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A. Shiels, D.S. Mackay, J.M. King, J.A. Plunkett, H.L. S. Knopf, T.M. Bennett; Locus Refinement for Autosomal Dominant Cataracts on Chromosome 1p . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3284.
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© ARVO (1962-2015); The Authors (2016-present)
To map the gene underlying autosomal dominant "posterior–polar" cataracts segregating in a four–generation Caucasian–American family.
Following ethical approval and informed consent, leukocyte genomic DNA was prepared using protease–digestion, chaotropic–lysis and anion–exchange–spin–columns. Genotyping was preformed using M13–tailed infrared dye–labeled microsatellite markers and automated gel–electrophoresis. Pedigree and haplotype data were managed using the Cyrilic program, and Lod scores were calculated using the Linkage package of programs. Mutation profiling was performed using fluorescent dye–terminator cycle–sequencing and automated capillary electrophoresis.
After exclusion of linkage to loci for posterior–polar cataracts on chromosomes 10q, 11q, 16q and 20cen, we obtained significant evidence of linkage at markers D1S1608 (Lod score [Z] = 3.47, recombination fraction [θ] = 0), D1S2893 (Z = 3.34, θ = 0), and D1S2660 (Z = 3.30, θ = 0) on 1p. Haplotyping indicated that the cataract locus lay in the physical interval D1S243–(4.7Mb)–D1S214. Re–sequencing of six positional–candidate genes failed to detect coding mutations that co–segregated with cataracts in the family.
Our linkage data refine the locus for posterior–polar cataracts on 1p first identified in a British family. The refined cataract interval probably lies centromeric to the Volkmann–type congenital cataract locus identified in a Danish family, and telomeric to the locus for "complete" congenital cataract identified in a Tasmanian family; however, it overlaps the telomeric end of a chromosomal region linked with age–related cortical cataracts.
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