Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1998 Jul;63(1):109–119. doi: 10.1086/301907

Evidence that a locus for familial high myopia maps to chromosome 18p.

T L Young 1, S M Ronan 1, L A Drahozal 1, S C Wildenberg 1, A B Alvear 1, W S Oetting 1, L D Atwood 1, D J Wilkin 1, R A King 1
PMCID: PMC1377231  PMID: 9634508

Abstract

Myopia, or nearsightedness, is the most common human eye disorder. A genomewide screen was conducted to map the gene(s) associated with high, early-onset, autosomal dominant myopia. Eight families that each included two or more individuals with >=-6.00 diopters (D) myopia, in two or more successive generations, were identified. Myopic individuals had no clinical evidence of connective-tissue abnormalities, and the average age at diagnosis of myopia was 6.8 years. The average spherical component refractive error for the affected individuals was -9.48 D. The families contained 82 individuals; of these, DNA was available for 71 (37 affected). Markers flanking or intragenic to the genes for Stickler syndrome types 1 and 2 (chromosomes 12q13.1-q13.3 and 6p21.3, respectively), Marfan syndrome (chromosome 15q21.1), and juvenile glaucoma (chromosome 1q21-q31) were also analyzed. No evidence of linkage was found for markers for the Stickler syndrome types 1 and 2, the Marfan syndrome, or the juvenile glaucoma loci. After a genomewide search, evidence of significant linkage was found on chromosome 18p. The maximum LOD score was 9.59, with marker D18S481, at a recombination fraction of .0010. Haplotype analysis further refined this myopia locus to a 7.6-cM interval between markers D18S59 and D18S1138 on 18p11.31.

