Research output: Contribution to journal › Article › peer-review
Novel approach to functional SNPs discovery from genome-wide data reveals promising variants for colon cancer risk. / Korbolina, Elena E.; Brusentsov, Ilja I.; Bryzgalov, Leonid O. et al.
In: Human Mutation, Vol. 39, No. 6, 01.06.2018, p. 851-859.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Novel approach to functional SNPs discovery from genome-wide data reveals promising variants for colon cancer risk
AU - Korbolina, Elena E.
AU - Brusentsov, Ilja I.
AU - Bryzgalov, Leonid O.
AU - Leberfarb, Elena Yu
AU - Degtyareva, Arina O.
AU - Merkulova, Tatyana I.
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - In the majority of colorectal cancer (CRC) cases, the genetic basis of predisposition remains unexplained. The goal of the study was to assess the regulatory SNPs (rSNPs) in the human genome and to reveal SRC drivers based on the available chromatin immunoprecipitation sequencing (ChIP-Seq, ChIA-PET) and transcriptional profiling (RNA-Seq) data. We combined positional (locations within genome regulatory elements) and functional (associated with allele-specific binding and expression) criteria followed by an analysis using genome-wide association studies (GWAS) and minor allele frequency (MAF) datasets. DeSeq2 analysis through 70 CRC patients reinforced the regulatory potential. rSNPs (1,476) that were associated with significant (P < 0.01) allele-specific events resulting in thirty that exhibited a link with CRC according to the MAF and 27, with a risk of malignancy in general according to GWAS. Selected rSNPs may modify the expression of genes for tumor suppressors and the regulators of signaling pathways, including noncoding RNAs. However, the rSNPs from the most represented group affect the expression of genes related to splicing. Our findings strongly suggest that the identified variants might contribute to CRC susceptibility, which indicates that aberrant splicing is one of the key mechanisms for unraveling disease etiopathogenesis and provides useful inputs for interpreting how genotypic variation corresponds to phenotypic outcome.
AB - In the majority of colorectal cancer (CRC) cases, the genetic basis of predisposition remains unexplained. The goal of the study was to assess the regulatory SNPs (rSNPs) in the human genome and to reveal SRC drivers based on the available chromatin immunoprecipitation sequencing (ChIP-Seq, ChIA-PET) and transcriptional profiling (RNA-Seq) data. We combined positional (locations within genome regulatory elements) and functional (associated with allele-specific binding and expression) criteria followed by an analysis using genome-wide association studies (GWAS) and minor allele frequency (MAF) datasets. DeSeq2 analysis through 70 CRC patients reinforced the regulatory potential. rSNPs (1,476) that were associated with significant (P < 0.01) allele-specific events resulting in thirty that exhibited a link with CRC according to the MAF and 27, with a risk of malignancy in general according to GWAS. Selected rSNPs may modify the expression of genes for tumor suppressors and the regulators of signaling pathways, including noncoding RNAs. However, the rSNPs from the most represented group affect the expression of genes related to splicing. Our findings strongly suggest that the identified variants might contribute to CRC susceptibility, which indicates that aberrant splicing is one of the key mechanisms for unraveling disease etiopathogenesis and provides useful inputs for interpreting how genotypic variation corresponds to phenotypic outcome.
KW - Allele-specific events
KW - Colorectal cancer
KW - Functional variants
KW - Gene regulation
KW - SNPs
KW - colorectal cancer
KW - gene regulation
KW - allele-specific events
KW - functional variants
KW - SUPPRESSOR
KW - MICRORNAS
KW - IDENTIFICATION
KW - EPIGENETICS
KW - SART3
KW - TUMOR-REJECTION ANTIGEN
KW - GENES
KW - ASSOCIATION
KW - EXPRESSION
KW - RNA-SEQ DATA
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide/genetics
KW - Genome, Human/genetics
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Colonic Neoplasms/genetics
KW - Gene Frequency
KW - HCT116 Cells
KW - Risk Factors
KW - Genotype
KW - Alleles
UR - http://www.scopus.com/inward/record.url?scp=85044849138&partnerID=8YFLogxK
U2 - 10.1002/humu.23425
DO - 10.1002/humu.23425
M3 - Article
C2 - 29573091
AN - SCOPUS:85044849138
VL - 39
SP - 851
EP - 859
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 6
ER -
ID: 12417563