RT Journal Article
SR Electronic
T1 Tyr is Responsible for the Cctq1a QTL and Links Developmental Environment to Central Corneal Thickness Determination
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.22.461410
DO 10.1101/2021.09.22.461410
A1 Kacie J. Meyer
A1 Demelza R. Larson
A1 S. Scott Whitmore
A1 Carly J. van der Heide
A1 Adam Hedberg-Buenz
A1 Laura M. Dutca
A1 Swanand Koli
A1 Nicholas Pomernackas
A1 Hannah E. Mercer
A1 Maurisa N. Mansaray
A1 William J. Paradee
A1 Kai Wang
A1 K. Saidas Nair
A1 Todd E. Scheetz
A1 Michael G. Anderson
YR 2021
UL http://biorxiv.org/content/early/2021/11/11/2021.09.22.461410.abstract
AB Central corneal thickness is a quantitative trait with important associations to human health. In a phenotype-driven approach studying corneal thickness of congenic derivatives of C57BLKS/J and SJL/J mice, the critical region for a quantitative trait locus influencing corneal thickness, Cctq1a, was delimited to a 10-gene interval. Exome sequencing, RNAseq, and studying independent mutations eliminated multiple candidate genes and confirmed one. Though the causative gene, Tyr, has no obvious direct function in the transparent cornea, studies with multiple alleles on matched genetic backgrounds, both in isolation and genetic complementation crosses, confirmed allelism of Tyr-Cctq1a; albino mice lacking Tyr function had thin corneas. Albino mice also had increased axial length. Because albinism exposes eyes to increased light, the effect of dark-rearing was tested and found to rescue central corneal thickness. In sum, the results point to an epiphenomenon; developmental light exposure interacts with genotype as an important determinate of adult corneal thickness.Competing Interest StatementThe authors have declared no competing interest.