Abstract
The gene responsible for Krabbe disease, an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC), was localized by multipoint linkage analysis on chromosome 14. Eight mapped dinucleotide repeat polymorphisms were tested for linkage to GALC. Two-point linkage analysis demonstrated close linkage of GALC and D14S48, with Z = 13.69 at theta = 0. Multipoint analysis yielded strong support for this finding, with maximum likelihood for GALC located within 1 cM of D14S48. This analysis also identified markers that clearly flank the GALC locus, as the map order of D14S53-GALC-D14S45 is favored by odds greater than 10(6):1. Additional support for close linkage of GALC and D14S48 comes from the apparent linkage disequilibrium between these two loci in a consanguineous Druze community in Israel. These data localize GALC to 14q24.3-q32.1.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Hofker M. H., Smith S., Nakamura Y., Teshima I., White R., Cox D. W. Physical mapping of probes within 14q32, a subtelomeric region showing a high recombination frequency. Genomics. 1990 Jan;6(1):33–38. doi: 10.1016/0888-7543(90)90445-z. [DOI] [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]
- Luty J. A., Litt M. Dinucleotide repeat polymorphism at the D14S45 locus. Nucleic Acids Res. 1991 Aug 11;19(15):4308–4308. doi: 10.1093/nar/19.15.4308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lyerla T. A., Konola J. T., Skiba M. C., Raghavan S. Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17. Am J Hum Genet. 1989 Feb;44(2):198–207. [PMC free article] [PubMed] [Google Scholar]
- Sharma V., Smith L., Allen L., Magenis R. E., Litt M. Dinucleotide repeat polymorphism at the D14S43 locus. Nucleic Acids Res. 1991 Apr 11;19(7):1722–1722. doi: 10.1093/nar/19.7.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang Z., Weber J. L. Continuous linkage map of human chromosome 14 short tandem repeat polymorphisms. Genomics. 1992 Jul;13(3):532–536. doi: 10.1016/0888-7543(92)90121-8. [DOI] [PubMed] [Google Scholar]
- Zlotogora J., Chakraborty S., Knowlton R. G., Wenger D. A. Krabbe disease locus mapped to chromosome 14 by genetic linkage. Am J Hum Genet. 1990 Jul;47(1):37–44. [PMC free article] [PubMed] [Google Scholar]
- Zlotogora J., Regev R., Zeigler M., Iancu T. C., Bach G. Krabbe disease: increased incidence in a highly inbred community. Am J Med Genet. 1985 Aug;21(4):765–770. doi: 10.1002/ajmg.1320210420. [DOI] [PubMed] [Google Scholar]