Genetic heterogeneity among blue-cone monochromats

Jeremy Nathans, Irene H. Maumenee, Eberhart Zrenner, Bettina Sadowski, Lindsay T. Sharpe, Richard A. Lewis, Egill Hansen, Thomas Rosenberg, Marianne Schwartz, John R. Heckenlively, Elias Traboulsi, Roger Klingaman, N. Torben Bech-Hansen, G. Robert LaRoche, Roberta A. Pagon, William H. Murphey, Richard Weleber

Research output: Contribution to journalArticle

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Abstract

Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5′ red-3′ green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.

Original languageEnglish (US)
Pages (from-to)987-1000
Number of pages14
JournalAmerican Journal of Human Genetics
Volume53
Issue number5
StatePublished - Nov 1993

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Genetic Heterogeneity
Genes
Retinal Pigments
Homologous Recombination
Genotype
Point Mutation
Mutation
Locus Control Region
Gene Conversion
Chromosomes

ASJC Scopus subject areas

  • Genetics

Cite this

Nathans, J., Maumenee, I. H., Zrenner, E., Sadowski, B., Sharpe, L. T., Lewis, R. A., ... Weleber, R. (1993). Genetic heterogeneity among blue-cone monochromats. American Journal of Human Genetics, 53(5), 987-1000.

Genetic heterogeneity among blue-cone monochromats. / Nathans, Jeremy; Maumenee, Irene H.; Zrenner, Eberhart; Sadowski, Bettina; Sharpe, Lindsay T.; Lewis, Richard A.; Hansen, Egill; Rosenberg, Thomas; Schwartz, Marianne; Heckenlively, John R.; Traboulsi, Elias; Klingaman, Roger; Bech-Hansen, N. Torben; LaRoche, G. Robert; Pagon, Roberta A.; Murphey, William H.; Weleber, Richard.

In: American Journal of Human Genetics, Vol. 53, No. 5, 11.1993, p. 987-1000.

Research output: Contribution to journalArticle

Nathans, J, Maumenee, IH, Zrenner, E, Sadowski, B, Sharpe, LT, Lewis, RA, Hansen, E, Rosenberg, T, Schwartz, M, Heckenlively, JR, Traboulsi, E, Klingaman, R, Bech-Hansen, NT, LaRoche, GR, Pagon, RA, Murphey, WH & Weleber, R 1993, 'Genetic heterogeneity among blue-cone monochromats', American Journal of Human Genetics, vol. 53, no. 5, pp. 987-1000.
Nathans J, Maumenee IH, Zrenner E, Sadowski B, Sharpe LT, Lewis RA et al. Genetic heterogeneity among blue-cone monochromats. American Journal of Human Genetics. 1993 Nov;53(5):987-1000.
Nathans, Jeremy ; Maumenee, Irene H. ; Zrenner, Eberhart ; Sadowski, Bettina ; Sharpe, Lindsay T. ; Lewis, Richard A. ; Hansen, Egill ; Rosenberg, Thomas ; Schwartz, Marianne ; Heckenlively, John R. ; Traboulsi, Elias ; Klingaman, Roger ; Bech-Hansen, N. Torben ; LaRoche, G. Robert ; Pagon, Roberta A. ; Murphey, William H. ; Weleber, Richard. / Genetic heterogeneity among blue-cone monochromats. In: American Journal of Human Genetics. 1993 ; Vol. 53, No. 5. pp. 987-1000.
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