Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation

Elizabeth A. Robb, Parker B Antin, Mary E. Delany

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere60267
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 9 2013

Fingerprint

Coloboma
Genes
mutation
Mutation
genes
cleft palate
Untranslated Regions
Polydactyly
genomics
Dwarfism
cyclin-dependent kinase
Cyclin-Dependent Kinases
dwarfing
Centromere
centromeres
Cleft Palate
Computational Biology
MicroRNAs
microRNA
bioinformatics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation. / Robb, Elizabeth A.; Antin, Parker B; Delany, Mary E.

In: PLoS One, Vol. 8, No. 4, e60267, 09.04.2013.

Research output: Contribution to journalArticle

Robb, Elizabeth A. ; Antin, Parker B ; Delany, Mary E. / Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation. In: PLoS One. 2013 ; Vol. 8, No. 4.
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