Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
PLoS One. 2011;6(5):e14814. doi: 10.1371/journal.pone.0014814. Epub 2011 May 26.
Due to the increased accuracy of Copy Number Variable region (CNV) break point mapping, it is now possible to say with a reasonable degree of confidence whether a gene (i) falls entirely within a CNV; (ii) overlaps the CNV or (iii) actually contains the CNV. We classify these as type I, II and III CNV genes respectively.
Here we show that although type I genes vary in copy number along with the CNV, most of these type I genes have the same expression levels as wild type copy numbers of the gene. These genes must, therefore, be under homeostatic dosage compensation control. Looking into possible mechanisms for the regulation of gene expression we found that type I genes have a significant paucity of genes regulated by miRNAs and are not significantly enriched for monoallelically expressed genes. Type III genes, on the other hand, have a significant excess of genes regulated by miRNAs and are enriched for genes that are monoallelically expressed.
Many diseases and genomic disorders are associated with CNVs so a better understanding of the different ways genes are associated with normal CNVs will help focus on candidate genes in genome wide association studies.
由于拷贝数可变区 (CNV) 断裂点映射的准确性提高，现在可以相当有把握地说，一个基因 (i) 是否完全在 CNV 内；(ii) 与 CNV 重叠；或 (iii) 实际上包含 CNV。我们分别将这些归类为 I 型、II 型和 III 型 CNV 基因。
在这里，我们表明，尽管 I 型基因的拷贝数随 CNV 而变化，但这些 I 型基因中的大多数与该基因的野生型拷贝数具有相同的表达水平。因此，这些基因必须受到同源剂量补偿控制。在研究基因表达调控的可能机制时，我们发现 I 型基因受 miRNA 调控的基因明显较少，并且单等位基因表达的基因不显著富集。另一方面，III 型基因受 miRNA 调控的基因明显较多，并且富含单等位基因表达的基因。
许多疾病和基因组紊乱都与 CNV 有关，因此，更好地了解基因与正常 CNV 的不同关联方式将有助于在全基因组关联研究中关注候选基因。
