Fibroblast growth factor receptor 2 (FGFR2): genomic sequence and variations

• Published in: Cytogenetic and genome research Vol. 94; no. 3-4; pp. 121 - 126
• Main Authors: Ingersoll, R.G., Paznekas, W.A., Tran, A.K., Scott, A.F., Jiang, G., Jabs, E.W.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2001; S. Karger AG
• Subjects: Alleles; Alternative Splicing - genetics; Base Sequence; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; Cosmids - genetics; craniosynostosis; Diseases of the osteoarticular system; DNA Mutational Analysis; Exons - genetics; FGFR2 gene; Fundamental and applied biological sciences. Psychology; Gene Mapping, Cloning and Sequencing; Genetic Variation - genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome; Human; Humans; Introns - genetics; Medical sciences; Microsatellite Repeats - genetics; Miscellaneous. Osteoarticular involvement in other diseases; Mutagenesis, Insertional - genetics; Polymorphism, Single Nucleotide - genetics; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor - genetics; RNA Splice Sites - genetics; Human; Fibroblast growth factor; Nervous system diseases; Genetic marker; Nucleotide sequence; Craniosynostosis; Diseases of the osteoarticular system; Insertion; Dysostosis; Gene organization; Microsatellite DNA; Skull disease; Mutation; Single nucleotide polymorphism; Polymorphism; Biological receptor
• ISSN: 1424-8581; 0301-0171; 1424-859X
• DOI: 10.1159/000048802

Fibroblast growth factor receptors (FGFRs) play an important role in development and tumorigenesis. Mutations in FGFR2 cause more than five craniosynostosis syndromes. The FGFR2 genomic structure is the largest of the FGFR family. We have refined and extended the genomic organization of the FGFR2 gene by sequencing more than 119 kb of PACs, cosmids, and PCR products and assembling a region of approximately 175 kb. Although the gene structure has been reported to include only 20 exons, we have verified the presence of at least 22 exons, some of which are alternatively spliced. The sizes of six exons differed from those reported previously. Comparison of our sequence and those in the NCBI database detected more than 300 potential single nucleotide polymorphisms (SNPs). However, sequencing regions containing 52 of these potential SNPs verified only 14 in PCR products generated from 16 CEPH alleles. In contrast, direct sequencing of the CEPH DNAs revealed 21 other polymorphisms. Only one SNP was found in the 2,926 bp of coding sequence. Twenty-seven SNPs, two insertion polymorphisms and five microsatellite polymorphisms are contained in approximately 16.6 kb of non-coding sequence. These data yield an average of one polymorphism for approximately 488 bp of non-coding sequence examined. This collection of SNP, insertion, and repeat polymorphisms will aid future association studies between the FGFR2 gene and human disease and will enhance mutation detection.