PUBLICATION
Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes
- Authors
- Sun, J., Li, M., Sun, H., Lin, Z., Shi, B., Jia, Z.
- ID
- ZDB-PUB-240207-1
- Date
- 2024
- Source
- Journal of Human Genetics 69(3-4): 139-144 (Journal)
- Registered Authors
- Sun, Huaqin
- Keywords
- none
- MeSH Terms
-
- Animals
- Cleft Lip*/genetics
- Cleft Palate*/genetics
- Craniofacial Abnormalities*
- Genetic Predisposition to Disease
- Genotype
- Humans
- Morpholinos
- Polymorphism, Single Nucleotide
- Transcription Factors/genetics
- Zebrafish
- PubMed
- 38321215 Full text @ J. Hum. Genet.
Citation
Sun, J., Li, M., Sun, H., Lin, Z., Shi, B., Jia, Z. (2024) Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes. Journal of Human Genetics. 69(3-4):139-144.
Abstract
Background Non-syndromic orofacial cleft (NSOC) is one of the most common craniofacial malformations with complex etiology. This study aimed to explore the role of specific SNPs in ZFP36L2 and its functional relevance in zebrafish models.
Methods We analyzed genetic data of the Chinese Han population from two previous GWAS, comprising of 2512 cases and 2255 controls. Based on the Hardy-Weinberg Equilibrium (HWE) and minor allele frequency (MAF), SNPs in the ZFP36L2 were selected for association analysis. In addition, zebrafish models were used to clarify the in-situ expression pattern of zfp36l2 and the impact of its Morpholino-induced knockdown.
Results Via association analysis, rs7933 in ZFP36L2 was significantly associated with various non-syndromic cleft lip-only subtypes, potentially conferring a protective effect. Zebrafish embryos showed elevated expression of zfp36l2 in the craniofacial region during critical stages of oral cavity formation. Furthermore, Morpholino-induced knockdown of zfp36l2 led to craniofacial abnormalities, including cleft lip, which was partially rescued by the addition of zfp36l2 mRNA.
Conclusion Our findings highlight the significance of ZFP36L2 in the etiology of NSOC, supported by both human genetic association data and functional studies in zebrafish. These results pave the way for further exploration of targeted interventions for craniofacial malformations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping