Population-wide genomic study to explore the asymmetric pattern of M. lepromatosis cases in the world Subhrajit Barua, B. Tech* and Prabuddha Gupta, PhD Abstract: Background: Tuberculoid and lepromatous leprosy caused by M. leprae is common worldwide but diffused lepromatous leprosy caused by M. lepromatosis is only confined to Mexico and Brazil. Rationale: The reason behind the asymmetric distribution of M. lepromatosis is still a mystery. The probable cause might be geographic and/or genomic, knowing which, would empower us to prevent and treat leprosy better globally. Strategy: NGS data of whole-genome sequencing from 10 individuals belonging to Mexican and Bangladeshi populations were collected from the 1000genomes database. Differential mutation analysis was done using a bioinformatics pipeline to find out SNVs statistically significant in leprosy related genes. Results: Significant SNVs were found in the HLADR gene, which is responsible for antigen presentation.
Methodology: FASTQ NGS reads were collected from 1000 genomes. We selected two groups of ethnicity, namely Mexican (where M. lepromatosis infection is seen) and Bengali (representing global population which is prone to M. leprae infection).
The differential variant calling pipeline was used from the t-bio.info platform (server.tbio.info) to find out differential mutations between the two groups, Mexican (group 1) and Bengali (group 2). Each group had 10 samples each.
Introduction: Leprosy is a chronic dermatologic infection that has plagued human populations for thousands of years. Mycobacterium leprae, the etiological agent for leprosy has puzzled scientists since its identification, by Hansen in 1873. Leprosy is also one of the earliest recognized diseases which has a proven association with the bacterial pathogen, M. leprae. In 2008, a new bacterium, M. lepromatosis was discovered in Mexico which was also reported to cause leprosy. M. lepromatosis was found to be associated with Diffuse Lepromatous Leprosy (DLL) which is usually seen in the Americas.
It would be interesting to see whether these variations are responsible for the differential susceptibility to the two leprosy pathogens, namely M. leprae and M. lepromatosis in the Indian and Mexican population respectively. In the future, we intend to explore the effects of these variations on the pathogen recognition and antigen presentation. It might be possible that such variations would help explain the question addressed in this project.
Conclusion: • DLL, caused by M. lepromatosis is found mainly in Mexico and some parts of Brazil. This pathogen does not seem to infect people living in the Indian subcontinent although India happens to be the country with almost 60% of the total leprosy cases in the world.
Results: The output file contains standard deviation results that correspond to statistically meaningful genomic variation, namely Substitutions and InsertionsDeletions throughout the human genome, i.e. from Chromosome 1 to 22, X, and Y (since all samples taken were male).
Phylogenetic analysis of M. leprae and M. lepromatosis reveals that both the organisms have evolved from a common ancestor about 13.9 million years ago. Still, most of the human infection of M. lepromatosis has been detected only in Western Mexico and the Caribbean islands only. Although India harbors the largest number of confirmed and newly diagnosed leprosy cases to date, there are no confirmed reports for M. lepromatosis infection in India so far. Therefore, it would be interesting to find out whether the genomics of the two populations plays an important role in defining the susceptibility of the individuals to the leprosy pathogens.
On analysing the HLA-DR gene, we found two significant variations, predominant in the Mexican population (group 1). The two identified substitutions were position: 32443746 :– T to C (3.91628) and position: 32443869 :– to G (4.04559).
• This asymmetric distribution of M. lepromatosis cases might be due to the genomic variations in the leprosy associated genes and the genes responsible for immune response in the two populations. • Significant variations in the HLA-DR gene between the two populations reveal the possible genomic factor to this problem and supports our hypothesis. • Analysis of more such genes would provide more clarity about how cross-population genomics plays an important role in changing the susceptibility towards leprosy pathogens.
Acknowledgement: We investigated the HLA-DR gene, which is responsible for presenting peptides derived from both the leprosy pathogens. It has been seen that variations in this gene or different combinations of HLA alleles in different human beings, leads to different levels of susceptibility to the disease.
• Pine Biotech, USA is acknowledged for providing us with server support (https://server.t-bio.info/) which was utilized to perform all the analyses.
• Author details: Subhrajit Barua subhrajit.barua11@gmail.com