Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene.
BACKGROUND
Cholesterol 7-alpha-hydroxylase (CYP7A1) is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP) at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD) blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans.


RESULTS
The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP). A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations.


CONCLUSIONS
A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism.
Nakamoto
Kaori
K
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA. knakamoto@kumc.edu
Wang
Shuang
S
Jenison
Robert D
RD
Guo
Grace L
GL
Klaassen
Curtis D
CD
Wan
Yu-Jui Yvonne
YJ
Zhong
Xiao-bo
XB
D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D002790:Cholesterol 7-alpha-Hydroxylase