Dermitzakis Emmanouil T, Reymond Alexandre, Lyle Robert, Scamuffa Nathalie, Ucla Catherine, Deutsch Samuel, Stevenson Brian J, Flegel Volker, Bucher Philipp, Jongeneel C Victor, Antonarakis Stylianos E
Division of Medical Genetics, 1 Rue Michel-Servet, University of Geneva Medical School and University Hospitals of Geneva, CH-1211 Geneva, Switzerland.
Nature. 2002 Dec 5;420(6915):578-82. doi: 10.1038/nature01251.
The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.
利用比较基因组学推断基因组功能，依赖于对基因组不同组成部分在进化时间里如何变化的理解。此类比较分析的目的是识别保守的、功能转录序列，如蛋白质编码基因和非编码RNA基因，以及其他功能序列，如调控区域，还有其他基因组特征。在此，我们已将整个人类21号染色体与小鼠基因组的同区域进行了比较，并识别出大量功能未知的保守片段。尽管先前的研究也有类似发现，但这些保守序列是否为基因尚不清楚。在此，我们对人类21号染色体进行了广泛的实验和计算分析，以便为人类21号染色体（参考文献8）和同区域小鼠区域之间保守的序列赋予功能。我们的数据支持大量潜在功能性非基因序列的存在，可能是调控性和结构性的。将人类21号染色体保守成分的特性与该染色体快速积累的功能数据相结合，将极大地增进我们对序列保守性在哺乳动物基因组中作用的理解。
