Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

• DOI: 10.1186/s11689-015-9113-x
• Publication Date: 2015-06-11T05:40:11Z
• Authors: Alina Guna; Nancy J. Butcher; Anne S. Bassett
• Keywords: Model Organism; Synteny

22q11.2 deletion syndrome (22q11.2DS) is the most common micro-deletion syndrome. The associated conveys strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful determining role of some genes overlapped by hemizygous phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited exploring these genotype-phenotype relationships.We first developed a comprehensive map human region, delineating gene content, brain expression. To identify putative orthologs, standard methods were used to interrogate proteomes zebrafish (D. rerio), fruit fly melanogaster), worm (C. elegans), addition mouse. Spatial locations conserved homologues mapped examine syntenic relationships. We systematically cataloged available knockout knockdown all across organisms, review phenotypes.There 90 typical 2.5 Mb region. Of 46 protein-coding genes, 41 (89.1 %) documented expression brain. Identified (n = 37, 80.4 comparable those 40, 86.9 included cluster structures. There 22 (47.8 17 (37.0 involving multiple chromosomes. Individual mutants simple but not Although data relatively limited species, there was evidence roles neurodevelopmental four six mitochondrial region.Simple represent powerful underutilized means investigating mechanisms underlying elevated disorders 22q11.2DS. This comparative multi-species study provides novel resources support potential utility non-mouse studies high-throughput drug screening. approach has implications other recurrent copy number variations with phenotypes.