title: SOD1 haplotypes in familial keratoconus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Ophthalmology, The Eye Institute, University of California Irvine, Orange, CA, USA.
authors: Nitin
authors: N
authors: Udar
authors: Shari R
authors: SR
authors: Atilano
authors: Kent
authors: K
authors: Small
authors: Anthony B
authors: AB
authors: Nesburn
authors: M Cristina
authors: MC
authors: Kenney
mesh_terms: D000483:Alleles; D019781:Corneal Topography; D018900:Dinucleotide Repeats; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007438:Introns; D007640:Keratoconus / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D005819:Genetic Markers; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1