45 Result(s)
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Jonathan K. Pritchard
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Bayesian estimation of gene constraint from an evolutionary model with gene features
Measures of selective constraint on genes have been used for many applications, including clinical interpretation of rare coding variants, disease gene discovery and studies of genome evolution. However, widel...
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Base-editing mutagenesis maps alleles to tune human T cell functions
CRISPR-enabled screening is a powerful tool for the discovery of genes that control T cell function and has nominated candidate targets for immunotherapies1–6. However, new approaches are required to probe specif...
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Systematic differences in discovery of genetic effects on gene expression and complex traits
Most signals in genome-wide association studies (GWAS) of complex traits implicate noncoding genetic variants with putative gene regulatory effects. However, currently identified regulatory variants, notably e...
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CRISPR screens decode cancer cell pathways that trigger γδ T cell detection
γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen background1–5. γδ T cells can sense conserved cell s...
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A genetic history of continuity and mobility in the Iron Age central Mediterranean
The Iron Age was a dynamic period in central Mediterranean history, with the expansion of Greek and Phoenician colonies and the growth of Carthage into the dominant maritime power of the Mediterranean. These e...
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Open AccessNarcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanism...
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Open AccessPrecise modulation of transcription factor levels identifies features underlying dosage sensitivity
Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage ...
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Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks
Gene regulatory networks ensure that important genes are expressed at precise levels. When gene expression is sufficiently perturbed, it can lead to disease. To understand how gene expression disruptions perco...
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RNA editing underlies genetic risk of common inflammatory diseases
A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) map** of genetic variants with...
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A natural mutator allele shapes mutation spectrum variation in mice
Although germline mutation rates and spectra can vary within and between species, common genetic modifiers of the mutation rate have not been identified in nature1. Here we searched for loci that influence germli...
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Author Correction: Genetics of 35 blood and urine biomarkers in the UK Biobank
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Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantit...
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Shared heritability of human face and brain shape
Evidence from model organisms and clinical genetics suggests coordination between the develo** brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivaria...
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Genetics of 35 blood and urine biomarkers in the UK Biobank
Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n = 363,228 individuals). We identify 5,...
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Landscape of stimulation-responsive chromatin across diverse human immune cells
A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully charac...
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Open AccessPost-translational buffering leads to convergent protein expression levels between primates
Differences in gene regulation between human and closely related species influence phenotypes that are distinctly human. While gene regulation is a multi-step process, the majority of research concerning diver...
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Annotation-free quantification of RNA splicing using LeafCutter
The excision of introns from pre-mRNA is an essential step in mRNA processing. We developed LeafCutter to study sample and population variation in intron splicing. LeafCutter identifies variable splicing event...
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Open AccessBatch effects and the effective design of single-cell gene expression studies
Single-cell RNA sequencing (scRNA-seq) can be used to characterize variation in gene expression levels at high resolution. However, the sources of experimental noise in scRNA-seq are not yet well understood. W...
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Tracing the peopling of the world through genomics
Advances in the sequencing and the analysis of the genomes of both modern and ancient peoples have facilitated a number of breakthroughs in our understanding of human evolutionary history. These include the di...
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Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution
Howard Chang, Ravindra Majeti and colleagues define the chromatin accessibility and transcriptional landscapes in 13 human primary blood cell types and in acute myeloid leukemia cells. They identify potential ...
