Faculty Collaboration Database

Localization of a small genomic region associated with elevated ACE. Am J Hum Genet 2000 Nov;67(5):1144-53

Date

09/23/2000

Pubmed ID

11001581

Pubmed Central ID

PMC1288557

DOI

10.1016/S0002-9297(07)62945-0

Scopus ID

2-s2.0-0033764915 (requires institutional sign-in at Scopus site)   109 Citations

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.

Author List

Zhu X, McKenzie CA, Forrester T, Nickerson DA, Broeckel U, Schunkert H, Doering A, Jacob HJ, Cooper RS, Rieder MJ

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Enzyme Induction
Female
Gene Frequency
Genotype
Germany
Haplotypes
Humans
Jamaica
Linkage Disequilibrium
Male
Middle Aged
Peptidyl-Dipeptidase A
Polymorphism, Single Nucleotide
Quantitative Trait, Heritable