Linkage analysis of the genetic loci for high myopia on 18p, 12q, and 17q in 51 U.K. families

Invest Ophthalmol Vis Sci. 2004 Sep;45(9):2879-85. doi: 10.1167/iovs.03-1156.


Purpose: To determine the extent to which high myopia in a cohort of 51 U.K. families can be attributed to currently identified genetic loci.

Methods: The families comprised 245 subjects with phenotypic information and DNA available, of whom 170 were classified as affected. Subjects were genotyped for microsatellite markers spanning approximately 40cM regions on 18p (MYP2), 12q (MYP3) and 17q, together with markers flanking COL2A1, COL11A1, and FBN1. Two-point linkage analyses were performed using the same disease gene segregation model as was used in the original publications, followed by nonparametric and multipoint analyses using Genehunter ( provided in the public domain by Rockefeller University, New York, NY), with additional maximization over the parameter alpha, the proportion of linked families.

Results: Evidence of linkage was found for the MYP3 locus on 12q (two-point Zmax = 2.54, P = 0.0003 and multipoint hLOD = 1.08 at alpha = 0.24, P = 0.023 for marker D12S332; nonparametric linkage [NPL] = 1.49, P = 0.07 for marker D12S1607). For the 17q locus there was weak evidence of excess allele sharing and linkage under a recessive model (NPL = 1.34, P = 0.09 for marker D17S956; two-point hLOD = 1.24 at alpha = 0.30 for marker D17S1795; multipoint hLOD = 1.24 at alpha = 0.17, P = 0.014 for marker at 77.68 cM, between markers D17S956 and D17S1853). No significant linkage was found to the MYP2 locus on 18p, or to the COL2A1, COL11A1, and FBN1 genes.

Conclusions: These results suggest that the MYP3 locus on 12q could be responsible for high myopia in approximately 25% of the U.K. families showing apparent autosomal dominant transmission, but that the loci on 18p and 17q are less common causes. Thus, additional loci for high myopia are likely to be the cause of the majority of cases of high myopia in the United Kingdom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping*
  • Chromosomes, Human, Pair 12*
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Human, Pair 18*
  • Cohort Studies
  • Connective Tissue Diseases / genetics
  • Genes, Dominant
  • Genetic Linkage*
  • Humans
  • Lod Score
  • Microsatellite Repeats
  • Myopia / genetics*
  • Quantitative Trait Loci
  • United Kingdom