© 1992 Oxford University Press
RESEARCH-ARTICLE |
Cloning and mapping of the 
-adducin gene close to D4S95 and assessment of its relationship to Huntington disease
Department of Medical Genetics, University of British Columbia 416-2125 East Mall, NCE Building, Vancouver, British Columbia V6T 1Z4 1Department of Genetics, Hospital for Sick Children Toronto, Ontario, Canada
* To whom correspondence should be addressed
Received November 11, 1992; Accepted November 13, 1992
The genetic defect underlying Huntington's disease (HD) has been mapped to 4p16.3. Refined localization using recombinant HD chromosome analysis and allelic association analyses have Identified two distinct candidate regions. Using a cDNA hybrid selection procedure we have cloned the gene for 
-adducin, a subunit of a cytoskeletal protein crucial for spectrin-actin membrane plasticity. This gene maps to the proximal 2.2 Mb candidate region within 20 kb of D4S95. Alleles of markers at this locus have been shown to exhibit significant linkage disequilibrium with HD. A 4 kb -adducin transcript was identified which is abundantly expressed in the caudate nucleus, the site of major neuronal loss in HD. Sequencing of the brain -adducin cDNA from two HD patients and an age-matched control did not detect any sequence alterations specific to HD. However, we identified in brain cDNA of both patients and control samples, two alternately spliced brain exons, not previously described in the erythrocyte cDNA. A 93 bp exon is inserted in frame between codon 471 and 472 while a 34 bp exon inserted within codon 621 disrupts the frame and introduces a stop codon after 11 novel amino acids. The mapping of the adducin gene adjacent to D4S95 and its pattern of expression, as well as its potential for distinct alternately spliced variants, reinforces the necessity to accurately assess the role of the expression of this gene in the pathogenesis of HD.