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

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Farbrother, Jane Elizabeth ; Kirov, George ; Owen, Michael John ; Pong-Wong, Ricardo ; Haley, Chris S. ; Guggenheim, Jeremy Andrew (2004)

PURPOSE. To determine the extent to which high myopia in a\ud cohort of 51 U.K. families can be attributed to currently identified genetic loci.\ud METHODS. The families comprised 245 subjects with phenotypic\ud information and DNA available, of whom 170 were classified as affected. Subjects were genotyped for microsatellite markers spanning _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 (http://linkage.rockefeller. edu/soft/gh/ provided in the public domain by Rockefeller University, New York, NY), with additional maximization over the parameter _, the proportion of linked families.\ud RESULTS. Evidence of linkage was found for the MYP3 locus on\ud 12q (two-point Zmax _ 2.54, P _ 0.0003 and multipoint\ud hLOD _ 1.08 at _ _ 0.24, P _ 0.023 for marker D12S332;\ud nonparametric linkage [NPL] _ 1.49, P _ 0.07 for marker\ud D12S1607). For the 17q locus there was weak evidence of\ud excess allele sharing and linkage under a recessive model\ud (NPL _ 1.34, P _ 0.09 for marker D17S956; two-point\ud hLOD _ 1.24 at _ _ 0.30 for marker D17S1795; multipoint\ud hLOD _ 1.24 at _ _ 0.17, P _ 0.014 for marker at 77.68 cM,\ud between markers D17S956 and D17S1853). No significant\ud linkage was found to the MYP2 locus on 18p, or to the\ud COL2A1, COL11A1, and FBN1 genes.\ud CONCLUSIONS. These results suggest that the MYP3 locus on 12q\ud could be responsible for high myopia in approximately 25% of\ud the U.K. families showing apparent autosomal dominant transmission,\ud but that the loci on 18p and 17q are less common\ud causes. Thus, additional loci for high myopia are likely to be\ud the cause of the majority of cases of high myopia in the United Kingdom.
  • References (38)
    38 references, page 1 of 4

    1. Goss DA, Hampton MJ, Wickham MG. Selected review on genetic factors in myopia. J Am Optom Assoc. 1988;59:875- 884.

    2. Guggenheim JA, Kirov G, Hodson SA. The heritability of high myopia: a re-analysis of Goldschmidt's data. J Med Genet. 2000; 37:227-231.

    3. Hammond CJ, Snieder H, Gilbert CE, Spector TD. Genes and environment in refractive error: the twin eye study. Invest Ophthalmol Vis Sci. 2001;42:1232-1236.

    4. Lyhne N, Sjølie AK, Kyvik KO, Green A. The importance of genes and environment for ocular refraction and its determiners: a population based study among 20 - 45 year old twins. Br J Ophthalmol. 2001;85:1470 -1476.

    5. Terwilliger JD, Go¨ring HH. Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design. Hum Biol. 2000;72:63-132.

    6. Naiglin L, Gazagne C, Dallongeville F, et al. A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36. J Med Genet. 2002;39:118 -124.

    7. Paluru P, Ronan SM, Heon E, et al. New locus for autosomal dominant high myopia maps to the long arm of chromosome 17. Invest Ophthalmol Vis Sci. 2003;44:1830 -1836.

    8. Young TL, Ronan SM, Drahozal LA, et al. Evidence that a locus for familial high myopia maps to chromosome 18p. Am J Hum Genet. 1998;63:109 -119.

    9. Young TL, Ronan SM, Alvear AB, et al. A second locus for familial high myopia maps to chromosome 12q. Am J Hum Genet. 1998; 63:1419 -1424.

    10. Lam DSC, Tam POS, Fan DSP, et al. Familial high myopia linkage to chromosome 18p. Ophthalmologica. 2003;217:115-118.

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