Genetic associations and phenotypic heterogeneity in the craniosynostotic rabbit

James R Gilbert, Joseph E Losee, Mark P Mooney, James J Cray, Jennifer Gustafson, Michael L Cunningham and Gregory M Cooper

PLOS ONE, 2018, vol. 13, issue 9, 1-14

Abstract: Craniosynostosis (CS) is a disorder that involves the premature ossification of one or more cranial sutures. Our research team has described a naturally occurring rabbit model of CS with a variable phenotype and unknown etiology. Restriction-site associated DNA (RAD) sequencing is a genomic sampling method for identifying genetic variants in species with little or no existing sequence data. RAD sequencing data was analyzed using a mixed linear model to identify single nucleotide polymorphisms (SNPs) associated with disease occurrence and onset in the rabbit model of CS. SNPs achieving a genome-wide significance of p ≤ 5 x 10−8 were identified on chromosome 2 in association with disease occurrence and on chromosomes 14 and 19 in association with disease onset. Genotyping identified a coding variant in fibroblast growth factor binding protein 1 (FGFBP-1) on chromosome 2 and a non-coding variant upstream of integrin alpha 3 (ITGA3) on chromosome 19 that associated with disease occurrence and onset, respectively. Retrospective analysis of patient data revealed a significant inverse correlation between FGFBP-1 and ITGA3 transcript levels in patients with coronal CS. FGFBP-1 and ITGA3 are genes with roles in early development that warrant functional study to further understand suture biology.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0204086

DOI: 10.1371/journal.pone.0204086

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