PURPOSE: We reported previously a 7-base intronic deletion close to the intron/exon junction of the SOD1 gene in 2 separate families with an autosomal-dominant form of keratoconus. The goal of this study was to determine if the 2 families (families A and H) shared a common haplotype by identifying closely linked new microsatellite markers flanking the SOD1 gene. METHODS: Total genomic DNA was extracted from the blood of available members of families A and H. The DNA was amplified by polymerase chain reaction and digested with HpyCH4 III. A genomic contig was first constructed flanking the human SOD1 gene on chromosome 21q22.1-21q22.11. New polymorphic microsatellite markers were identified. All available individuals from the 2 families were genotyped using a set of 7 different markers (SOD1NU10, SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU13, SOD1NU8, and SOD1NU9) to identify phase and the disease haplotype was constructed. RESULTS: Five of the 7 markers are novel (SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU8, and SOD1NU9). Family A is a 3-generation family and the disease haplotype was inferred based on segregation data for 7 different markers. Family H shared only 3 of the disease-associated alleles (SOD1NU1, SOD1NU2, and SOD1NU13) compared with family A. CONCLUSION: Based on the dissimilarity of disease-associated alleles, the 2 families do not appear to share the same haplotype and therefore are not closely related. This strongly supports the uniqueness of the 7-base deletion in intron 2 of the SOD1 gene to the keratoconus phenotype.
PURPOSE: We reported previously a 7-base intronic deletion close to the intron/exon junction of the SOD1 gene in 2 separate families with an autosomal-dominant form of keratoconus. The goal of this study was to determine if the 2 families (families A and H) shared a common haplotype by identifying closely linked new microsatellite markers flanking the SOD1 gene. METHODS: Total genomic DNA was extracted from the blood of available members of families A and H. The DNA was amplified by polymerase chain reaction and digested with HpyCH4 III. A genomic contig was first constructed flanking the humanSOD1 gene on chromosome 21q22.1-21q22.11. New polymorphic microsatellite markers were identified. All available individuals from the 2 families were genotyped using a set of 7 different markers (SOD1NU10, SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU13, SOD1NU8, and SOD1NU9) to identify phase and the disease haplotype was constructed. RESULTS: Five of the 7 markers are novel (SOD1NU1, SOD1NU2, SOD1NU3, SOD1NU8, and SOD1NU9). Family A is a 3-generation family and the disease haplotype was inferred based on segregation data for 7 different markers. Family H shared only 3 of the disease-associated alleles (SOD1NU1, SOD1NU2, and SOD1NU13) compared with family A. CONCLUSION: Based on the dissimilarity of disease-associated alleles, the 2 families do not appear to share the same haplotype and therefore are not closely related. This strongly supports the uniqueness of the 7-base deletion in intron 2 of the SOD1 gene to the keratoconus phenotype.
Authors: Justyna A Karolak; Karolina Kulinska; Dorota M Nowak; Jose A Pitarque; Andrea Molinari; Malgorzata Rydzanicz; Bassem A Bejjani; Marzena Gajecka Journal: Mol Vis Date: 2011-03-30 Impact factor: 2.367
Authors: Shari R Atilano; Daniel H Lee; Paula S Fukuhara; Marilyn Chwa; Anthony B Nesburn; Nitin Udar; M Cristina Kenney Journal: J Ophthalmic Vis Res Date: 2019 Jan-Mar
Authors: Mahsaw N Motlagh; Majid Moshirfar; Michael S Murri; David F Skanchy; Hamed Momeni-Moghaddam; Yasmyne C Ronquillo; Phillip C Hoopes Journal: Med Hypothesis Discov Innov Ophthalmol Date: 2019