Análise genômica comparativa e filogeográfica do Mycobacterium leprae

Article abstract
Nature Genetics 41, 1282 - 1289 (2009)
Published online: 1 November 2009 | doi:10.1038/ng.477

Comparative genomic and phylogeographic analysis of Mycobacterium leprae

Marc Monot1,19, Nadine Honoré1,19, Thierry Garnier1, Nora Zidane1, Diana Sherafi1, Alberto Paniz-Mondolfi2, Masanori Matsuoka3, G Michael Taylor4, Helen D Donoghue4, Abi Bouwman5, Simon Mays6, Claire Watson7, Diana Lockwood7, Ali Khamispour8, Yahya Dowlati8, Shen Jianping9, Thomas H Rea10, Lucio Vera-Cabrera11, Mariane M Stefani12, Sayera Banu13, Murdo Macdonald14, Bishwa Raj Sapkota14, John S Spencer15, Jérôme Thomas16, Keith Harshman16, Pushpendra Singh17, Philippe Busso17, Alexandre Gattiker18, Jacques Rougemont18, Patrick J Brennan15 & Stewart T Cole17

Abstract

Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6 coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38coverage) and NHDP63 (46 coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

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Institut Pasteur, Paris, France.

Instituto de Biomedicina, Caracas, Venezuela.

Leprosy Research Centre, National Institute of Infectious Diseases, Tokyo, Japan.
Centre for Infectious Diseases and International Health, Windeyer Institute, University College London, London, UK.

Faculty of Life Sciences, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK.

Ancient Monuments Laboratory, English Heritage Centre for Archaeology, Fort Cumberland, Portsmouth, UK.

London School of Hygiene and Tropical Medicine, London, UK.

Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.

National Center for Leprosy Control, China Center for Disease Control and Prevention, Nanjing, China.

Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Servicio de Dermatología, Hospital Universitario 'José E. González', Monterrey, Nuevo León, México.

Tropical Pathology and Public Health Institute at Federal University of Goias, Setor Universitario, Goiania, Goias, Brazil.

International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.

Leprosy Mission Nepal, Anandaban Hospital, Kathmandu, Nepal.

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.

DNA Array Facility, Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.

Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Bioinformatics and Biostatistics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

These authors contributed equally to this work.

Correspondence to: Stewart T Cole17 e-mail: stewart.cole@epfl.ch

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