title: Strong conservation of the human NF2 locus based on sequence comparison in five species.
abstract: We analyzed 137 kb covering human neurofibromatosis 2 ( NF2) tumor suppressor locus and orthologous loci from baboon, mouse, rat, and pufferfish Takifugu rubripes. A predominant feature of human-rodent conservation is a very similar distribution of conserved islands, regarding length, position, and degree of identity. By use of a threshold of 75% identity over > or =100 bp of gap-free alignment, comparisons of human-mouse sequences resulted in 3.58% for extra-exonic conservation, which can be compared to 4.5% of exonic sequence content within the human locus. We identified a duplication of neurofibromin 2 in pufferfish, which resulted in two putative proteins with 74% and 76% identity to the human protein. One distinct island (called inter 1), conserved between all analyzed species, was located between promoters of the NIPSNAP1 and NF2 genes. Inter 1 might represent a novel regulatory element, important for the function of this locus. The high level of intronic conservation in the NF2 locus suggests that a number of unknown regulatory elements might exist within this gene. These elements could be affected by disease-causing mutations in NF2 patients and NF2-associated tumors. Alternatively, this conservation might be explained by presence of not yet characterized transcriptional unit(s) within this locus.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, 3rd floor, Dag Hammarskjöds väg 20, Uppsala University, 751 85 Uppsala, Sweden.
authors.forename: Caisa M
authors.initials: CM
authors.lastname: Hansson
authors.forename: Haider
authors.initials: H
authors.lastname: Ali
authors.forename: Carl E G
authors.initials: CE
authors.lastname: Bruder
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Fransson
authors.forename: Sindy
authors.initials: S
authors.lastname: Kluge
authors.forename: Björn
authors.initials: B
authors.lastname: Andersson
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Roe
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D017124:Conserved Sequence / Q000235:genetics*; D020440:Gene Duplication; D015723:Gene Library; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008322:Mammals / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011506:Proteins / Q000235:genetics; D016415:Sequence Alignment; D017385:Sequence Homology; D023741:Takifugu / Q000235:genetics*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C113197:NIPSNAP1 protein, human; D011506:Proteins