33 research outputs found
Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration
Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 Ă 10â11 for rs4733781; P = 1.0 Ă 10â10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosisâinfected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB
Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans
The Southern African Human Genome Programme is a national initiative that aspires to
unlock the unique genetic character of southern African populations for a better understanding
of human genetic diversity. In this pilot study the Southern African Human Genome
Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern
Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique
variants are identified. Despite the shallow time depth since divergence between the two
main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component
analysis and structure analysis reveal significant (p < 10â6) differentiation, and FST analysis
identifies regions with high divergence. The Coloured individuals show evidence of varying
proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the
Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity,
increasing our understanding of the complex and region-specific history of African populations
and highlighting its potential impact on biomedical research and genetic susceptibility to
disease
Applying, Evaluating and Refining Bioinformatics Core Competencies (An Update from the Curriculum Task Force of ISCB's Education Committee)
Functional polymorphism in aldehyde dehydrogenase-2 gene associated with risk of tuberculosis
The role of host genetic factors in respiratory tract infectious diseases:systematic review, meta-analyses and field synopsis
Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29-2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03-5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; ORâ=â0.79 [0.72-0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidenc
Minimum information required for a DMET experiment reporting
Aim: To provide pharmacogenomics reporting guidelines, the information and tools required for reporting to public omic databases. Material & methods: For effective DMET data interpretation, sharing, interoperability, reproducibility and reporting, we propose the Minimum Information required for a DMET Experiment (MIDE) reporting. Results: MIDE provides reporting guidelines and describes the information required for reporting, data storage and data sharing in the form of XML. Conclusion: The MIDE guidelines will benefit the scientific community with pharmacogenomics experiments, including reporting pharmacogenomics data from other technology platforms, with the tools that will ease and automate the generation of such reports using the standardized MIDE XML schema, facilitating the sharing, dissemination, reanalysis of datasets through accessible and transparent pharmacogenomics data reportin