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Dissertation
Attempts to localise the gene for Friedreich's ataxia: a study done in American familes
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Sep 1995
DOI:
https://doi.org/10.17918/00007305
Abstract
Friedreich's ataxia is an autosomal recessive disease that is manifested by progressive degeneration of the central and peripheral nervous system. Cardiomyopathy is a common finding in Friedreich's patients. The Friedreich's ataxia gene locus (FRDA) has been mapped to the proximal long arm of chromosome 9 (Chamberlain et al.,1988). Five markers assigned to region 9q13-21 form a very tight genetic and physical linkage group with the FRDA locus. The order of the markers in the linkage group is tel-GS4-MCT112 (D9S15)-GS2-26P (D9S5)-FD1-cen (Fujita et al., 1991; Sirugo et al., 1992; Duclos et al., 1993). We have collected blood from 34 families throughout the United States, in order to perform linkage analysis with these markers using standard Restriction Fragment Length Polymorphism and Microsatellite Typing by PCR. Our results demonstrate that these markers are linked to the disease in the American population. During our analysis we detected a recombination event in a family that has the phenotypic criteria for Friedreich's ataxia, except for cardiomyopathy. The recombination occurred such that an affected male inherited a defective maternal chromosome, and only the GS4 and MCT112 markers from the defective paternal chromosome and GS2, 26P and FD1 from the normal paternal chromosome. The recombination suggests that FRDA is excluded from the D9S5 (26P) locus of the linkage group. We now have to identify a distal flanking marker for the critical FRDA region. Two new markers GATA7D12 and UT6023 have been identified 1 and 2-3cM distal to GS4, respectively (Genome Data Base). We typed our families with the marker GATA7D12, and found it to be linked to FRDA in our families. At present linkage analysis is being done with UT6023, with the hope that a recombination event between the disease and marker would help define a distal flanking marker.
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Details
- Title
- Attempts to localise the gene for Friedreich's ataxia
- Creators
- Allison Raechelle D'Costa
- Contributors
- James E. Sylvester (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- ix, 115 unnumbered pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1993-1996, 1998-2002); Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888869504721