title: Isolation and characterization of a human chromosome 21q22.3 gene (WDR4) and its mouse homologue that code for a WD-repeat protein.
abstract: To identify candidate genes for Down syndrome phenotypes or disorders that map to human chromosome 21q22.3, trapped exons are being used to isolate full-length transcripts. We isolated a full-length cDNA (WDR4) encoding a novel WD-repeat protein and its mouse homologue. Two RNA species of 1.5 and 2.1 kb were observed in human, with the 1.5-kb transcript being produced by a splicing event after the stop codon, and thus both transcripts encode the same putative 412-amino-acid protein containing four guanine nucleotide-binding WD repeats. The more highly expressed 1.5-kb transcript was expressed mainly in fetal tissues while the 2.1-kb transcript showed a faint expression in most tissues. Two additional alternative splicing events of 270 and 52 nt within the coding region were observed. The WDR4 gene spans 37 kb and is divided into 11 coding exons. WDR4 maps between PDE9A and NDUFV3, a region where several genetic disorders, including a form of manic-depressive psychosis, also map, and seven sequence variants observed in the WDR4 gene could be used in association studies.
authors.affiliation: Division of Medical Genetics, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Michaud
authors.forename: J
authors.initials: J
authors.lastname: Kudoh
authors.forename: A
authors.initials: A
authors.lastname: Berry
authors.forename: B
authors.initials: B
authors.lastname: Bonne-Tamir
authors.forename: M D
authors.initials: MD
authors.lastname: Lalioti
authors.forename: C
authors.initials: C
authors.lastname: Rossier
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.forename: K
authors.initials: K
authors.lastname: Kawasaki
authors.forename: S
authors.initials: S
authors.lastname: Asakawa
authors.forename: S
authors.initials: S
authors.lastname: Minoshima
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: H S
authors.initials: HS
authors.lastname: Scott
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D003638:Deafness / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; C417912:WDR4 protein, human; D004247:DNA; D019204:GTP-Binding Proteins; C000608107:WDR4 protein, mouse