Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation

The chicken coloboma mutation exhibits features similar to human congenital developmental malformations such as ocular coloboma, cleft-palate, dwarfism, and polydactyly. The coloboma-associated region and encoded genes were investigated using advanced genomic, genetic, and gene expression technologies. Initially, the mutation was linked to a 990 kb region encoding 11 genes; the application of the genetic and genomic tools led to a reduction of the linked region to 176 kb and the elimination of 7 genes. Furthermore, bioinformatics analyses of capture array-next generation sequence data identified genetic elements including SNPs, insertions, deletions, gaps, chromosomal rearrangements, and miRNA binding sites within the introgressed causative region relative to the reference genome sequence. Coloboma-specific variants within exons, UTRs, and splice sites were studied for their contribution to the mutant phenotype. Our compiled results suggest three genes for future studies. The three candidate genes, SLC30A5 (a zinc transporter), CENPH (a centromere protein), and CDK7 (a cyclin-dependent kinase), are differentially expressed (compared to normal embryos) at stages and in tissues affected by the coloboma mutation. Of these genes, two (SLC30A5 and CENPH) are considered high-priority candidate based upon studies in other vertebrate model systems. Citation: Robb EA, Antin PB, Delany ME (2013) Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation. PLoS ONE 8(4): e60267. doi:10.1371/journal.pone.0060267 Editor: Laszlo Orban, Temasek Life Sciences Laboratory, Singapore Received March 24, 2012; Accepted February 26, 2013; Published April 9, 2013 Copyright: 2013 Robb et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Research was supported by the U.S. Department of Agriculture-National Institute of Food and Agriculture Multistate Research NC-1170 (CA-D*-ASC6414-RR), the NRSP-8 National Animal Genome Research Support Program (CA-D*-ASC-7233-RR) and the UC Davis (UCD) John and Joan Fiddyment endowment (M.E.D.). The WEisH studies were supported by National Institutes of Health grant HD064559 (P.B.A.). The authors gratefully acknowledge the UCD Department of Animal Science for graduate student fellowship support and the UCD Jastro-Shields Graduate Research Award (E.A.R.). The authors appreciate the infrastructure and the poultry genetic resources supported by the UCD Department of Animal Science, College of Agricultural and Environmental Sciences, and the California Agricultural Experiment Station. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]