What role do genome variations play in tuberculosis?

September 7, 2017
This photomicrograph reveals Mycobacterium tuberculosis bacteria using acid-fast Ziehl-Neelsen stain; Magnified 1000 X. The acid-fast stains depend on the ability of mycobacteria to retain dye when treated with mineral acid or an acid-alcohol solution such as the Ziehl-Neelsen, or the Kinyoun stains that are carbolfuchsin methods specific for M. tuberculosis. Credit: public domain

Tuberculosis is caused by Mycobacterium tuberculosis. In 2016, this was the most common causative pathogen for death by infectious diseases. Therefore, investigating the biology of infection and disease development is important in the quest to end tuberculosis. In this study, the authors conducted an integrative analysis of human and pathogen genome variations in tuberculosis. The study is published in Springer Nature's Journal of Human Genetics.

Genome-wide association study (GWAS) is an analysis method in genetics which is used to identify disease-related genome variations by comparing the differences in genotype frequencies in a case and control group. There have been several GWAS regarding susceptibility to . However, previous GWAS have not been based on analysis that accounted for pathogen variations. The possible interplay between the host and pathogen genomic variations is difficult to analyze because both the infected human genome and infecting pathogen genome need to be collected from large numbers of patients. In this research the authors did a systematic exploration of host variations for their association with specific lineages of Mycobacterium tuberculosis, which share the same pathogen genome variations.

This is the first GWAS report identifying the host genetic association with tuberculosis after stratification by pathogen variations. Genotype frequency of a (SNP) was increased in a group of patients infected by specific lineage of Mycobacterium tuberculosis compared with the healthy controls. The increased frequency of the SNP was not observed in a group of patients infected by the other lineage, suggesting the pathogen lineage-specific risk of this human genome variant and importance of analyzing the interaction between the host and pathogen genome variants. The identified SNP locates near CD53 gene, encoding a leukocyte surface glycoprotein and known to have functions in immunity and stress response. Increased gene expression of CD53 was observed in active TB patients and supports its biological roles in susceptibility to tuberculosis.

There have been six major lineages reported worldwide (Gagneux S. et al., PNAS 2006). The authors have already reported a strain-dependent association of HLA class II genes in tuberculosis (Toyo-oka L et al., HLA 2017), thus heterogeneity of the pathogen may be responsible for the inconsistency of previous genetic association studies for tuberculosis.

"Nearly one third of the world's population are infected by Mycobacterium tuberculosis, but only 10% of them show symptoms of TB throughout their life." explains lead author Yosuke Omae. "This research lays the foundations for us to identify who will get TB."

Explore further: A genetic variation may increase tuberculosis susceptibility

More information: Omae Y et al. (2017) Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis, Journal of Human Genetics, DOI: 10.1038/jhg.2017.82

Related Stories

A genetic variation may increase tuberculosis susceptibility

July 21, 2017
Researchers have shown that a single nucleotide change in a gene that affects production of hepcidin—a peptide involved in inflammation, immunity, and control of iron levels—is associated with greater susceptibility to ...

Genetic discovery provides clues to how TB may evade the immune system

March 16, 2015
The largest genetic study of tuberculosis (TB) susceptibility to date has led to a potentially important new insight into how the pathogen manages to evade the immune system. Published today in the journal Nature Genetics, ...

Change in conversion definition may improve TB detection

August 4, 2017
(HealthDay)—A change of QuantiFERON-TB interferon (IFN)γ values from 0.7 IU/mL is associated with an increased incidence in the rate of tuberculosis, according to a study published online July 24 in the American Journal ...

Curcumin may help overcome drug-resistant tuberculosis

March 24, 2016
New research indicates that curcumin—a substance in turmeric that is best known as one of the main components of curry powder—may help fight drug-resistant tuberculosis. In Asia, turmeric is used to treat many health ...

Tuberculosis bacterium may undermine immune regulation to drive disease progression

June 1, 2017
Mycobacterium tuberculosis (Mtb)—may disrupt human immune system regulation processes to promote destruction of lung tissue, according to new research published in PLOS Pathogens.

Recommended for you

Scientists first to use genetic engineering technique to investigate Tourette's

September 25, 2017
Scientists at Rutgers University-New Brunswick are the first to use a genetic engineering technique to create brain cells from the blood cells of individuals in a three-generation family with Tourette syndrome to help determine ...

Newly revealed autism-related genes include genes involved in cancer

September 25, 2017
The identification of genes related to autism spectrum disorder (ASD) could help to better understand the disorder and develop new treatments. While scientists have found many genetic differences in different people with ...

Study reveals an ancient Achilles heel in the human genome

September 21, 2017
In a major study published today, researchers at deCODE genetics use whole-genome data from 14,000 people from across the population of Iceland, including 1500 sets of parents and children, to provide the most detailed portrait ...

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.