Combining genetic and single-cell expression data reveals cell types and novel candidate genes for orofacial clefting.

ABSTRACT: Non-syndromic cleft lip with/without cleft palate (nsCL/P) is one of the most common birth defects and has a multifactorial etiology. To date, over 45 loci harboring common risk variants have been identified. However, the effector genes at these loci, and the cell types that are affected by risk alleles, remain largely unknown. To address this, we combined genetic data from an nsCL/P genome-wide association study (GWAS) with single-cell RNA sequencing data obtained from the heads of unaffected human embryos. Using the recently developed single-cell disease relevance score (scDRS) approach, we identified two major cell types involved in nsCL/P development, namely the epithelium and the HAND2+ pharyngeal arches (PA). Combining scDRS with co-expression networks and differential gene expressio

SUBMITTER: Siewert A 

PROVIDER: S-EPMC11532359 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature