title: Genomic organization and expression profile of the human and mouse WAVE gene family.
abstract: The WAVE gene family, which contains three members, has been shown to play a major role in the actin polymerization and cytoskeleton organization processes. We have identified the WAVE3 gene from Chromosome (Chr) 13q12, as being involved in one of the breakpoints of a t(1:13)(q21:q12) reciprocal translocation, in a patient with ganglioneuroblastoma (Sossey-Alaoui et al. 2002; Oncogene 21: 5967-5974). We have also reported the cloning of the mouse Wave3. During our analysis of the human gene map, we also noted that WAVE2 maps to Chr region lp35-36, which frequently undergoes loss of heterozygosity and deletion in advanced stage neuroblastoma. These data clearly indicate a possible involvement of the WAVE genes in the pathogenesis of neuroblastoma. In this study, we report the complete genomic organization and expression profile of the three human WAVE genes and their mouse orthologs. We show that the WAVE genes have distinctive expression patterns in both adult and fetal human and mouse tissues. We also show a high level of conservation between these genes, in both the nucleotide and protein sequences. We finally show that the genomic structure is highly conserved among these genes and that the mouse Wave genes map to chromosome regions that have synteny in the human genome. The gene content in these syntenic regions is also conserved, suggesting that the WAVE genes are derived from a common ancient ancestor by genome duplication. The genomic characterization and expression analysis of the WAVE genes provide the basis towards understanding the function of these genes. It also provides the first steps towards the development of mouse models for the role of the WAVE genes in actin and cytoskeleton organization in general, and in the development of neuroblastoma in particular.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, 110 C&V Building, Elm and Carlton Streets, Buffalo, New York 14263, USA. khalid.sossey-alaoui@roswellpark.org
authors.forename: Khalid
authors.initials: K
authors.lastname: Sossey-Alaoui
authors.forename: Karen
authors.initials: K
authors.lastname: Head
authors.forename: Norma
authors.initials: N
authors.lastname: Nowak
authors.forename: John K
authors.initials: JK
authors.lastname: Cowell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007438:Introns; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D051300:Wiskott-Aldrich Syndrome Protein Family
chemical_list: D017931:DNA Primers; D008840:Microfilament Proteins; C120152:WASF2 protein, human; C120153:WASF3 protein, human; C495774:Wasf1 protein, mouse; C492303:Wasf2 protein, mouse; C485623:Wasf3 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family