Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1992 Mar;50(3):590–597.

Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families

Chris F Inglehearn, Douglas H Lester, Rumaisa Bashir, Uzma Atif, T Jeffrey Keen, Amalia Sertedaki, Janet Lindsey, Marcelle Jay, Alan C Bird, G Jane Farrar, Peter Humphries, Shomi S Bhattacharya
PMCID: PMC1684283  PMID: 1539595

Abstract

Autosomal dominant retinitis pigmentosa (adRP) has shown linkage to the chromosome 3q marker C17 (D3S47) in two large adRP pedigrees known as TCDM1 and adRP3. On the basis of this evidence the rhodopsin gene, which also maps to 3q, was screened for mutations which segregated with the disease in adRP patients, and several have now been identified. However, we report that, as yet, no rhodopsin mutation has been found in the families first linked to C17. Since no highly informative marker system is available in the rhodopsin gene, it has not been possible to measure the genetic distance between rhodopsin and D3S47 accurately. We now present a linkage analysis between D3S47 and the rhodopsin locus (RHO) in five proven rhodopsin–retinitis pigmentosa (rhodopsin-RP) families, using the causative mutations as highly informative polymorphic markers. The distance, between RHO and D3S47, obtained by this analysis is θ = .12, with a lod score of 4.5. This contrasts with peak lod scores between D3S47 and adRP of 6.1 at θ = .05 and 16.5 at θ = 0 in families adRP3 and TCDM1, respectively. These data would be consistent with the hypothesis that TCDM1 and ADRP3 represent a second adRP locus on chromosome 3q, closer to D3S47 than is the rhodopsin locus. This result shows that care must be taken when interpreting adRP exclusion data generated with probe C17 and that it is probably not a suitable marker for predictive genetic testing in all chromosome 3q–linked adRP families.

