Faculty Collaboration Database

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes. BMC Genet 2004 May 24;5:11

Date

05/26/2004

Pubmed ID

15157284

Pubmed Central ID

PMC421754

DOI

10.1186/1471-2156-5-11

Scopus ID

2-s2.0-25444510847 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

BACKGROUND: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers.

RESULTS: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene.

CONCLUSION: The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Author List

Long JR, Zhao LJ, Liu PY, Lu Y, Dvornyk V, Shen H, Liu YJ, Zhang YY, Xiong DH, Xiao P, Deng HW

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

Apolipoproteins E
Carrier Proteins
Collagen Type I
Estrogen Receptor alpha
Family Health
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Ion Channels
Linkage Disequilibrium
Male
Mitochondrial Proteins
Obesity
Osteoporosis
Polymorphism, Single Nucleotide
Receptor, Parathyroid Hormone, Type 1
Receptors, Calcitriol
Receptors, Cell Surface
Receptors, Estrogen
Receptors, Leptin
Statistics as Topic
Transforming Growth Factor beta
Transforming Growth Factor beta1
Uncoupling Protein 3