Fine mapping of the keratoconus with cataract locus on chromosome15q and candidate gene analysis

[摘要] Purpose: To report the fine mapping of the keratoconus with cataractlocus on chromosome 15q and the mutational analysis of positionalcandidate genes.Methods: Genotyping of two novel microsatellite markers and a singlenucleotide polymorphism (SNP) in the critical region of linkage forkeratoconus with cataract on 15q was performed. Positional candidategenes (MORF4L1, KIAA1055, ETFA, AWP1, REC14,KIAA1199, RCN2, FAH, IDH3A, MTHFS, ADAMTS7,MAN2C1, PTPN9, KIAA1024, ARNT2, BCL2A1, ISL2,C15ORF22 (P24B), DNAJA4, FLJ14594, CIB2 (KIP2),C15ORF5, and PSMA4) prioritized on the basis of ocularexpression and probable function were screened by PCR-based DNAsequencing methods.Results: We report the refinement of the linkage region forkeratoconus with cataract to an interval of approximately 5.5 Mb flankedby the MAN2C1 gene and the D15S211 marker on chromosome 15q.Mutational analysis of positional candidate genes detected many sequencevariations and single nucleotide polymorphisms. None of the sequencevariants were considered pathogenic as they were also found inunaffected family members and normal control DNA samples.Conclusions: Fine mapping of the keratoconus with cataract locus on15q has reduced the linked region to 5.5 Mb, thereby excluding 28candidate genes. A further 23 candidate genes were excluded by directsequencing methods, although a pathogenic genomic rearrangement orexonic deletion would not have been detected.

[学科分类] 生物化学/生物物理