Full Text

The Full Text of this article is available as a PDF (830.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashton G. C. Segregation analysis of ocular refraction and myopia. Hum Hered. 1985;35(4):232–239. doi: 10.1159/000153551. [DOI] [PubMed] [Google Scholar]
  2. Berg E. S., Olaisen B. Characterization of the COL2A1 VNTR polymorphism. Genomics. 1993 May;16(2):350–354. doi: 10.1006/geno.1993.1196. [DOI] [PubMed] [Google Scholar]
  3. Brunner H. G., van Beersum S. E., Warman M. L., Olsen B. R., Ropers H. H., Mariman E. C. A Stickler syndrome gene is linked to chromosome 6 near the COL11A2 gene. Hum Mol Genet. 1994 Sep;3(9):1561–1564. doi: 10.1093/hmg/3.9.1561. [DOI] [PubMed] [Google Scholar]
  4. Cleary E. G., Gibson M. A. Elastin-associated microfibrils and microfibrillar proteins. Int Rev Connect Tissue Res. 1983;10:97–209. doi: 10.1016/b978-0-12-363710-9.50009-5. [DOI] [PubMed] [Google Scholar]
  5. Cottingham R. W., Jr, Idury R. M., Schäffer A. A. Faster sequential genetic linkage computations. Am J Hum Genet. 1993 Jul;53(1):252–263. [PMC free article] [PubMed] [Google Scholar]
  6. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  7. Dietz H. C., Cutting G. R., Pyeritz R. E., Maslen C. L., Sakai L. Y., Corson G. M., Puffenberger E. G., Hamosh A., Nanthakumar E. J., Curristin S. M. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. doi: 10.1038/352337a0. [DOI] [PubMed] [Google Scholar]
  8. Dubovsky J., Sheffield V. C., Duyk G. M., Weber J. L. Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome. Hum Mol Genet. 1995 Mar;4(3):449–452. doi: 10.1093/hmg/4.3.449. [DOI] [PubMed] [Google Scholar]
  9. Edwards M., Lewis W. H. Autosomal recessive inheritance of myopia in Hong Kong Chinese infants. Ophthalmic Physiol Opt. 1991 Jul;11(3):227–231. [PubMed] [Google Scholar]
  10. Francomano C. A., Liberfarb R. M., Hirose T., Maumenee I. H., Streeten E. A., Meyers D. A., Pyeritz R. E. The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. Genomics. 1987 Dec;1(4):293–296. doi: 10.1016/0888-7543(87)90027-9. [DOI] [PubMed] [Google Scholar]
  11. Goldschmidt E. The importance of heredity and environment in the etiology of low myopia. Acta Ophthalmol (Copenh) 1981 Oct;59(5):759–762. doi: 10.1111/j.1755-3768.1981.tb08743.x. [DOI] [PubMed] [Google Scholar]
  12. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  13. Hoyt C. S., Stone R. D., Fromer C., Billson F. A. Monocular axial myopia associated with neonatal eyelid closure in human infants. Am J Ophthalmol. 1981 Feb;91(2):197–200. doi: 10.1016/0002-9394(81)90173-2. [DOI] [PubMed] [Google Scholar]
  14. Johnson A. T., Drack A. V., Kwitek A. E., Cannon R. L., Stone E. M., Alward W. L. Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. Ophthalmology. 1993 Apr;100(4):524–529. doi: 10.1016/s0161-6420(13)31615-7. [DOI] [PubMed] [Google Scholar]
  15. Karlsson J. L. Evidence of recessive inheritance of myopia. Clin Genet. 1975 Mar;7(3):197–202. doi: 10.1111/j.1399-0004.1975.tb00319.x. [DOI] [PubMed] [Google Scholar]
  16. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  18. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lathrop G. M., Lalouel J. M., White R. L. Construction of human linkage maps: likelihood calculations for multilocus linkage analysis. Genet Epidemiol. 1986;3(1):39–52. doi: 10.1002/gepi.1370030105. [DOI] [PubMed] [Google Scholar]
  20. Lee B., Godfrey M., Vitale E., Hori H., Mattei M. G., Sarfarazi M., Tsipouras P., Ramirez F., Hollister D. W. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991 Jul 25;352(6333):330–334. doi: 10.1038/352330a0. [DOI] [PubMed] [Google Scholar]
  21. Lin L. L., Chen C. J., Hung P. T., Ko L. S. Nation-wide survey of myopia among schoolchildren in Taiwan, 1986. Acta Ophthalmol Suppl. 1988;185:29–33. doi: 10.1111/j.1755-3768.1988.tb02657.x. [DOI] [PubMed] [Google Scholar]
  22. Macklin M. T. HEREDITARY ABNORMALITIES OF THE EYE: VII. INHERITABLE DEFECTS INVOLVING EYE MUSCLES, REFRACTION, ETC. Can Med Assoc J. 1927 Dec;17(12):1493–1498. [PMC free article] [PubMed] [Google Scholar]
  23. Marshall G. E. Human scleral elastic system: an immunoelectron microscopic study. Br J Ophthalmol. 1995 Jan;79(1):57–64. doi: 10.1136/bjo.79.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marshall G. E., Konstas A. G., Bechrakis N. E., Lee W. R. An immunoelectron microscope study of the aged human lens capsule. Exp Eye Res. 1992 Mar;54(3):393–401. doi: 10.1016/0014-4835(92)90051-s. [DOI] [PubMed] [Google Scholar]
  25. Marshall G. E., Konstas A. G., Lee W. R. Immunogold localization of type IV collagen and laminin in the aging human outflow system. Exp Eye Res. 1990 Dec;51(6):691–699. doi: 10.1016/0014-4835(90)90054-x. [DOI] [PubMed] [Google Scholar]
  26. Miller-Meeks M. J., Bennett S. R., Keech R. V., Blodi C. F. Myopia induced by vitreous hemorrhage. Am J Ophthalmol. 1990 Feb 15;109(2):199–203. doi: 10.1016/s0002-9394(14)75987-2. [DOI] [PubMed] [Google Scholar]
  27. Morrison J., Farrell S., Johnson E., Deppmeier L., Moore C. G., Grossmann E. Structure and composition of the rodent lamina cribrosa. Exp Eye Res. 1995 Feb;60(2):127–135. doi: 10.1016/s0014-4835(95)80002-6. [DOI] [PubMed] [Google Scholar]
  28. Oetting W. S., Lee H. K., Flanders D. J., Wiesner G. L., Sellers T. A., King R. A. Linkage analysis with multiplexed short tandem repeat polymorphisms using infrared fluorescence and M13 tailed primers. Genomics. 1995 Dec 10;30(3):450–458. doi: 10.1006/geno.1995.1264. [DOI] [PubMed] [Google Scholar]
  29. Ott J. Linkage analysis and family classification under heterogeneity. Ann Hum Genet. 1983 Oct;47(Pt 4):311–320. doi: 10.1111/j.1469-1809.1983.tb01001.x. [DOI] [PubMed] [Google Scholar]
  30. Rasmussen O. D. INCIDENCE OF MYOPIA IN CHINA: Data and theses from periodical investigations covering thirty years residence, and association with refracting and hospital centres, in a score of the larger cities. Br J Ophthalmol. 1936 Jun;20(6):350–360. doi: 10.1136/bjo.20.6.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ross R., Bornstein P. Elastic fibers in the body. Sci Am. 1971 Jun;224(6):44–52. doi: 10.1038/scientificamerican0671-44. [DOI] [PubMed] [Google Scholar]
  32. Schäffer A. A., Gupta S. K., Shriram K., Cottingham R. W., Jr Avoiding recomputation in linkage analysis. Hum Hered. 1994 Jul-Aug;44(4):225–237. doi: 10.1159/000154222. [DOI] [PubMed] [Google Scholar]
  33. Sheffield V. C., Stone E. M., Alward W. L., Drack A. V., Johnson A. T., Streb L. M., Nichols B. E. Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31. Nat Genet. 1993 May;4(1):47–50. doi: 10.1038/ng0593-47. [DOI] [PubMed] [Google Scholar]
  34. Stone E. M., Fingert J. H., Alward W. L., Nguyen T. D., Polansky J. R., Sunden S. L., Nishimura D., Clark A. F., Nystuen A., Nichols B. E. Identification of a gene that causes primary open angle glaucoma. Science. 1997 Jan 31;275(5300):668–670. doi: 10.1126/science.275.5300.668. [DOI] [PubMed] [Google Scholar]
  35. Teikari J. M., O'Donnell J., Kaprio J., Koskenvuo M. Impact of heredity in myopia. Hum Hered. 1991;41(3):151–156. doi: 10.1159/000153994. [DOI] [PubMed] [Google Scholar]
  36. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  37. Wiggs J. L., Haines J. L., Paglinauan C., Fine A., Sporn C., Lou D. Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees. Genomics. 1994 May 15;21(2):299–303. doi: 10.1006/geno.1994.1269. [DOI] [PubMed] [Google Scholar]
  38. Wilkin D. J., Koprivnikar K. E., Cohn D. H. Heteroduplex analysis can increase the informativeness of PCR-amplified VNTR markers: application using a marker tightly linked to the COL2A1 gene. Genomics. 1993 Feb;15(2):372–375. doi: 10.1006/geno.1993.1070. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES