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GSTM1 copy number variation in the context of single nucleotide polymorphisms in the human GSTM cluster.

Khrunin AV, Filippova IN, Aliev AM, Tupitsina TV, Slominsky PA, Limborska SA - Mol Cytogenet (2016)

Bottom Line: However, taking into account that the deletion has no crucial effects on human well-being, and the ability of other GSTMs to compensate for the lack of GSTM1, a role for additional factors affecting GSTM1 deletion can be proposed.Real-time polymerase chain reaction was used to quantify the number of GSTM1 copies.The observed differences in haplotype patterns suggest the potential role of genetic context in GSTM1 deletion frequency (appearance) and in the determination of the deletion-related effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics of Russian Academy of Sciences, Kurchatov sq. 2, Moscow, 123182 Russia.

ABSTRACT

Background: GSTM1 gene deletion is one of the most known copy number polymorphisms in human genome. It is most likely caused by homologous recombination between the repeats flanking the gene. However, taking into account that the deletion has no crucial effects on human well-being, and the ability of other GSTMs to compensate for the lack of GSTM1, a role for additional factors affecting GSTM1 deletion can be proposed. Our goal was to explore the relationships between GSTM1 deletion polymorphism and single nucleotide polymorphisms (SNPs) in the region of the GSTM cluster that includes GSTM2, GSTM3, GSTM4, and GSTM5 in addition to GSTM1.

Results: Real-time polymerase chain reaction was used to quantify the number of GSTM1 copies. Fourteen SNPs from the region were tested and their allelic patterns were compared in groups of Russian individuals subdivided according to their GSTM1 deletion genotypes. Linkage disequilibrium-based haplotype analysis showed substantial differences of haplotype frequencies between the groups, especially between individuals with homozygous GSTM1 -/- and +/+ genotypes. Exploration of the results of phasing of GSTM1 and SNP genotypes revealed unequal segregation of GSTM1 + and - alleles at different haplotypes.

Conclusions: The observed differences in haplotype patterns suggest the potential role of genetic context in GSTM1 deletion frequency (appearance) and in the determination of the deletion-related effects.

No MeSH data available.


Related in: MedlinePlus

Linkage disequilibrium (LD) between SNPs in the region of the GSTM cluster in a combined Russian sample. A standard Haploview D′/LOD color scheme is used to demonstrate LD, with bright red for strong LD (LOD ≥ 2, D′ = 1), white for no LD (LOD < 2, D′ < 1), shades of pink/red for intermediate LD (LOD ≥ 2, D′ < 1), and blue for statistically ambiguous LD (LOD < 2, D′ = 1) [14]. Numbers in cells represent D′ values between pairs of SNPs (empty cells indicate that D′ = 1 between the corresponding SNPs). Black triangles indicate inferred haplotype blocks
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Fig1: Linkage disequilibrium (LD) between SNPs in the region of the GSTM cluster in a combined Russian sample. A standard Haploview D′/LOD color scheme is used to demonstrate LD, with bright red for strong LD (LOD ≥ 2, D′ = 1), white for no LD (LOD < 2, D′ < 1), shades of pink/red for intermediate LD (LOD ≥ 2, D′ < 1), and blue for statistically ambiguous LD (LOD < 2, D′ = 1) [14]. Numbers in cells represent D′ values between pairs of SNPs (empty cells indicate that D′ = 1 between the corresponding SNPs). Black triangles indicate inferred haplotype blocks

Mentions: Fourteen SNPs determined as located in the region of the GSTM cluster were found among SNPs from the Illumina chip analyses and used in the current study. Figure 1 shows the LD between the SNPs, and the haploblocks inferred in the combined Russian sample. In total, four haploblocks were inferred in the chromosome region. We started our analysis from haplotypes of haploblock 2, comprising SNPs rs673151 and rs929166. These SNPs were the nearest to the region of the GSTM1 deletion. The frequencies of haplotypes CT and TT were maximal in the group of individuals with a GSTM1 +/+ genotype, while the third haplotype, CG, was the most frequent among the carriers of the GSTM1 −/− genotype. All three haplotypes had intermediate frequencies in the group of individuals with the GSTM1 −/+ genotype (Table 2). The same picture of haplotype distribution (i.e., intermediate values of haplotype frequencies in the group of individuals with the GSTM1 −/+ genotype) was observed for haploblocks 1, 3, and 4 (Table 2). As a consequence, pairwise comparisons of haplotypes showed the greatest differences between individuals with the GSTM1 −/− genotype and individuals with the GSTM1 +/+ genotype. Haplotype distributions in all four blocks were significantly different between these two groups (Table 3). A slightly lower number of significant differences were found between the groups with GSTM1 −/− and GSTM −/+ genotypes, and only one when the group with the GSTM1 +/+ genotype was compared with the group with the GSTM −/+ genotype. The same analysis was also carried out in the CEU population. The found correlations in haplotype distributions were similar to those observed in the Russian sample.Fig. 1


GSTM1 copy number variation in the context of single nucleotide polymorphisms in the human GSTM cluster.

