Comparative sequence analysis of 634 kb of the mouse chromosome 16 region of conserved synteny with the human velocardiofacial syndrome region on chromosome 22q11.2.
Comparative sequence analysis of 634 kb of the mouse chromosome 16 region of conserved synteny with the human velocardiofacial syndrome region on chromosome 22q11.2.
复制标题
对小鼠 16 号染色体 634 kb 的保守同线性区域与人类 22q11.2 号染色体上的颊心面综合征区域进行比较序列分析。
DOI：
10.1006/geno.1999.6044
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Reeves,RH
中科院分区：
文献类型：
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作者：
Lund,J;Chen,F;Hua,A;Roe,B;Budarf,M;Emanuel,BS;Reeves,RH
将小鼠近端 16 号染色体上延伸 634 kb 的小鼠基因组 DNA 序列与来自染色体 22q11.2 的相应人类序列进行比较。该区域的单倍体不足会导致人类腭心面综合征（VCFS）。相对于人类，小鼠区域被重新排列成三个保守的区块，但基因内容和位置在这些区块内高度保守。对这些块之一的边界的检查表明，进化染色体重排发生在小鼠谱系中，导致 ZNF74 的小鼠直系同源物失活。序列分析鉴定出 21 个基因和 15 个 EST。其中包括 2 个新基因 Srec2 和 Cals2，以及先前未描述的其他几个基因的剪接变体。使用 GRAIL2、MZEF 或对 491 kb 的小鼠和人类保守序列进行比较分析来发现外显子。序列比较非常有效，可以识别每个基因和几乎每个外显子，而不会出现单独使用算法方法时出现的高频率假阳性预测。结合起来，这些程序识别出了每个基因，没有出现假阳性预测。比较序列分析还揭示了非编码序列中广泛保守的区域，占序列的 6%。已经建立了此类序列的文库，以形成调节和结构元件的一般研究的资源。
Mouse genomic DNA sequence extending 634 kb on proximal mouse chromosome 16 was compared to the corresponding human sequence from chromosome 22q11.2. Haploinsufficiency for this region results in velocardiofacial syndrome (VCFS) in humans. The mouse region is rearranged into three conserved blocks relative to human, but gene content and position are highly conserved within these blocks. Examination of the boundaries of one of these blocks suggested that the evolutionary chromosomal rearrangement occurred in the mouse lineage, resulting in inactivation of the mouse orthologue of ZNF74. Sequence analysis identified 21 genes and 15 ESTs. These include 2 novel genes, Srec2 and Cals2, and previously undescribed splice variants of several other genes. Exon discovery was carried out using GRAIL2, MZEF, or comparative analysis across 491 kb of conserved mouse and human sequence. Sequence comparison was highly effective, identifying every gene and nearly every exon without the high frequency of false-positive predictions seen when algorithmic methods were used alone. In combination, these procedures identified every gene with no false-positive predictions. Comparative sequence analysis also revealed regions of extensive conservation among noncoding sequences, accounting for 6% of the sequence. A library of such sequences has been established to form a resource for generalized studies of regulatory and structural elements.