Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters.

Diana Hernandez, Azara Janmohamed, Pritpal Chandan, Ian R Phillips, Elizabeth A Shephard
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引用次数: 159

Abstract

Objectives: To date, six flavin-containing monooxygenase (FMO) genes have been identified in humans, FMOs 1, 2, 3, 4 and 6, which are located within a cluster on chromosome 1, and FMO5, which is located outside the cluster. The objectives were to review and update current knowledge of the structure and expression profiles of these genes and of their mouse counterparts and to determine, via a bioinformatics approach, whether other FMO genes are present in the human and mouse genomes.

Results and conclusions: We have identified, for the first time, a mouse Fmo6 gene. In addition, we describe a novel human FMO gene cluster on chromosome 1, located 4 Mb telomeric of the original cluster. The novel cluster contains five genes, all of which exhibit characteristics of pseudogenes. We propose the names FMO 7P, 8P, 9P, 10P and 11P for these genes. We also describe a novel mouse gene cluster, located approximately 3.5 Mb distal of the original gene cluster on Chromosome 1. The novel mouse cluster contains three genes, all of which contain full-length open-reading frames and possess no obvious features characteristic of pseudogenes. One of the genes is apparently a functional orthologue of human FMO9P. We propose the names Fmo9, 12 and 13 for the novel mouse genes. Orthologues of these genes are also present in rat. Sequence comparisons and phylogenetic analyses indicate that the novel human and mouse gene clusters arose, not from duplications of the known gene cluster, but via a series of independent gene duplication events. The mammalian FMO gene family is thus more complex than previously realised.

人和小鼠含黄素单加氧酶基因的组织和进化:新基因和假基因簇的鉴定。
目的:迄今为止,已在人类中鉴定出6个含黄素单加氧酶(FMO)基因,fmo1、2、3、4和6位于1号染色体上的一个簇内,FMO5位于簇外。目的是回顾和更新这些基因及其小鼠对应基因的结构和表达谱的现有知识,并通过生物信息学方法确定人类和小鼠基因组中是否存在其他FMO基因。结果和结论:我们首次鉴定出小鼠Fmo6基因。此外,我们在1号染色体上描述了一个新的人类FMO基因簇,位于原簇的4 Mb端粒上。该簇包含5个基因,它们都具有假基因的特征。我们建议将这些基因命名为FMO 7P、8P、9P、10P和11P。我们还描述了一个新的小鼠基因簇,位于1号染色体上原始基因簇的远端约3.5 Mb。该小鼠簇包含3个基因,均包含全长开放阅读框,不具有明显的假基因特征。其中一个基因显然是人类FMO9P的功能同源物。我们建议将这些新的小鼠基因命名为Fmo9、12和13。这些基因的同源物也存在于大鼠中。序列比较和系统发育分析表明,新的人类和小鼠基因簇不是由已知基因簇的重复产生的,而是通过一系列独立的基因重复事件产生的。因此,哺乳动物FMO基因家族比以前认识到的要复杂得多。
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