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A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus

ABSTRACT: A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus

PROVIDER: PRJNA967606 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24443444_1.fastq.gz	Fastqsanger.gz
	SRR24443444_2.fastq.gz	Fastqsanger.gz
	SRR24443445_1.fastq.gz	Fastqsanger.gz
	SRR24443445_2.fastq.gz	Fastqsanger.gz
	SRR24443446_1.fastq.gz	Fastqsanger.gz

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A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus [RNA-Seq]

Project description:A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus [RNA-Seq]

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A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ChIP-Seq]

Project description:A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ChIP-Seq]

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A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ATAC-Seq]

Project description:A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ATAC-Seq]

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A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus [RNA-Seq]

Project description:To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNLPs) may also confer disease risk. Multiple reports have shown that the 5p15.33 prostate cancer (PCa) risk region is a particularly strong expression quantitative trait locus (eQTL) for IRX4 transcripts. Here, we demonstrate using epigenome and genome editing that a biallelic (47bp/21bp) MNLP is the causal variant regulating IRX4 transcript levels. In LNCaP PCa cells (homozygous for the short allele), a single copy knock-in of the long allele potently alters the chromatin state, enabling de novo functional binding of the androgen receptor (AR) associated with increased chromatin accessibility, H3K27 acetylation, and ~3-fold upregulation of IRX4 expression. We further show that an MNLP is amongst the strongest candidate susceptibility variants at two additional PCa risk loci. We estimated that at least 5% of PCa risk loci could be explained by functional non-SNP causal variants, which may have broader implications for other cancers GWAS. More generally, our results underscore the importance of investigating other classes of inherited variation as causal mediators of human traits.

2023-07-11 | GSE231747 | GEO

A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ATAC-Seq]

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A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-11 | GSE231751 | GEO

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