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.
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Change history
05 March 2024
A Correction to this paper has been published: https://doi.org/10.1038/s10038-024-01239-4
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Acknowledgements
The authors would like to thank everyone who contributed to this research. This project was supported by the National Natural Science Foundation of China (No. 82170919) and the Research and Develop Program, West China Hospital of Stomatology Sichuan University (No. RD-03-202301). The authors declare no potential conflicts of interest with respect to the authorship and/ or publication of this article.
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The original online version of this article was revised: In this article Jialin Sun and Mujia Li should have been denoted as equally contributing authors.
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Sun, J., Li, M., Sun, H. et al. Genetic association and functional validation of ZFP36L2 in non-syndromic orofacial cleft subtypes. J Hum Genet 69, 139–144 (2024). https://doi.org/10.1038/s10038-024-01222-z
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DOI: https://doi.org/10.1038/s10038-024-01222-z