Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Two common polymorphisms in the APO A‐IV coding gene: Their evolution and linkage disequilibrium

Two common polymorphisms in the APO A‐IV coding gene: Their evolution and linkage disequilibrium Human apolipoprotein A‐IV (APO A‐IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A‐IV coding region has revealed another common nucleotide substitution at codon 347 which converts the commonly present threonine residue (allele A) into serine (allele T). In order to investigate the extent of genetic variation at codon 347, we screened DNA samples from 192 unrelated individuals using a polymerase chain reaction based assay. The frequencies of the two alleles, A‐IV*A and A‐IV*T, were 0.81 and 0.19, respectively, with average heterozygosity 0.31. Genetic screening of the corresponding 192 plasma samples by IEF gave frequencies of 0.922 and 0.078 for the A‐IV*1 and A‐IV*2 alleles, respectively, at codon 360 with average heterozygosity 0.14. Genotype data at the two polymorphic sites were used to assign unequivocal haplotypes to all the 384 chromosomes. Of the expected four haplotypes (A1, T1, A2, and T2) only three were observed and their frequencies were 0.732 for A1, 0.190 for T1 and 0.078 for A2, with average heterozygosity 0.42. Although our data indicate significant linkage disequilibrium between the two sites (χ12 = 7.65, P>0.006, standardized disequilibrium constant ψ = −0.14) the degree of nonrandom association varied between alleles at the two sites. Based upon allele frequency data and variable linkage disequilibrium between alleles, we propose that the A2 and T1 haplotypes may have evolved from the parental A1 haplotype by two independent mutations. © 1992 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genetic Epidemiology Wiley

Two common polymorphisms in the APO A‐IV coding gene: Their evolution and linkage disequilibrium

Loading next page...
 
/lp/wiley/two-common-polymorphisms-in-the-apo-a-iv-coding-gene-their-evolution-rPABQoPj5M

References (39)

Publisher
Wiley
Copyright
Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company
ISSN
0741-0395
eISSN
1098-2272
DOI
10.1002/gepi.1370090503
pmid
1427020
Publisher site
See Article on Publisher Site

Abstract

Human apolipoprotein A‐IV (APO A‐IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A‐IV coding region has revealed another common nucleotide substitution at codon 347 which converts the commonly present threonine residue (allele A) into serine (allele T). In order to investigate the extent of genetic variation at codon 347, we screened DNA samples from 192 unrelated individuals using a polymerase chain reaction based assay. The frequencies of the two alleles, A‐IV*A and A‐IV*T, were 0.81 and 0.19, respectively, with average heterozygosity 0.31. Genetic screening of the corresponding 192 plasma samples by IEF gave frequencies of 0.922 and 0.078 for the A‐IV*1 and A‐IV*2 alleles, respectively, at codon 360 with average heterozygosity 0.14. Genotype data at the two polymorphic sites were used to assign unequivocal haplotypes to all the 384 chromosomes. Of the expected four haplotypes (A1, T1, A2, and T2) only three were observed and their frequencies were 0.732 for A1, 0.190 for T1 and 0.078 for A2, with average heterozygosity 0.42. Although our data indicate significant linkage disequilibrium between the two sites (χ12 = 7.65, P>0.006, standardized disequilibrium constant ψ = −0.14) the degree of nonrandom association varied between alleles at the two sites. Based upon allele frequency data and variable linkage disequilibrium between alleles, we propose that the A2 and T1 haplotypes may have evolved from the parental A1 haplotype by two independent mutations. © 1992 Wiley‐Liss, Inc.

Journal

Genetic EpidemiologyWiley

Published: Jan 1, 1992

Keywords: polymerase chain reaction; genotypes; haplotypes

There are no references for this article.