Natural Selection on Exonic SNPs Shapes Allelic Expression Imbalance (AEI) Adaptability in Lung Cancer Progression

Frontiers in Genetics
Jinfei HuangXiangyin Kong

Abstract

Tumors are driven by a sequence of genetic and epigenetic alterations. Previous studies have mostly focused on the roles of somatic mutations in tumorigenesis, but how germline variants act is largely unknown. In this study, we hypothesized that allelic expression imbalance (AEI) participated in the process of germline variants on tumorigenesis. We screened single-nucleotide polymorphisms (SNPs) as representative germline variants. By using 127 patients' RNA sequencing data from paired lung cancer and adjacent normal tissues from public databases, we analyzed the effects of the functional consequence of SNPs, function and conservativeness on genes with AEI. We found that natural selection can affect AEI. Functional adaptability of genes with a high frequency of AEI and a correlation of the incidence of AEI with conservativeness were observed in both adjacent tissues and tumor tissues. Moreover, we observed a higher incidence of AEI in genes with non-synonymous SNPs than in those with synonymous SNPs. However, we also found that AEI was affected by allele expression noise, especially in tumor tissues, which led to an increased proportion of AEI, weakened the effect of natural selection and eliminated the influence of the functio...Continue Reading

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Datasets Mentioned

BETA
GSE40419

Methods Mentioned

BETA
RNA-seq
exome sequencing

Software Mentioned

PhastCons
annovar
goterm
DAVID
Samtools
Ensembl
DAVID ( Database for Annotation , Visualization and Integrated...
BP

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