Research Article: The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia

Date Published: , 2012

Publisher: A.I. Gordeyev

Author(s): E.A. Trifonova, E.R. Eremina, F.D. Urnov, V.A. Stepanov.



The structure of the haplotypes and linkage disequilibrium (LD) of the
methylenetetrahydrofolate reductase gene (MTHFR) in 9
population groups from Northern Eurasia and populations of the international
HapMap project was investigated in the present study. The data suggest that the
architecture of LD in the human genome is largely determined by the evolutionary
history of populations; however, the results of phylogenetic and haplotype
analyses seems to suggest that in fact there may be a common “old”
mechanism for the formation of certain patterns of LD. Variability in the
structure of LD and the level of diversity of MTHFRhaplotypes
cause a certain set of tagSNPs with an established prognostic significance for
each population. In our opinion, the results obtained in the present study are
of considerable interest for understanding multiple genetic phenomena: namely,
the association of interpopulation differences in the patterns of LD with
structures possessing a genetic susceptibility to complex diseases, and the
functional significance of the pleiotropicMTHFR gene effect.
Summarizing the results of this study, a conclusion can be made that the genetic
variability analysis with emphasis on the structure of LD in human populations
is a powerful tool that can make a significant contribution to such areas of
biomedical science as human evolutionary biology, functional genomics, genetics
of complex diseases, and pharmacogenomics.

Partial Text

Genetic variability underlies the human phenotypic variation and plays a significant
role in explaining the differences between individuals in their susceptibility to
complex diseases (CD) and in determining the metabolic pathways involved in the
development of pathological processes. Single nucleotide polymorphisms (SNPs)
represent the most common type of genome variability. Thanks to the efforts of the
International SNP Consortium, ~ 10 million SNPs with an approximate density of
1 polymorphism per 300 bp have currently been identified [1]. Each new allele of a polymorphic variant emerges from an
already existing haplotype, the ancestral variant of a particular marker originally
being associated with its alleles. New haplotypes are formed via the accumulation of
new mutations and recombinations. The coinheritance of alleles in a haplotype
manifests itself at the population level as the linkage disequilibrium (LD).


Genetic diversity and haplotype structure at the

This investigation of the architecture of linkage disequilibrium of the MTHFR
locus in nine populations inhabiting northern Eurasia was based on a
conception assuming that the human genome has a block structure. The data relating
to the Caucasian, Chinese, Japanese, and Yoruba populations obtained in the HapMap
project were used as a basis for population comparisons.