Full text

PDF
594

Selected References

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

  1. Attwood J., Bryant S. A computer program to make linkage analysis with LIPED and LINKAGE easier to perform and less prone to input errors. Ann Hum Genet. 1988 Jul;52(Pt 3):259–259. doi: 10.1111/j.1469-1809.1988.tb01103.x. [DOI] [PubMed] [Google Scholar]
  2. Blanton S. H., Cottingham A. W., Giesenschlag N., Heckenlively J. R., Humphries P., Daiger S. P. Further evidence of exclusion of linkage between type II autosomal dominant retinitis pigmentosa (ADRP) and D3S47 on 3q. Genomics. 1990 Sep;8(1):179–181. doi: 10.1016/0888-7543(90)90243-n. [DOI] [PubMed] [Google Scholar]
  3. Dryja T. P., McGee T. L., Hahn L. B., Cowley G. S., Olsson J. E., Reichel E., Sandberg M. A., Berson E. L. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990 Nov 8;323(19):1302–1307. doi: 10.1056/NEJM199011083231903. [DOI] [PubMed] [Google Scholar]
  4. Dryja T. P., McGee T. L., Reichel E., Hahn L. B., Cowley G. S., Yandell D. W., Sandberg M. A., Berson E. L. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990 Jan 25;343(6256):364–366. doi: 10.1038/343364a0. [DOI] [PubMed] [Google Scholar]
  5. Farrar G. J., McWilliam P., Bradley D. G., Kenna P., Lawler M., Sharp E. M., Humphries M. M., Eiberg H., Conneally P. M., Trofatter J. A. Autosomal dominant retinitis pigmentosa: linkage to rhodopsin and evidence for genetic heterogeneity. Genomics. 1990 Sep;8(1):35–40. doi: 10.1016/0888-7543(90)90223-h. [DOI] [PubMed] [Google Scholar]
  6. Inglehearn C. F., Bashir R., Lester D. H., Jay M., Bird A. C., Bhattacharya S. S. A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa. Am J Hum Genet. 1991 Jan;48(1):26–30. [PMC free article] [PubMed] [Google Scholar]
  7. Inglehearn C. F., Jay M., Lester D. H., Bashir R., Jay B., Bird A. C., Wright A. F., Evans H. J., Papiha S. S., Bhattacharya S. S. No evidence for linkage between late onset autosomal dominant retinitis pigmentosa and chromosome 3 locus D3S47 (C17): evidence for genetic heterogeneity. Genomics. 1990 Jan;6(1):168–173. doi: 10.1016/0888-7543(90)90462-4. [DOI] [PubMed] [Google Scholar]
  8. Jiménez J. B., Samanns C., Watty A., Pongratz J., Olsson J. E., Dickinson P., Buttery R., Gal A., Denton M. J. No evidence of linkage between the locus for autosomal dominant retinitis pigmentosa and D3S47 (C17) in three Australian families. Hum Genet. 1991 Jan;86(3):265–267. doi: 10.1007/BF00202406. [DOI] [PubMed] [Google Scholar]
  9. Kaplan J., Bonneau D., Frézal J., Munnich A., Dufier J. L. Clinical and genetic heterogeneity in retinitis pigmentosa. Hum Genet. 1990 Oct;85(6):635–642. doi: 10.1007/BF00193589. [DOI] [PubMed] [Google Scholar]
  10. Kaplan J., Guasconi G., Dufier J. L., Michel-Awad A., David A., Munnich A., Frezal J. Exclusion of linkage between D3S47 (C17) and ADRPII gene in two large families of moderate autosomal dominant retinitis pigmentosa: evidence for genetic heterogeneity. Ann Genet. 1990;33(3):152–154. [PubMed] [Google Scholar]
  11. Keen J., Lester D., Inglehearn C., Curtis A., Bhattacharya S. Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels. Trends Genet. 1991 Jan;7(1):5–5. doi: 10.1016/0168-9525(91)90004-a. [DOI] [PubMed] [Google Scholar]
  12. Keen T. J., Inglehearn C. F., Lester D. H., Bashir R., Jay M., Bird A. C., Jay B., Bhattacharya S. S. Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site. Genomics. 1991 Sep;11(1):199–205. doi: 10.1016/0888-7543(91)90119-y. [DOI] [PubMed] [Google Scholar]
  13. Lester D. H., Inglehearn C. F., Bashir R., Ackford H., Esakowitz L., Jay M., Bird A. C., Wright A. F., Papiha S. S., Bhattacharya S. S. Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity. Am J Hum Genet. 1990 Sep;47(3):536–541. [PMC free article] [PubMed] [Google Scholar]
  14. Lyness A. L., Ernst W., Quinlan M. P., Clover G. M., Arden G. B., Carter R. M., Bird A. C., Parker J. A. A clinical, psychophysical, and electroretinographic survey of patients with autosomal dominant retinitis pigmentosa. Br J Ophthalmol. 1985 May;69(5):326–339. doi: 10.1136/bjo.69.5.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Massof R. W., Finkelstein D. Rod sensitivity relative to cone sensitivity in retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1979 Mar;18(3):263–272. [PubMed] [Google Scholar]
  16. McWilliam P., Farrar G. J., Kenna P., Bradley D. G., Humphries M. M., Sharp E. M., McConnell D. J., Lawler M., Sheils D., Ryan C. Autosomal dominant retinitis pigmentosa (ADRP): localization of an ADRP gene to the long arm of chromosome 3. Genomics. 1989 Oct;5(3):619–622. doi: 10.1016/0888-7543(89)90031-1. [DOI] [PubMed] [Google Scholar]
  17. Nathans J., Piantanida T. P., Eddy R. L., Shows T. B., Hogness D. S. Molecular genetics of inherited variation in human color vision. Science. 1986 Apr 11;232(4747):203–210. doi: 10.1126/science.3485310. [DOI] [PubMed] [Google Scholar]
  18. Naylor S. L., Bishop D. T. Report of the committee on the genetic constitution of chromosome 3. Cytogenet Cell Genet. 1989;51(1-4):106–120. doi: 10.1159/000132783. [DOI] [PubMed] [Google Scholar]
  19. Naylor S. L., Carritt B. Report of the committee on the genetic constitution of chromosome 3. Cytogenet Cell Genet. 1990;55(1-4):92–96. doi: 10.1159/000132999. [DOI] [PubMed] [Google Scholar]
  20. Olsson J. E., Samanns C., Jimenez J., Pongratz J., Chand A., Watty A., Seuchter S. A., Denton M., Gal A. Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3. Am J Med Genet. 1990 Apr;35(4):595–599. doi: 10.1002/ajmg.1320350434. [DOI] [PubMed] [Google Scholar]
  21. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  22. Sealey P. G., Whittaker P. A., Southern E. M. Removal of repeated sequences from hybridisation probes. Nucleic Acids Res. 1985 Mar 25;13(6):1905–1922. doi: 10.1093/nar/13.6.1905. [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