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Publication Type
Journal Article
Author, Analytic
Zhu, X.; McKenzie, Colin A.; Forrester, Terrence E.; Nickerson, D. A.; Broeckel, U.; Schunkert, H.; Doering, A.; Jacob, H. J.; Cooper, Richard S.; Rieder, M. J.
Author Affiliation, Ana.
Tropical Medicine Research Institute
Article Title
Localization of a small genomic region associated with elevated ACE
Medium Designator
n/a
Connective Phrase
n/a
Journal Title
American Journal of Human Genetics
Translated Title
n/a
Reprint Status
Refereed
Date of Publication
2000
Volume ID
67
Issue ID
5
Page(s)
1144-53
Language
eng
Connective Phrase
n/a
Location/URL
n/a
ISSN
0002-9297
Notes
n/a
Abstract
Defining the relationship between multiple polymorphisms in a small genomic region and an underlying quantitative trait locus (QTL) represents a major challenge in human genetics. Pedigree analyses have shown that angiotensin I-converting enzyme (ACE) levels are influenced by a QTL located within or close to the ACE gene and most likely resides in the 3' region of this locus. We genotyped seven polymorphisms spanning 13 kb in the 3' end of ACE in 159 Afro-Caribbean subjects to evaluate the linkage disequilibrium between these sites and to narrow the genomic region associated with an elevated ACE level using a cladistic analysis. The linkage disequilibrium measurement D' and a haplotype tree revealed three distinct haplotype segments, presumably because of recombination. The value of the linkage disequilibrium parameter p(excess) was highest for site 22982, which is located in the middle segment. A series of nested, cladistic analyses confirmed that the other two regions are unlikely to be the ACE-linked QTL and that the variant resides in the middle region. Analyses of the same polymorphisms in 98 unrelated Europeans in the Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study resulted in fewer haplotypes than were observed among the Afro-Caribbean subjects, suggesting that populations with greater genetic diversity may be especially informative for fine-scale mapping.....
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