Identification of Novel Genomic Variations in Susceptibility to Nonsyndromic Cleft Lip and Palate Patients

• Published in: Pediatric reports Vol. 13; no. 4; pp. 650 - 657
• Main Authors: Avasthi, Kapil Kumar, Muthuswamy, Srinivasan, Asim, Ambreen, Agarwal, Amit, Agarwal, Sarita
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.12.2021; MDPI
• Subjects: Cleft lip/palate; CLP; Deoxyribonucleic acid; Disease prevention; DNA; Environmental factors; Gene loci; Genetic diversity; genome-wide association; Genomes; Genomics; Health risk assessment; Network analysis; nonsyndromic cleft lip and/or palate; NSCL/P; Nucleotides; Patients; Pediatrics; Peripheral blood; PMRA; Precision medicine; Quality control; Regulatory sequences; Risk management; Single-nucleotide polymorphism; SNPs; Teratogens; Asia; United States > US; India; nonsyndromic cleft lip and/or palate; SNPs; PMRA; genome-wide association; NSCL/P; CLP
• ISSN: 2036-749X; 2036-7503; 2036-7503
• DOI: 10.3390/pediatric13040077

Nonsyndromic cleft lip with or without palate (NSCL/P) is a multifactorial and common birth malformation caused by genetic and environmental factors, as well as by teratogens. Genome-wide association studies found genetic variations with modulatory effects of NSCL/P formation in Chinese and Iranian populations. We aimed to identify the susceptibility of single-nucleotide polymorphisms (SNPs) to nonsyndromic cleft lip with or without palate in the Indian population. The present study was conducted on NSCL/P cases and controls. Genomic DNA was extracted from peripheral blood and Axiom- Precision Medicine Research Array (PMRA) was performed. The Axiom-PMRA covers 902,527 markers and several thousand novel risk variants. Quality control-passed samples were included for candidate genetic variation identification, gene functional enrichment, and pathway and network analysis. The genome-wide association study identified fourteen novel candidate gene SNPs that showed the most significant association with the risk of NSCL/P, and eight were predicted to have regulatory sequences. The GWAS study showed novel candidate genetic variations in NSCL/P formations. These findings contribute to the understanding of genetic predisposition to nonsyndromic cleft lip with or without palate.