In Vitro Human Keratinocyte Migration Rates Are Associated with SNPs in the KRT1 Interval
Open Access
- 1 August 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 2 (8), e697
- https://doi.org/10.1371/journal.pone.0000697
Abstract
Efforts to develop effective therapeutic treatments for promoting fast wound healing after injury to the epidermis are hindered by a lack of understanding of the factors involved. Re-epithelialization is an essential step of wound healing involving the migration of epidermal keratinocytes over the wound site. Here, we examine genetic variants in the keratin-1 (KRT1) locus for association with migration rates of human epidermal keratinocytes (HEK) isolated from different individuals. Although the role of intermediate filament genes, including KRT1, in wound activated keratinocytes is well established, this is the first study to examine if genetic variants in humans contribute to differences in the migration rates of these cells. Using an in vitro scratch wound assay we observe quantifiable variation in HEK migration rates in two independent sets of samples; 24 samples in the first set and 17 samples in the second set. We analyze genetic variants in the KRT1 interval and identify SNPs significantly associated with HEK migration rates in both samples sets. Additionally, we show in the first set of samples that the average migration rate of HEK cells homozygous for one common haplotype pattern in the KRT1 interval is significantly faster than that of HEK cells homozygous for a second common haplotype pattern. Our study demonstrates that genetic variants in the KRT1 interval contribute to quantifiable differences in the migration rates of keratinocytes isolated from different individuals. Furthermore we show that in vitro cell assays can successfully be used to deconstruct complex traits into simple biological model systems for genetic association studies.Keywords
This publication has 30 references indexed in Scilit:
- Allele-Specific KRT1 Expression Is a Complex TraitPLoS Genetics, 2006
- Cis - and Trans -Acting Gene Regulation Is Associated with OsteoarthritisAmerican Journal of Human Genetics, 2006
- Analysis of allelic differential expression in human white blood cellsGenome Research, 2006
- New quantitative trait loci that regulate wound healing in an intercross progeny from DBA/1J and 129×1/SvJ inbred strains of miceFunctional & Integrative Genomics, 2005
- Characterization of New Members of the Human Type II Keratin Gene Family and a General Evaluation of the Keratin Gene Domain on Chromosome 12q13.13Journal of Investigative Dermatology, 2005
- Identification of Wound Healing/Regeneration Quantitative Trait Loci (QTL) at Multiple Time Points that Explain Seventy Percent of Variance in (MRL/MpJ and SJL/J) Mice F2 PopulationGenome Research, 2001
- The epidermis: rising to the surfaceCurrent Opinion in Genetics & Development, 1994
- Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro.The Journal of cell biology, 1989
- Sequence complexity of nuclear and messenger RNA in HeLa cellsJournal of Molecular Biology, 1980
- Stability of nuclear RNA in mammalian cellsJournal of Molecular Biology, 1974