Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 Jun;64(6):1679–1685. doi: 10.1086/302423

Homozygosity mapping of the Achromatopsia locus in the Pingelapese.

J D Winick 1, M L Blundell 1, B L Galke 1, A A Salam 1, S M Leal 1, M Karayiorgou 1
PMCID: PMC1377911  PMID: 10330355

Abstract

Achromatopsia, or total color blindness (also referred to as "rod monochromacy"), is a severe retinal disorder characterized clinically by an inability to distinguish colors, impaired visual acuity in daylight, photophobia, and nystagmus. Inherited as an autosomal recessive trait, achromatopsia is rare in the general population (1:20,000-1:50,000). Among the Pingelapese people of the Eastern Caroline Islands, however, the disorder occurs at an extremely high frequency, as recounted in Oliver Sacks's popular book The Island of the Colorblind: 4%-10% of this island population have the disorder and approximately 30% carry the gene. This extraordinary enrichment of the disease allele most likely resulted from a sharp reduction in population in the late 18th century, in the aftermath of a typhoon and subsequent geographic and cultural isolation. To obtain insights into the genetic basis of achromatopsia, as well as into the genetic history of this region of Micronesia, a genomewide search for linkage was performed in three Pingelapese kindreds with achromatopsia. A two-step search was used with a DNA pooling strategy, followed by genotyping of individual family members. Genetic markers that displayed a shift toward homozygosity in the affected DNA pool were used to genotype individual members of the kindreds, and an achromatopsia locus was identified on 8q21-q22. A maximal multipoint LOD score of 9.5 was observed with marker D8S1707. Homozygosity was seen for three adjacent markers (D8S275, D8S1119, and D8S1707), whereas recombination was observed with the flanking markers D8S1757 and D8S270, defining the outer boundaries of the disease-gene locus that spans a distance of <6.5cM.

Full Text

The Full Text of this article is available as a PDF (285.7 KB).

