口颌面裂 (OFC) are common congenital birth defects with various
etiologies, including genetic variants. Online Mendelian Inheritance in Man
(我的天啊) annotated several hundred genes involving OFCs. 此外, several
hundreds of de novo variants (DNVs) have been identified from individuals
with OFCs. Some DNVs are related to known OFC genes or pathways, but there
are still many DNVs whose relevance to OFC development is unknown. To
explore novel gene functions and their cellular expression profiles, we
focused on DNVs in genes that were not listed in OMIM. We collected 960
DNVs in 853 genes from published studies and curated these genes, based on
the DNVs’ deleteriousness, into 230 和 23 genes related to cleft lip with
or without cleft palate (CL/P) and cleft palate only (CPO), 分别.
For comparison, we curated 178 CL/P and 277 CPO genes from OMIM. In CL/P,
the pathways enriched in DNV and OMIM genes were significantly overlapped
(p = 0.002). Single-cell RNA sequencing (scRNA-seq) analysis of mouse lip
development revealed that both gene sets had abundant expression in the
ectoderm (DNV genes: adjusted p = 0.032, OMIM genes: adjusted p < 0.0002),
while only DNV genes were enriched in the endothelium (adjusted p = 0.032).
Although we did not achieve significant findings using CPO gene sets, which
was mainly due to the limited number of DNV genes, scRNA-seq analysis
implicated various expression patterns among DNV and OMIM genes. Our
results suggest that combinatory pathway and scRNA-seq data analyses are
helpful for contextualizing genes in OFC development.