Welcome To Website IAS

Hot news
Achievement

Independence Award

- First Rank - Second Rank - Third Rank

Labour Award

- First Rank - Second Rank -Third Rank

National Award

 - Study on food stuff for animal(2005)

 - Study on rice breeding for export and domestic consumption(2005)

VIFOTEC Award

- Hybrid Maize by Single Cross V2002 (2003)

- Tomato Grafting to Manage Ralstonia Disease(2005)

- Cassava variety KM140(2010)

Centres
Website links
Vietnamese calendar
Library
Visitors summary
 Curently online :  15
 Total visitors :  7451171

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load
Wednesday, 2015/12/02 | 08:03:18

Paul J. McLaren, Cedric Coulonges, István Bartha, Tobias L. Lenz, Aaron J. Deutsch, Arman Bashirova, Susan Buchbinder, Mary N. Carrington, Andrea Cossarizza, Judith Dalmau, Andrea De Luca, James J. Goedert, Deepti Gurdasani, David W. Haas, Joshua T. Herbeck, Eric O. Johnson, Gregory D. Kirk, Olivier Lambotte, Ma Luo, Simon Mallal, Daniëlle van Manen, Javier Martinez-Picado, Laurence Meyer, José M. Miro, James I. Mullins, Niels Obel, Guido Poli, Manjinder S. Sandhu, Hanneke Schuitemaker, Patrick R. Shea, Ioannis Theodorou, Bruce D. Walker, Amy C. Weintrob, Cheryl A. Winkler, Steven M. Wolinsky, Soumya Raychaudhuri, David B. Goldstein, Amalio Telenti, Paul I. W. de Bakker, Jean-François Zagury, and Jacques Fellay

PNAS 2015 112 (47) 14658-14663; GENETICS

Significance

A proportion of the variation in HIV-1 viral load in the infected population is influenced by host genetics. Using a large sample of infected individuals (n = 6,315) with genome-wide genotype data, we sought to map genomic regions that influence HIV viral load and quantify their impact. We identified amino acid positions located in the binding groove of class I HLA proteins (HLA-A and -B) and SNPs in the chemokine (C-C motif) receptor 5 gene region that together explain 14.5% of the observed variation in HIV viral load. Controlling for these signals, we estimated that an additional 5.5% can be explained by common, additive genetic variation. Thus, we demonstrate that common variants of large effect explain the majority of the host genetic component of HIV viral load.

 Abstract

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. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation—mostly in the HLA and CCR5 regions—explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.

 

See: http://www.pnas.org/content/112/47/14658.full

PNAS NOVEMBER 24, 2015; VOL.112, No. 47: 14658–14663

 

Fig. 4. Regional association plot of the chromosome 3 association peak. Association results for Mb 45.5–47 (Hg19) of chromosome 3 in a subset of individuals genotyped for CCR5Δ32 (n = 5,559). P values were calculated by linear regression, including covariates. The blue diamond, red square, and red diamond indicate the association strength of the top SNP (rs4317138, P = 7.7 × 10−22), Hap-P1 (P = 1.8 × 10−19), and CCR5Δ32 (P = 1.6 × 10−16), respectively. The dashed line indicates genome-wide significance (P = 5 × 10−8).

Back      Print      View: 537

[ Other News ]___________________________________________________
  • Genome-wide analysis of autophagy-associated genes in foxtail millet (Setaria italica L.) and characterization of the function of SiATG8a in conferring tolerance to nitrogen starvation in rice.
  • Arabidopsis small nucleolar RNA monitors the efficient pre-rRNA processing during ribosome biogenesis
  • XA21-specific induction of stress-related genes following Xanthomonas infection of detached rice leaves.
  • Reducing the Use of Pesticides with Site-Specific Application: The Chemical Control of Rhizoctonia solani as a Case of Study for the Management of Soil-Borne Diseases
  • OsJRL, a rice jacalin-related mannose-binding lectin gene, enhances Escherichia coli viability under high-salinity stress and improves salinity tolerance of rice.
  • Production of lipopeptide biosurfactants by Bacillus atrophaeus 5-2a and their potential use in microbial enhanced oil recovery.
  • GhABF2, a bZIP transcription factor, confers drought and salinity tolerance in cotton (Gossypium hirsutum L.).
  • Resilience of cassava (Manihot esculenta Crantz) to salinity: implications for food security in low-lying regions.
  • Cellulose synthase complexes act in a concerted fashion to synthesize highly aggregated cellulose in secondary cell walls of plants
  • No adverse effects of transgenic maize on population dynamics of endophytic Bacillus subtilis strain B916-gfp
  • Identification and expression analysis of OsLPR family revealed the potential roles of OsLPR3 and 5 in maintaining phosphate homeostasis in rice
  • Functional analysis of molecular interactions in synthetic auxin response circuits
  • Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers.
  • Inducible Expression of the De-Novo Designed Antimicrobial Peptide SP1-1 in Tomato Confers Resistance to Xanthomonas campestris pv. vesicatoria.
  • Toward combined delignification and saccharification of wheat straw by a laccase-containing designer cellulosome
  • SNP-based discovery of salinity-tolerant QTLs in a bi-parental population of rice (Oryza sativa)
  • Pinpointing genes underlying the quantitative trait loci for root-knot nematode resistance in palaeopolyploid soybean by whole genome resequencing.
  • Transcriptome- Assisted Label-Free Quantitative Proteomics Analysis Reveals Novel Insights into Piper nigrum -Phytophthora capsici Phytopathosystem.
  • Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants
  • Rapid hyperosmotic-induced Ca2+ responses in Arabidopsis thaliana exhibit sensory potentiation and involvement of plastidial KEA transporters

 

Designed & Powered by WEBSO CO.,LTD