Journal article
Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18
eLife, Vol.9, e51325
02/07/2020
DOI: 10.7554/eLife.51325
PMCID: PMC7039683
PMID: 32031521
Abstract
Genome-wide association studies for non-syndromic orofacial clefting (OFC) have identified single nucleotide polymorphisms (SNPs) at loci where the presumed risk-relevant gene is expressed in oral periderm. The functional subsets of such SNPs are difficult to predict because the sequence underpinnings of periderm enhancers are unknown. We applied ATAC-seq to models of human palate periderm, including zebrafish periderm, mouse embryonic palate epithelia, and a human oral epithelium cell line, and to complementary mesenchymal cell types. We identified sets of enhancers specific to the epithelial cells and trained gapped-kmer support-vector-machine classifiers on these sets. We used the classifiers to predict the effects of 14 OFC-associated SNPs at 12q13 near
. All the classifiers picked the same SNP as having the strongest effect, but the significance was highest with the classifier trained on zebrafish periderm. Reporter and deletion analyses support this SNP as lying within a periderm enhancer regulating
/
expression.
Details
- Title: Subtitle
- Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18
- Creators
- Huan Liu - Department of Periodontology, School of Stomatology, Wuhan University, Wuhan, ChinaKaylia Duncan - Interdisciplinary Program in Molecular Medicine, University of Iowa, Iowa City, United StatesAnnika Helverson - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, United StatesPriyanka Kumari - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, United StatesCamille Mumm - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, United StatesYao Xiao - State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaJenna Colavincenzo Carlson - Department of Biostatistics, University of Pittsburgh, Pittsburgh, United StatesFabrice Darbellay - Environmental Genomics and Systems Biology Division, Lawrence Berkeley Laboratories, Berkeley, United StatesAxel Visel - University of California, Merced, Merced, United StatesElizabeth Leslie - Department of Human Genetics, Emory University School of Medicine, Atlanta, GeorgiaPatrick Breheny - Department of Biostatistics, University of Iowa, Iowa City, United StatesAlbert J Erives - Department of Biology, University of Iowa, Iowa City, United StatesRobert A Cornell - Interdisciplinary Program in Molecular Medicine, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.9, e51325
- DOI
- 10.7554/eLife.51325
- PMID
- 32031521
- PMCID
- PMC7039683
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- R01 DE023575 / NIDCR NIH HHS 2017CFB515 / Natural Science Foundation of Hubei Province 81771057 / National Natural Science Foundation of China R01 DE027362 / NIDCR NIH HHS R01 DE028599 / NIDCR NIH HHS R00 DE025060 / NIDCR NIH HHS 81400477 / National Natural Science Foundation of China U01 DE024427 / NIDCR NIH HHS K99 DE025060 / NIDCR NIH HHS P30 CA086862 / NCI NIH HHS R56 DE023575 / NIDCR NIH HHS
- Language
- English
- Date published
- 02/07/2020
- Academic Unit
- Anatomy and Cell Biology; Biostatistics; Biology; Internal Medicine
- Record Identifier
- 9984217429502771
Metrics
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