title: Characterization of a novel gene adjacent to PAX6, revealing synteny conservation with functional significance.
abstract: The human eye anomaly aniridia is normally caused by intragenic mutations of PAX6. Several cases of aniridia are, however, associated with chromosomal rearrangements that leave the PAX6 gene intact. We have identified and characterized a novel gene, PAXNEB (C11orf19), downstream (telomeric) of PAX6. Sequence analysis, including interspecies comparisons, show this gene to consist of 10 exons, with an unusually large final intron spanning 134 kb in human and 18 kb in Fugu. This intron is disrupted by each chromosomal rearrangement. The 2-kb PAXNEB transcript, encoding a 424-amino acid protein, is expressed in all cell lines tested. The homologous mouse cDNA is broadly expressed in mouse embryos. PAXNEB is highly conserved from mammals to fish, with some regions of the protein showing conservation to invertebrates, yeast, and plants. The possible role of PAXNEB in aniridia was assessed. Using a transgenic mouse model, we show that the aniridia phenotype of the chromosomal rearrangement cases is not due to the heterozygous loss of PAXNEB function.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. d.kleinjan@hgu.mrc.ac.uk
authors.forename: Dirk A
authors.initials: DA
authors.lastname: Kleinjan
authors.forename: Anne
authors.initials: A
authors.lastname: Seawright
authors.forename: Greg
authors.initials: G
authors.lastname: Elgar
authors.forename: Veronica
authors.initials: V
authors.lastname: van Heyningen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015783:Aniridia / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D005136:Eye Proteins; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D026801:Synteny
chemical_list: C456976:ELP4 protein, human; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins