Genetic variations at 10q26 regions near FGFR2 gene and its association with non-syndromic cleft lip with or without cleft palate.


Raju GT(1), L V K S B(2), Gurramkonda VB(3), Hussain SA(4), Paul SFD(5).
Author information:
(1)Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
(2)Department of Zoology, Guru Ghasidas University, Bilaspur, India.
(3)Division of Genetics, Department of Paediatrics, All India Institute of Medical Sciences
(AIIMS), New Delhi, India.
(4)Department of Plastic Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.
(5)Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. Electronic address: [Email]


OBJECTIVES: In our study, we focussed on three SNPs in the non-coding regions near FGFR2 gene, as studies on non-coding variants in the genome are the novel trends to identify the susceptible loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). FGFR2 gene is selected as a candidate gene based on knock out animal models and the role played in syndromic forms of clefting. FGFR2 gene also plays an important role in FGF signaling pathway during craniofacial development. METHODS: In the present study 148 case-parent triads were assessed for three SNPs rs10749408, rs11199874 and rs10788165 near FGFR2 gene by using TaqMan allelic discrimination method. Transmission disequilibrium test (TDT) was used to find the allelic association. Linkage disequilibrium (LD) between the markers was analysed using Haploview program 4.2. Haplotype transmission effects were estimated using FAMHAP package. The possible parent-of-origin effects were assessed by likelihood based approach. RESULTS: TDT analysis of three SNPs failed to show significant transmission disortion from heterozygous parents to the affected child and are not associated with NSCL/P. Linkage disequilibrium analysis showed strong LD between rs11199874 and rs10788165 SNPs. In the haplotype TDT analysis, GG haplotype of rs11199874-rs10788165 showed significant undertransmission to affected child. No significant parent-of-origin effects were observed. CONCLUSION: The present study on noncoding variants near FGFR2 gene is not associated with NSCL/P. As the numbers of triads included in the study are less, further studies are needed including large sample size to find association with NSCL/P.