Selected References

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

  1. Arbour N. C., Zlotogora J., Knowlton R. G., Merin S., Rosenmann A., Kanis A. B., Rokhlina T., Stone E. M., Sheffield V. C. Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling. Hum Mol Genet. 1997 May;6(5):689–694. doi: 10.1093/hmg/6.5.689. [DOI] [PubMed] [Google Scholar]
  2. Brennan T. M., Landau D., Shalev H., Lamb F., Schutte B. C., Walder R. Y., Mark A. L., Carmi R., Sheffield V. C. Linkage of infantile Bartter syndrome with sensorineural deafness to chromosome 1p. Am J Hum Genet. 1998 Feb;62(2):355–361. doi: 10.1086/301708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brody J. A., Hussels I., Brink E., Torres J. Hereditary blindness among Pingelapese people of Eastern Caroline Islands. Lancet. 1970 Jun 13;1(7659):1253–1257. doi: 10.1016/s0140-6736(70)91740-x. [DOI] [PubMed] [Google Scholar]
  4. Broman K. W., Murray J. C., Sheffield V. C., White R. L., Weber J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998 Sep;63(3):861–869. doi: 10.1086/302011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carr R. E., Morton N. E., Siegel I. M. Achromatopsia in Pingelap Islanders. Study of a genetic isolate. Am J Ophthalmol. 1971 Oct;72(4):746–756. doi: 10.1016/0002-9394(71)90013-4. [DOI] [PubMed] [Google Scholar]
  6. Grimberg J., Nawoschik S., Belluscio L., McKee R., Turck A., Eisenberg A. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res. 1989 Oct 25;17(20):8390–8390. doi: 10.1093/nar/17.20.8390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hussels I. E., Morton N. E. Pingelap and Mokil Atolls: achromatopsia. Am J Hum Genet. 1972 May;24(3):304–309. [PMC free article] [PubMed] [Google Scholar]
  8. Kohl S., Marx T., Giddings I., Jägle H., Jacobson S. G., Apfelstedt-Sylla E., Zrenner E., Sharpe L. T., Wissinger B. Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet. 1998 Jul;19(3):257–259. doi: 10.1038/935. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Lewis R. A., Holcomb J. D., Bromley W. C., Wilson M. C., Roderick T. H., Hejtmancik J. F. Mapping X-linked ophthalmic diseases. III. Provisional assignment of the locus for blue cone monochromacy to Xq28. Arch Ophthalmol. 1987 Aug;105(8):1055–1059. doi: 10.1001/archopht.1987.01060080057028. [DOI] [PubMed] [Google Scholar]
  11. Nathans J., Davenport C. M., Maumenee I. H., Lewis R. A., Hejtmancik J. F., Litt M., Lovrien E., Weleber R., Bachynski B., Zwas F. Molecular genetics of human blue cone monochromacy. Science. 1989 Aug 25;245(4920):831–838. doi: 10.1126/science.2788922. [DOI] [PubMed] [Google Scholar]
  12. Nystuen A., Benke P. J., Merren J., Stone E. M., Sheffield V. C. A cerebellar ataxia locus identified by DNA pooling to search for linkage disequilibrium in an isolated population from the Cayman Islands. Hum Mol Genet. 1996 Apr;5(4):525–531. doi: 10.1093/hmg/5.4.525. [DOI] [PubMed] [Google Scholar]
  13. Parvari R., Hershkovitz E., Kanis A., Gorodischer R., Shalitin S., Sheffield V. C., Carmi R. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43. Am J Hum Genet. 1998 Jul;63(1):163–169. doi: 10.1086/301915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sheffield V. C., Carmi R., Kwitek-Black A., Rokhlina T., Nishimura D., Duyk G. M., Elbedour K., Sunden S. L., Stone E. M. Identification of a Bardet-Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. Hum Mol Genet. 1994 Aug;3(8):1331–1335. doi: 10.1093/hmg/3.8.1331. [DOI] [PubMed] [Google Scholar]
  15. Sheffield V. C., Nishimura D. Y., Stone E. M. Novel approaches to linkage mapping. Curr Opin Genet Dev. 1995 Jun;5(3):335–341. doi: 10.1016/0959-437x(95)80048-4. [DOI] [PubMed] [Google Scholar]
  16. Stockton D. W., Lewis R. A., Abboud E. B., Al-Rajhi A., Jabak M., Anderson K. L., Lupski J. R. A novel locus for Leber congenital amaurosis on chromosome 14q24. Hum Genet. 1998 Sep;103(3):328–333. doi: 10.1007/s004390050825. [DOI] [PubMed] [Google Scholar]
  17. Wang C. Y., Hawkins-Lee B., Ochoa B., Walker R. D., She J. X. Homozygosity and linkage-disequilibrium mapping of the urofacial (Ochoa) syndrome gene to a 1-cM interval on chromosome 10q23-q24. Am J Hum Genet. 1997 Jun;60(6):1461–1467. doi: 10.1086/515469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weeks D. E., Sobel E., O'Connell J. R., Lange K. Computer programs for multilocus haplotyping of general pedigrees. Am J Hum Genet. 1995 Jun;56(6):1506–1507. [PMC free article] [PubMed] [Google Scholar]
  19. Wissinger B., Jägle H., Kohl S., Broghammer M., Baumann B., Hanna D. B., Hedels C., Apfelstedt-Sylla E., Randazzo G., Jacobson S. G. Human rod monochromacy: linkage analysis and mapping of a cone photoreceptor expressed candidate gene on chromosome 2q11. Genomics. 1998 Aug 1;51(3):325–331. doi: 10.1006/geno.1998.5390. [DOI] [PubMed] [Google Scholar]
  20. Wissinger B., Sharpe L. T. New aspects of an old theme: the genetic basis of human color vision. Am J Hum Genet. 1998 Nov;63(5):1257–1262. doi: 10.1086/302127. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES