Department of Molecular Biology, Umeå University, SE-90187 Umeå, Sweden.
Nucleic Acids Res. 2012 Jul;40(13):5926-37. doi: 10.1093/nar/gks245. Epub 2012 Mar 19.
Variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segments (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined; it is the leading cause of miscarriages and mental retardation and a hallmark of cancer. However, despite their documented importance in disease, the effects of aneuploidies on the transcriptome remain largely unknown. We have examined the expression effects of seven heterozygous chromosomal deficiencies, both singly and in all pairwise combinations, in Drosophila melanogaster. The results show that genes in one copy are buffered, i.e. expressed more strongly than the expected 50% of wild-type level, the buffering is general and not influenced by other monosomic regions. Furthermore, long genes are significantly more highly buffered than short genes and gene length appears to be the primary determinant of the buffering degree. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Thus, enhanced proteolysis appears to be a general response to aneuploidy.
个体染色体数量的变化（染色体非整倍性）或染色体片段（片段非整倍性）与所有被研究物种的发育异常和适应能力下降有关；它是流产和智力迟钝的主要原因，也是癌症的标志。然而，尽管它们在疾病中的重要性已被记录在案，但非整倍体对转录组的影响在很大程度上仍不清楚。我们已经在果蝇中检查了七种杂合性染色体缺失的表达效应，包括单独缺失和所有两两组合缺失的情况。结果表明，一份拷贝中的基因受到缓冲，即表达强度高于野生型水平的 50%，这种缓冲是普遍的，不受其他单体区域的影响。此外，长基因比短基因的缓冲程度明显更高，并且基因长度似乎是缓冲程度的主要决定因素。对于短基因，缓冲的程度取决于表达水平和表达模式。此外，结果表明，在缺失杂合体中，参与蛋白水解的基因的表达增强，并且与缓冲的程度呈负相关。因此，增强的蛋白水解似乎是对非整倍体的普遍反应。
