Preliminary evaluation of exome sequencing to identify genetic markers of susceptibility to tuberculosis disease

Duncan, Carla; Mehaffy, Carolina

doi:10.1186/s13104-015-1740-5

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…A pilot study was conducted to evaluate exome sequencing to detect markers for TB susceptibility between active TB and latent TB. They identified 1,611 SNPs different from latent TB using the Sure Select kit while 182 SNPs were identified in TB not in latent TB individuals using TruSight kit ( 235 ). However, this study needs to be done in larger sample size.…”

Section: Current Genotyping Methodsmentioning

confidence: 99%

Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

2018

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Tuberculosis (TB) is still remains the major threat for human health worldwide. Several case-control, candidate-gene, family studies and genome-wide association studies (GWAS) suggested the association of host genetic factors to TB susceptibility or resistance in various ethnic populations. Moreover, these factors modulate the host immune responses to tuberculosis. Studies have reported genetic markers to predict TB development in human leukocyte antigen (HLA) and non-HLA genes like killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 etc. Highly polymorphic HLA loci may influence antigen presentation specificities by modifying peptide binding motifs. The recent meta-analysis studies revealed the association of several HLA alleles in particular class II HLA-DRB1 with TB susceptibility and valuable marker for disease development especially in Asian populations. Case-control studies have found the association of HLA-DR2 in some populations, but not in other populations, this could be due to an ethnic specific association of gene variants. Recently, GWAS conducted in case-control and family based studies in Russia, Chinese Han, Morocco, Uganda and Tanzania revealed the association of genes such as ASAP1, Alkylglycerol monooxygenase (AGMO), Forkhead BoxP1 (FOXP1), C-terminal domain phosphatase 1 (UBLCP1) and intergenic SNP rs932347C/T with TB. Whereas, SNP rs10956514A/G were not associated with TB in western Chinese Han and Tibetan population. In this review, we summarize the recent findings of genetic variants with susceptibility/resistance to TB.

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Section: Current Genotyping Methodsmentioning

confidence: 99%

Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

2018

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“…Whole-genome sequencing technologies have enabled the mining of potential genes associated with susceptibility to TB. Using the Sure Select kit, 1611 single nucleotide polymorphisms (SNPs) were identified in ATB but not TBI, while the TruSight kit identified 182 single-nucleotide polymorphisms (SNPs) [ 193 ]. SNPs related to ATB but not with TBI were found to belong to Toll-like receptor-1 (TLR1), vitamin D receptor (VDR), and tumor necrosis factor (TNF) [ 193 ].…”

Section: Evaluation Of Host-derived Biomarkersmentioning

confidence: 99%

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

et al. 2023

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Globally, it is estimated that one-quarter of the world’s population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5–10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.

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“…While results are rarely concordant between populations, GWAS have identified significantly associated variants and meta-analysis of toll-like receptor (TLR) candidate gene associations have identified significantly associated variants across multiple populations (27)(28)(29). The feasibility of using next generation sequencing technologies was demonstrated by an exome sequencing study of five participants (three with a history of active TB and two with a positive TB skin test indicative of latent M.tb infection) (30). This small-scale pilot study presented several potential candidate genes for further investigation.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Genetic Susceptibility to Tuberculous Meningitis

Bowker¹

2022

Front. Neurol.

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Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB) that arises when a caseating meningeal granuloma discharges its contents into the subarachnoid space. It accounts for ~1% of all disease caused by Mycobacterium tuberculosis and the age of peak incidence is from 2–4 years. The exact pathogenesis of TBM is still not fully understood and the mechanism(s) by which the bacilli initially invade the blood-brain-barrier are still to be elucidated. This study investigated the involvement of the host genome in TBM susceptibility, by considering common variants (minor allele frequency (MAF) >5%) using microarray genotyping and rare variants (MAF <1%) via exome sequencing. A total of 123 TBM cases, 400 pulmonary TB (pTB) cases and 477 healthy controls were genotyped on the MEGA array. A genome-wide association study (GWAS) comparing 114 TBM cases to 395 healthy controls showed no association with TBM susceptibility. A second analysis comparing 114 TBM cases to 382 pTB cases was conducted to investigate variants associated with different TB phenotypes. No significant associations were found with progression from pTB to TBM. Ten TBM cases and 10 healthy controls were exome sequenced. Gene set association tests SKAT-O and SKAT Common Rare were used to assess the association of rare SNPs and the cumulative effect of both common and rare SNPs with susceptibility to TBM, respectively. Ingenuity Pathway Analysis (IPA) of the top-hits of the SKAT-O analysis showed that NOD2 and CYP4F2 are both important in TBM pathogenesis and highlighted these as targets for future study. For the SKAT Common Rare analysis Centriolar Coiled-Coil Protein 110 (CCP110) was nominally associated (p = 5.89x10−6) with TBM susceptibility. In addition, several top-hit genes ascribed to the development of the central nervous system (CNS) and innate immune system regulation were identified. Exome sequencing and GWAS of our TBM cohort has identified a single previously undescribed association of CCP110 with TBM susceptibility. These results advance our understanding of TBM in terms of both variants and genes that influence susceptibility. In addition, several candidate genes involved in innate immunity have been identified for further genotypic and functional investigation.

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Preliminary evaluation of exome sequencing to identify genetic markers of susceptibility to tuberculosis disease

Cited by 7 publications

References 43 publications

Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

Deciphering Genetic Susceptibility to Tuberculous Meningitis

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