Abstract
The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) (z = 5.51 at a recombination fraction theta = 0.11) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed (z = 5.27 at theta = 0.00). Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. Our results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis.
Full text
PDF![7576](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8021/299342/ff89d9bcb5ce/pnas00336-0226.png)
![7577](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8021/299342/19107e624f67/pnas00336-0227.png)
![7578](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8021/299342/23e1f9b3e22d/pnas00336-0228.png)
![7579](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8021/299342/13fba60c00d9/pnas00336-0229.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
- Alwine J. C., Kemp D. J., Parker B. A., Reiser J., Renart J., Stark G. R., Wahl G. M. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. Methods Enzymol. 1979;68:220–242. doi: 10.1016/0076-6879(79)68017-5. [DOI] [PubMed] [Google Scholar]
- Arveiler B., Hofker M. H., Bergen A. A., Mandel J. L. A PstI RFLP detected by probe cpX73 (DXS159) in Xq11-q12. Nucleic Acids Res. 1987 Jul 24;15(14):5903–5903. doi: 10.1093/nar/15.14.5903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drayna D., Davies K., Hartley D., Mandel J. L., Camerino G., Williamson R., White R. Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1984 May;81(9):2836–2839. doi: 10.1073/pnas.81.9.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drayna D., White R. The genetic linkage map of the human X chromosome. Science. 1985 Nov 15;230(4727):753–758. doi: 10.1126/science.4059909. [DOI] [PubMed] [Google Scholar]
- Durandy A., Dumez Y., Guy-Grand D., Oury C., Henrion R., Griscelli C. Prenatal diagnosis of severe combined immunodeficiency. J Pediatr. 1982 Dec;101(6):995–997. doi: 10.1016/s0022-3476(82)80029-2. [DOI] [PubMed] [Google Scholar]
- Geldwerth D., Bishop C., Guellaën G., Koenig M., Vergnaud G., Mandel J. L., Weissenbach J. Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome. EMBO J. 1985 Jul;4(7):1739–1743. doi: 10.1002/j.1460-2075.1985.tb03844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodfellow P. N., Davies K. E., Ropers H. H. Report of the Committee on the Genetic Constitution of the X and Y Chromosomes. Cytogenet Cell Genet. 1985;40(1-4):296–352. doi: 10.1159/000132178. [DOI] [PubMed] [Google Scholar]
- Griscelli C., Durandy A., Virelizier J. L., Ballet J. J., Daguillard F. Selective defect of precursor T cells associated with apparently normal B lymphocytes in severe combined immunodeficiency disease. J Pediatr. 1978 Sep;93(3):404–411. doi: 10.1016/s0022-3476(78)81146-9. [DOI] [PubMed] [Google Scholar]
- Koenig M., Moisan J. P., Heilig R., Mandel J. L. Homologies between X and Y chromosomes detected by DNA probes: localisation and evolution. Nucleic Acids Res. 1985 Aug 12;13(15):5485–5501. doi: 10.1093/nar/13.15.5485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwan S. P., Kunkel L., Bruns G., Wedgwood R. J., Latt S., Rosen F. S. Mapping of the X-linked agammaglobulinemia locus by use of restriction fragment-length polymorphism. J Clin Invest. 1986 Feb;77(2):649–652. doi: 10.1172/JCI112351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mensink E. J., Thompson A., Schot J. D., van de Greef W. M., Sandkuyl L. A., Schuurman R. K. Mapping of a gene for X-linked agammaglobulinemia and evidence for genetic heterogeneity. Hum Genet. 1986 Aug;73(4):327–332. doi: 10.1007/BF00279095. [DOI] [PubMed] [Google Scholar]
- Oberlé I., Camerino G., Kloepfer C., Moisan J. P., Grzeschik K. H., Hellkuhl B., Hors-Cayla M. C., Van Cong N., Weil D., Mandel J. L. Characterization of a set of X-linked sequences and of a panel of somatic cell hybrids useful for the regional mapping of the human X chromosome. Hum Genet. 1986 Jan;72(1):43–49. doi: 10.1007/BF00278816. [DOI] [PubMed] [Google Scholar]
- Page D. C., Harper M. E., Love J., Botstein D. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature. 1984 Sep 13;311(5982):119–123. doi: 10.1038/311119a0. [DOI] [PubMed] [Google Scholar]
- Page D., de Martinville B., Barker D., Wyman A., White R., Francke U., Botstein D. Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5352–5356. doi: 10.1073/pnas.79.17.5352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willard H. F., Skolnick M. H., Pearson P. L., Mandel J. L. Report of the Committee on Human Gene Mapping by Recombinant DNA Techniques. Cytogenet Cell Genet. 1985;40(1-4):360–489. doi: 10.1159/000132180. [DOI] [PubMed] [Google Scholar]