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Paul Jack Mc Laren

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Related publications (32)

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GuavaH: a compendium of host genomic data in HIV biology and disease

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha

Background: There is an ever-increasing volume of data on host genes that are modulated during HIV infection, influence disease susceptibility or carry genetic variants that impact HIV infection. We created GuavaH (Genomic Utility for Association and Viral ...

BioMed Central2014

HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control

Jacques Fellay, Paul Jack Mc Laren, Nimisha Chaturvedi

Genetic variation in the peptide-binding groove of the highly polymorphic HLA class I molecules has repeatedly been associated with HIV-1 control and progression to AIDS, accounting for up to 12% of the variation in HIV-1 set point viral load (spVL). This ...

National Academy of Sciences2019

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. ...

National Academy of Sciences2015

Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha

Loss-of-function variants in innate immunity genes are associated with Mendelian disorders in the form of primary immunodeficiencies. Recent resequencing projects report that stop-gains and frameshifts are collectively prevalent in humans and could be resp ...

Public Library Science2014

Disentangling human tolerance and resistance against HIV

Jacques Fellay, Paul Jack Mc Laren

In ecology, "disease tolerance" is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from ...

Public Library Science2014

Human genetic variation in HIV disease: beyond genome-wide association studies

Jacques Fellay, Paul Jack Mc Laren

PURPOSE OF REVIEW: Rapid expansion of genomic technologies has resulted in an unprecedented ability to interrogate the impact of human genetic variation on disease. HIV-1 infection is a unique model for studying this impact because host genetic variation i ...

Lippincott Williams & Wilkins2015

European genetic diversity and susceptibility to pathogens

Jacques Fellay, Paul Jack Mc Laren

Infectious diseases, both in their endemic and epidemic forms, have shaped the human genome. Ecology has also contributed to geographically constrained pressures on human populations. There are now multiple examples of population-specific genetic variants ...

2013

Privacy-Preserving Computation of Disease Risk by Using Genomic, Clinical, and Environmental Data

Jean-Pierre Hubaux, Jacques Fellay, Paul Jack Mc Laren, Erman Ayday, Jean Louis Raisaro

According to many scientists and clinicians, genomics is the "next big thing" in the field of medicine. On one hand, decreasing costs in genome sequencing has been paving the way to better preventive and personalized medicine. On the other hand, genomic da ...

2013

Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease

Jacques Fellay, Paul Jack Mc Laren

Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR ...

National Academy of Sciences2013

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses

Paul Jack Mc Laren, Danielle Thompson

Background: Known antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction ...

Biomed Central Ltd2015

A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence ...

Elife Sciences Publications Ltd2013

Exome Sequencing Reveals Primary Immunodeficiencies in Children with Community-Acquired Pseudomonas aeruginosa Sepsis

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha, Samira Asgari

One out of three pediatric sepsis deaths in high income countries occur in previously healthy children. Primary immunodeficiencies (PIDs) have been postulated to underlie fulminant sepsis, but this concept remains to be confirmed in clinical practice. Pseu ...

Frontiers Media Sa2016

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Jacques Fellay, Paul Jack Mc Laren

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated fact ...

Oxford University Press2013

The impact of host genetic variation on infection with HIV-1

Paul Jack Mc Laren

The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibili ...

Nature Publishing Group2015

Estimating the Respective Contributions of Human and Viral Genetic Variation to HIV Control

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha

We evaluated the fraction of variation in HIV-1 set point viral load attributable to viral or human genetic factors by using joint host/pathogen genetic data from 541 HIV infected individuals. We show that viral genetic diversity explains 29% of the variat ...

Public Library of Science2017

A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression

Jacques Fellay, Paul Jack Mc Laren

Objective: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest ris ...

Public Library of Science2014

Defining the role of common variation in the genomic and biological architecture of adult human height

Paul Jack Mc Laren, Jiancheng Yang, Murielle Bochud, Jian Yang

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that th ...

Nature Publishing Group2014

Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls

Jacques Fellay, Paul Jack Mc Laren

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have b ...

Public Library Science2013

Privacy-preserving genomic testing in the clinic: a model using HIV treatment

Jean-Pierre Hubaux, Jacques Fellay, Erman Ayday, Jean Louis Raisaro, Paul Jack Mc Laren, Istvan Bartha

The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical is ...

Nature Publishing Group2016

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

Jacques Fellay, Paul Jack Mc Laren, Istvan Bartha, Christian Hammer

The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,36 ...

Cell Press2015