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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

GSTM1 copy number distribution and haplotype structure of the GSTM cluster genomic region in a combined Russian sample. SNP haplotypes in the region of the GSTM cluster are shown. The gap in the center of the plot indicates the edges of the GSTM1 deletion. The branch points represent SNPs at which flanking haplotypes diverge because of mutation or recombination. The thickness of the branches corresponds to the frequency of haplotypes. Blue to red color intensity indicates the allele frequency of individual SNPs used to define the haplotypes, where the major allele is bluer, and the minor allele is redder. The color of the “leaves” at the ends of the branches indicates the GSTM1 state of the chromosomes: green, no copies of GSTM1 (deleted gene; CN0); blue, one functional copy of GSTM1 (CN1)
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Fig2: GSTM1 copy number distribution and haplotype structure of the GSTM cluster genomic region in a combined Russian sample. SNP haplotypes in the region of the GSTM cluster are shown. The gap in the center of the plot indicates the edges of the GSTM1 deletion. The branch points represent SNPs at which flanking haplotypes diverge because of mutation or recombination. The thickness of the branches corresponds to the frequency of haplotypes. Blue to red color intensity indicates the allele frequency of individual SNPs used to define the haplotypes, where the major allele is bluer, and the minor allele is redder. The color of the “leaves” at the ends of the branches indicates the GSTM1 state of the chromosomes: green, no copies of GSTM1 (deleted gene; CN0); blue, one functional copy of GSTM1 (CN1)

Mentions: The output of processing phased Russian genotypes generally supported the results of the haploblock-based analysis. The output was expressed as an unequal occurrence of GSTM1 alleles on different haplotypes (Fig. 2). Understanding the paucity of the SNP set tested, we attempted to increase the resolution by imputing additional genotypes. However, the additional genotypes did not markedly influence the pattern of haplotypes inferred, although the total number of SNPs increased to 49. This might be because none of the new SNPs were closer to the GSTM1 deletion than the two aforementioned SNPs, rs673151 and rs929166, which could be the result of earlier and crucial branching. The relevance of earlier branching was supported by the data from the processing of a set of 356 phased SNPs with a MAF ≥ 0.01 in the CEU sample, in which some SNPs were located at some hundreds of base pairs from the deletion (Fig. 3). Furthermore, in the resulting plot, nonrandom occurrence of particular GSTM1 alleles at different haplotypes was more evident (i.e., the lower left part of the plot was occupied exclusively by haplotypes with a GSTM1 allele) (Fig. 3).Fig. 2


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)

GSTM1 copy number distribution and haplotype structure of the GSTM cluster genomic region in a combined Russian sample. SNP haplotypes in the region of the GSTM cluster are shown. The gap in the center of the plot indicates the edges of the GSTM1 deletion. The branch points represent SNPs at which flanking haplotypes diverge because of mutation or recombination. The thickness of the branches corresponds to the frequency of haplotypes. Blue to red color intensity indicates the allele frequency of individual SNPs used to define the haplotypes, where the major allele is bluer, and the minor allele is redder. The color of the “leaves” at the ends of the branches indicates the GSTM1 state of the chromosomes: green, no copies of GSTM1 (deleted gene; CN0); blue, one functional copy of GSTM1 (CN1)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: GSTM1 copy number distribution and haplotype structure of the GSTM cluster genomic region in a combined Russian sample. SNP haplotypes in the region of the GSTM cluster are shown. The gap in the center of the plot indicates the edges of the GSTM1 deletion. The branch points represent SNPs at which flanking haplotypes diverge because of mutation or recombination. The thickness of the branches corresponds to the frequency of haplotypes. Blue to red color intensity indicates the allele frequency of individual SNPs used to define the haplotypes, where the major allele is bluer, and the minor allele is redder. The color of the “leaves” at the ends of the branches indicates the GSTM1 state of the chromosomes: green, no copies of GSTM1 (deleted gene; CN0); blue, one functional copy of GSTM1 (CN1)
Mentions: The output of processing phased Russian genotypes generally supported the results of the haploblock-based analysis. The output was expressed as an unequal occurrence of GSTM1 alleles on different haplotypes (Fig. 2). Understanding the paucity of the SNP set tested, we attempted to increase the resolution by imputing additional genotypes. However, the additional genotypes did not markedly influence the pattern of haplotypes inferred, although the total number of SNPs increased to 49. This might be because none of the new SNPs were closer to the GSTM1 deletion than the two aforementioned SNPs, rs673151 and rs929166, which could be the result of earlier and crucial branching. The relevance of earlier branching was supported by the data from the processing of a set of 356 phased SNPs with a MAF ≥ 0.01 in the CEU sample, in which some SNPs were located at some hundreds of base pairs from the deletion (Fig. 3). Furthermore, in the resulting plot, nonrandom occurrence of particular GSTM1 alleles at different haplotypes was more evident (i.e., the lower left part of the plot was occupied exclusively by haplotypes with a GSTM1 allele) (Fig. 3).Fig. 2

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