic disorders, whereas some may increase susceptibility to other disorders.