Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans

Ben Krause-Kyora (), Marcel Nutsua, Lisa Boehme, Federica Pierini, Dorthe Dangvard Pedersen, Sabin-Christin Kornell, Dmitriy Drichel, Marion Bonazzi, Lena Möbus, Peter Tarp, Julian Susat, Esther Bosse, Beatrix Willburger, Alexander H. Schmidt, Jürgen Sauter, Andre Franke, Michael Wittig, Amke Caliebe, Michael Nothnagel, Stefan Schreiber, Jesper L. Boldsen, Tobias L. Lenz and Almut Nebel
Additional contact information
Ben Krause-Kyora: Kiel University
Marcel Nutsua: Kiel University
Lisa Boehme: Kiel University
Federica Pierini: Max Planck Institute for Evolutionary Biology
Dorthe Dangvard Pedersen: University of Southern Denmark
Sabin-Christin Kornell: Kiel University
Dmitriy Drichel: University of Cologne
Marion Bonazzi: Kiel University
Lena Möbus: Kiel University
Peter Tarp: University of Southern Denmark
Julian Susat: Kiel University
Esther Bosse: Kiel University
Beatrix Willburger: DKMS
Alexander H. Schmidt: DKMS
Jürgen Sauter: DKMS
Andre Franke: Kiel University
Michael Wittig: Kiel University
Amke Caliebe: Kiel University
Michael Nothnagel: University of Cologne
Stefan Schreiber: Kiel University
Jesper L. Boldsen: University of Southern Denmark
Tobias L. Lenz: Max Planck Institute for Evolutionary Biology
Almut Nebel: Kiel University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), was very common in Europe till the 16th century. Here, we perform an ancient DNA study on medieval skeletons from Denmark that show lesions specific for lepromatous leprosy (LL). First, we test the remains for M. leprae DNA to confirm the infection status of the individuals and to assess the bacterial diversity. We assemble 10 complete M. leprae genomes that all differ from each other. Second, we evaluate whether the human leukocyte antigen allele DRB1*15:01, a strong LL susceptibility factor in modern populations, also predisposed medieval Europeans to the disease. The comparison of genotype data from 69 M. leprae DNA-positive LL cases with those from contemporary and medieval controls reveals a statistically significant association in both instances. In addition, we observe that DRB1*15:01 co-occurs with DQB1*06:02 on a haplotype that is a strong risk factor for inflammatory diseases today.

Date: 2018
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DOI: 10.1038/s41467-018-03857-x

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