Multipoint Linkage Analysis of Loci in the Proximal Long Arm of the Human X Chromosome: Application to Mapping the Choroideremia Locus

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1987 Apr 1

PMID 2883887

Citations 14

Authors

J G Lesko

R A Lewis

R L Nussbaum

Affiliations

Soon will be listed here.

Abstract

Choroideremia (McK30310), an X-linked retinal dystrophy, causes progressive night blindness, visual field constriction, and eventual central blindness in affected males by the third to fourth decade of life. The biochemical basis of the disease is unknown, and prenatal diagnosis is not available. Subregional localization of the choroideremia locus to Xq13-22 was accomplished initially by linkage to two restriction-fragment-length polymorphisms (RFLPs), DXYS1 (Xq13-q21.1) and DXS3 (Xq21.3-22). We have now extended our linkage analysis to 12 families using nine RFLP markers between Xp11.3 and Xq26. Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22. The families were also used to measure recombination frequencies between RFLP loci to provide parameters for the program LINKMAP. Multipoint analysis with LINKMAP provided overwhelming evidence for placing the choroideremia locus within the region bounded by DXS1 (Xq11-13) and DXS17 (Xq21.3-q22). At a finer level of resolution, multipoint analysis suggested that the choroideremia locus was proximal to DXS3 (384:1 odds) rather than distal to it. Data were insufficient, however, to distinguish between a gene order that puts choroideremia between DXS3 and DXYS1 and one that places choroideremia proximal to both RFLP loci. These results provide linkage mapping of choroideremia and RFLP loci in this region that will be of use for further genetic studies as well as for clinical applications in this and other human diseases.

Citing Articles

Isolation of anonymous DNA sequences from within a submicroscopic X chromosomal deletion in a patient with choroideremia, deafness, and mental retardation.

Nussbaum R, Lesko J, Lewis R, Ledbetter S, Ledbetter D Proc Natl Acad Sci U S A. 1987; 84(18):6521-5.

PMID: 3476958 PMC: 299109. DOI: 10.1073/pnas.84.18.6521.

Regional localization of polymorphic DNA loci on the proximal long arm of the X chromosome using deletions associated with choroideremia.

Schwartz M, Yang H, Niebuhr E, Rosenberg T, Page D Hum Genet. 1988; 78(2):156-60.

PMID: 3422216 DOI: 10.1007/BF00278188.

X-linked hypohidrotic ectodermal dysplasia: localization within the region Xq11-21.1 by linkage analysis and implications for carrier detection and prenatal diagnosis.

Zonana J, Clarke A, Sarfarazi M, Thomas N, Roberts K, Marymee K Am J Hum Genet. 1988; 43(1):75-85.

PMID: 3163892 PMC: 1715295.

Mapping the gene for X-linked cataracts and microcornea with facial, dental, and skeletal features to Xp22: an appraisal of the Nance-Horan syndrome.

Lewis R Trans Am Ophthalmol Soc. 1989; 87:658-728.

PMID: 2576480 PMC: 1298561.

Haplotype and multipoint linkage analysis in Finnish choroideremia families.

Sankila E, Lehner T, Eriksson A, FORSIUS H, Karna J, Page D Hum Genet. 1989; 84(1):66-70.

PMID: 2575071 DOI: 10.1007/BF00210674.

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