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; Almut Nebel

doi:10.1038/s41467-018-03857-x

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 SchreiberJesper L. Boldsen, Tobias L. Lenz, Almut Nebel

^*Corresponding author for this work

University of Southern Denmark

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	1569
Journal	Nature Communications
Volume	9
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-03857-x
Publication status	Published - 1 May 2018
Externally published	Yes

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Cite this

Krause-Kyora, B., Nutsua, M., Boehme, L., Pierini, F., Pedersen, D. D., Kornell, S. C., Drichel, D., Bonazzi, M., Möbus, L., Tarp, P., Susat, J., Bosse, E., Willburger, B., Schmidt, A. H., Sauter, J., Franke, A., Wittig, M., Caliebe, A., Nothnagel, M., ... Nebel, A. (2018). Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans. Nature Communications, 9, Article 1569. https://doi.org/10.1038/s41467-018-03857-x

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title = "Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans",

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.",

author = "Ben Krause-Kyora and Marcel Nutsua and Lisa Boehme and Federica Pierini and Pedersen, {Dorthe Dangvard} and Kornell, {Sabin Christin} and Dmitriy Drichel and Marion Bonazzi and Lena M{\"o}bus and Peter Tarp and Julian Susat and Esther Bosse and Beatrix Willburger and Schmidt, {Alexander H.} and J{\"u}rgen Sauter and Andre Franke and Michael Wittig and Amke Caliebe and Michael Nothnagel and Stefan Schreiber and Boldsen, {Jesper L.} and Lenz, {Tobias L.} and Almut Nebel",

year = "2018",

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doi = "10.1038/s41467-018-03857-x",

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Krause-Kyora, B, Nutsua, M, Boehme, L, Pierini, F, Pedersen, DD, Kornell, SC, Drichel, D, Bonazzi, M, Möbus, L, Tarp, P, Susat, J, Bosse, E, Willburger, B, Schmidt, AH, Sauter, J, Franke, A, Wittig, M, Caliebe, A, Nothnagel, M, Schreiber, S, Boldsen, JL, Lenz, TL & Nebel, A 2018, 'Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans', Nature Communications, vol. 9, 1569. https://doi.org/10.1038/s41467-018-03857-x

TY - JOUR

T1 - Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans

AU - Krause-Kyora, Ben

AU - Nutsua, Marcel

AU - Boehme, Lisa

AU - Pierini, Federica

AU - Pedersen, Dorthe Dangvard

AU - Kornell, Sabin Christin

AU - Drichel, Dmitriy

AU - Bonazzi, Marion

AU - Möbus, Lena

AU - Tarp, Peter

AU - Susat, Julian

AU - Bosse, Esther

AU - Willburger, Beatrix

AU - Schmidt, Alexander H.

AU - Sauter, Jürgen

AU - Franke, Andre

AU - Wittig, Michael

AU - Caliebe, Amke

AU - Nothnagel, Michael

AU - Schreiber, Stefan

AU - Boldsen, Jesper L.

AU - Lenz, Tobias L.

AU - Nebel, Almut

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-03857-x

DO - 10.1038/s41467-018-03857-x

M3 - Journal article

C2 - 29717136

AN - SCOPUS:85046350691

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 1569

ER -