Centre de Recherche de Ste-Justine, 3175, Côte Ste-Catherine, Montréal QC H3T 1C5, Canada.
Curr Genomics. 2010 Nov;11(7):482-99. doi: 10.2174/138920210793175886.
The phenome is the complete set of phenotypes resulting from genetic variation in populations of an organism. Saturation of a phenome implies the identification and phenotypic description of mutations in all genes in an organism, potentially constrained to those encoding proteins. The human genome is believed to contain 20-25,000 protein coding genes, but only a small fraction of these have documented mutant phenotypes, thus the human phenome is far from complete. In model organisms, genetic saturation entails the identification of multiple mutant alleles of a gene or locus, allowing a consistent description of mutational phenotypes for that gene. Saturation of several model organisms has been attempted, usually by targeting annotated coding genes with insertional transposons (Drosophila melanogaster, Mus musculus) or by sequence directed deletion (Saccharomyces cerevisiae) or using libraries of antisense oligonucleotide probes injected directly into animals (Caenorhabditis elegans, Danio rerio). This paper reviews the general state of the human phenome, and discusses theoretical and practical considerations toward a saturation analysis in humans. Throughout, emphasis is placed on high penetrance genetic variation, of the kind typically asociated with monogenic versus complex traits.
表型是生物体群体中遗传变异所产生的完整表型集合。表型的饱和意味着鉴定和描述生物体中所有基因的突变，可能仅限于那些编码蛋白质的基因。人类基因组被认为包含 20-25000 个蛋白质编码基因，但只有一小部分具有有文献记载的突变表型，因此人类表型远未完全确定。在模式生物中，遗传饱和需要鉴定一个基因或基因座的多个突变等位基因，从而能够对该基因的突变表型进行一致的描述。已经尝试了几种模式生物的饱和，通常是通过用插入转座子（黑腹果蝇、小家鼠）或序列定向缺失（酿酒酵母）靶向注释编码基因，或使用直接注射到动物体内的反义寡核苷酸探针文库（秀丽隐杆线虫、斑马鱼）。本文综述了人类表型的总体状况，并讨论了在人类中进行饱和分析的理论和实际考虑因素。全文强调了高外显率遗传变异，这种变异通常与单基因性状和复杂性状有关。
