Biology subjects

Jonathan Pritchard

Publications and source records attributed to Jonathan Pritchard.

3 recordsLinked to original sources

bioRxiv2015

Abundant contribution of short tandem repeats to gene expression variation in humans

Expression quantitative trait loci (eQTLs) are a key tool to dissect cellular processes mediating complex diseases. However, little is known about the role of repetitive elements as eQTLs. We report a genome-wide survey of the contribution of Short Tandem Repeats (STRs), one of the most polymorphic and abundant repeat classes, to gene expression in humans. Our survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays. We used variance partitioning to disentangle the contribution of eSTRs from linked SNPs and indels and found that eSTRs contribute 10%-15% of the cis-heritability mediated by all common variants. Functional genomic analyses showed that eSTRs are enriched in conserved regions, co-localize with regulatory elements, and are predicted to modulate histone modifications. Our results show that eSTRs provide a novel set of regulatory variants and highlight the contribution of repeats to the genetic architecture of quantitative human traits.

Genomics↗

bioRxiv2014

WASP: allele-specific software for robust discovery of molecular quantitative trait loci

Allele-specific sequencing reads provide a powerful signal for identifying molecular quantitative trait loci (QTLs), however they are challenging to analyze and prone to technical artefacts. Here we describe WASP, a suite of tools for unbiased allele-specific read mapping and discovery of molecular QTLs. Using simulated reads, RNA-seq reads and ChIP-seq reads, we demonstrate that our approach has a low error rate and is far more powerful than existing QTL mapping approaches.

Genomics↗

bioRxiv2014

Epigenetic Modifications are Associated with Inter-species Gene Expression Variation in Primates

Changes in gene regulation level have long been thought to play an important role in evolution and speciation, especially in primates. Over the past decade, comparative genomic studies have revealed extensive inter-species differences in gene expression levels yet we know much less about the extent to which regulatory mechanisms differ between species. To begin addressing this gap, we performed a comparative epigenetic study in primate lymphoblastoid cell lines (LCLs), to query the contribution of RNA polymerase II (Pol II) and four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) to inter-species variation in gene expression levels. We found that inter-species differences in mark enrichment near transcription start sites are significantly more often associated with inter-species differences in the corresponding gene expression level than expected by chance alone. Interestingly, we also found that first-order interactions among the histone marks and Pol II do not markedly contribute to the degree of association between the marks and inter-species variation in gene expression levels, suggesting that the marginal effects of the five marks dominate this contribution.

Genomics↗