Analysis of Zebrafish Periderm Enhancers Facilitates Identification of a Regulatory Variant Near Human

Overview

Journal Elife

Specialty Biology

Date 2020 Feb 8

PMID 32031521

Citations 21

Authors

Huan Liu

Kaylia Duncan

Annika Helverson

Priyanka Kumari

Camille Mumm

Yao Xiao

Jenna Colavincenzo Carlson

Fabrice Darbellay

Axel Visel

Elizabeth Leslie

Patrick Breheny

Albert J Erives

Robert A Cornell

Affiliations

Soon will be listed here.

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.

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