Abstract
Multiple host genes determine susceptibility or resistance to tuberculosis. In an exome-wide association study conducted among tuberculosis patients and their exposed but clinically asymptomatic household contacts, we found that the SNP rs61104666 located in the fifth exon of SIGLEC15 gene is associated with the disease. No other variant in SIGLEC15 has been reported previously to be associated with tuberculosis. The associated polymorphism results in a synonymous change (E292E) and therefore is unlikely to be involved in disease pathogenesis. Bioinformatic analysis of epigenetic marks in the genomic region reveals an enhancer mark present in lung and blood, downstream to the SIGLEC15 gene may harbor candidate causal SNPs which are in strong LD with the index SNP. This region overlaps with the 3′UTR region of the neighboring gene EPG5. EPG5 has role in autophagy, a phenomenon relevant to clearing of the infection. The region also harbors DNAse I sensitive sites with SNPs of low RegulomeDB score indicative of potential transcription binding sites. All these evidences suggest further exploration of the enhancer region to understand its role in disease manifestation.
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19 July 2019
Due to an oversight an error with respect to SNP number and associated polymorphism was crept in the abstract of the original version. The corrected version of the same should read as follows.
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Acknowledgements
We are grateful to all the study participants. Mr Bijan Bhusan Bairagya is thanked for excellent technical assistance. We are thankful to Dr. Arindam Maitra and CoTeRi for conducting the genotyping and sequencing experiments.
Funding
This work was supported by the grant BT/01/CEIB/11/VI/05 dated 23/11/2011, from Department of Biotechnology (DBT), Government of India, India. Partha P. Majumder was supported by the J.C.Bose Fellowship of the Government of India, Department of Science and Technology. Chandrika Bhattacharyya was supported by Junior and Senior Research Fellowship from University Grant Commission, India.
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BP and PPM planned the study and designed experiments. CB performed the experiments. Data was analysed by CB, PPM. Bioinformatic data mining and analysis done by BP. PPM provided critical insights. BP wrote the manuscript. All the authors read the manuscript, provided suggestions and approved the final manuscript.
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This article is based on the presentation made during 18th All India Congress of Cytology and Genetics and International Symposium on “Translating Genes and Genomes” held at CSIR-Indian Institute of Chemical Biology, Kolkata in collaboration with Archana Sharma Foundation of Calcutta during January 29–31, 2018.
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Pandit, B., Bhattacharyya, C. & Majumder, P.P. SIGLECs and their contribution to tuberculosis. Nucleus 62, 119–125 (2019). https://doi.org/10.1007/s13237-019-00279-y
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DOI: https://doi.org/10.1007/s13237-019-00279-y