Khrunin AV, Filippova IN, Aliev AM, Tupitsina TV, Slominsky PA, Limborska SA - Mol Cytogenet (2016)

Linkage disequilibrium (LD) between SNPs in the region of the GSTM cluster in a combined Russian sample. A standard Haploview D′/LOD color scheme is used to demonstrate LD, with bright red for strong LD (LOD ≥ 2, D′ = 1), white for no LD (LOD < 2, D′ < 1), shades of pink/red for intermediate LD (LOD ≥ 2, D′ < 1), and blue for statistically ambiguous LD (LOD < 2, D′ = 1) [14]. Numbers in cells represent D′ values between pairs of SNPs (empty cells indicate that D′ = 1 between the corresponding SNPs). Black triangles indicate inferred haplotype blocks
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837583&req=5

Fig1: Linkage disequilibrium (LD) between SNPs in the region of the GSTM cluster in a combined Russian sample. A standard Haploview D′/LOD color scheme is used to demonstrate LD, with bright red for strong LD (LOD ≥ 2, D′ = 1), white for no LD (LOD < 2, D′ < 1), shades of pink/red for intermediate LD (LOD ≥ 2, D′ < 1), and blue for statistically ambiguous LD (LOD < 2, D′ = 1) [14]. Numbers in cells represent D′ values between pairs of SNPs (empty cells indicate that D′ = 1 between the corresponding SNPs). Black triangles indicate inferred haplotype blocks
Mentions: Fourteen SNPs determined as located in the region of the GSTM cluster were found among SNPs from the Illumina chip analyses and used in the current study. Figure 1 shows the LD between the SNPs, and the haploblocks inferred in the combined Russian sample. In total, four haploblocks were inferred in the chromosome region. We started our analysis from haplotypes of haploblock 2, comprising SNPs rs673151 and rs929166. These SNPs were the nearest to the region of the GSTM1 deletion. The frequencies of haplotypes CT and TT were maximal in the group of individuals with a GSTM1 +/+ genotype, while the third haplotype, CG, was the most frequent among the carriers of the GSTM1 −/− genotype. All three haplotypes had intermediate frequencies in the group of individuals with the GSTM1 −/+ genotype (Table 2). The same picture of haplotype distribution (i.e., intermediate values of haplotype frequencies in the group of individuals with the GSTM1 −/+ genotype) was observed for haploblocks 1, 3, and 4 (Table 2). As a consequence, pairwise comparisons of haplotypes showed the greatest differences between individuals with the GSTM1 −/− genotype and individuals with the GSTM1 +/+ genotype. Haplotype distributions in all four blocks were significantly different between these two groups (Table 3). A slightly lower number of significant differences were found between the groups with GSTM1 −/− and GSTM −/+ genotypes, and only one when the group with the GSTM1 +/+ genotype was compared with the group with the GSTM −/+ genotype. The same analysis was also carried out in the CEU population. The found correlations in haplotype distributions were similar to those observed in the Russian sample.Fig. 1

Bottom Line: However, taking into account that the deletion has no crucial effects on human well-being, and the ability of other GSTMs to compensate for the lack of GSTM1, a role for additional factors affecting GSTM1 deletion can be proposed.Real-time polymerase chain reaction was used to quantify the number of GSTM1 copies.The observed differences in haplotype patterns suggest the potential role of genetic context in GSTM1 deletion frequency (appearance) and in the determination of the deletion-related effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics of Russian Academy of Sciences, Kurchatov sq. 2, Moscow, 123182 Russia.

ABSTRACT

Background: GSTM1 gene deletion is one of the most known copy number polymorphisms in human genome. It is most likely caused by homologous recombination between the repeats flanking the gene. However, taking into account that the deletion has no crucial effects on human well-being, and the ability of other GSTMs to compensate for the lack of GSTM1, a role for additional factors affecting GSTM1 deletion can be proposed. Our goal was to explore the relationships between GSTM1 deletion polymorphism and single nucleotide polymorphisms (SNPs) in the region of the GSTM cluster that includes GSTM2, GSTM3, GSTM4, and GSTM5 in addition to GSTM1.

Results: Real-time polymerase chain reaction was used to quantify the number of GSTM1 copies. Fourteen SNPs from the region were tested and their allelic patterns were compared in groups of Russian individuals subdivided according to their GSTM1 deletion genotypes. Linkage disequilibrium-based haplotype analysis showed substantial differences of haplotype frequencies between the groups, especially between individuals with homozygous GSTM1 -/- and +/+ genotypes. Exploration of the results of phasing of GSTM1 and SNP genotypes revealed unequal segregation of GSTM1 + and - alleles at different haplotypes.

Conclusions: The observed differences in haplotype patterns suggest the potential role of genetic context in GSTM1 deletion frequency (appearance) and in the determination of the deletion-related effects.

No MeSH data available.


Related in: MedlinePlus