講演情報
[OE5-1]長鎖シークエンス技術を用いた転写産物全長のeQTL解析
○名倉 佑哉, 嶋多 美穂子, 藤本 明洋 (東京大学大学院 医学系研究科 国際保健学専攻 人類遺伝学教室)
Expression quantitative trait loci (eQTL) are genetic variants that are related to variations in gene expression levels. Integration of eQTL and results of genome-wide association studies (GWAS) can identify causal genetic variation of diseases, and many eQTL studies have been conducted. However, most previous eQTL studies used short-read sequencers to examine gene expression levels and did not analyze full-length transcripts. Recently long-read sequencing technologies have become available for RNA-seq, which can generate reads longer than 10 kbp and capture splicing variants (SpVs) accurately. In this study, we conducted Nanopore long-read RNA-seq using B cells of 67 Japanese analyzed in the 1000 Genomes Project. eQTLs at SpV-level and gene-level (sum of SpV in each gene) were identified using the result of RNA-seq and genetic variations (SNP and short indel) in autosomes. We detected the expression of 43,691 SpVs from 15,392 genes, in which 6,834 SpVs were novel. From eQTL analysis at SpV-level, we identified 33,955 eQTLs. Of these, 23,434 were SpV-specific and not detected as gene-level eQTLs. Among SpV-specific eQTLs, 379 overlapped with SNPs in the GWAS catalog database. SpV-specific eQTLs were associated with minor SpVs in each gene (p＜＜0.01). We also found that SpV-specific eQTLs were significantly enriched in H3K36me3 regions compared to all eQTLs (gene-level and SpV-level) (OR=1.46, p=2.7×10-31). This study revealed that a lot of variants can affect the expression level of SpV and that analysis of full-length transcripts identifies a large number of novel eQTLs.