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Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard



Only a limited number of genetic diseases are diagnosable in archaeological individuals and none have had causal mutations identified in genome-wide screens. Two individuals from the Gaelic Irish Medieval burial ground of Ballyhanna, Co. Donegal, showed evidence of bone tumours consistent with the autosomal dominant condition multiple osteochondromas. Genome sequencing of the earlier individual uncovered a missense mutation in the second exon of EXT1, a specific lesion that has been identified in several modern patients. The later individual lacked this but displayed a novel frameshift mutation leading to a premature stop codon and loss of function in the same gene. These molecular confirmations of a paleopathological diagnosis within a single rural ancient context are surprisingly disjunct, given the observation of clusters of this disease in modern isolated populations and a de novo mutation rate of only 10%.

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Fig. 1: Examples of lesions and alignment of NGS data at putative disease variants.
Fig. 2: Principal component analysis of Northwest European populations.

Data availability

Raw FASTQ and aligned BAM files are available from the European Nucleotide Archive (ENA) under accession number PRJEB50653.


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We acknowledge Trinseq for sequencing support and the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities. We wish to thank the National Museum of Ireland for granting the necessary licences for the study (licence to alter: 6861). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.


We wish to thank Transport Infrastructure Ireland and Donegal County Council who funded the Ballyhanna Research Project. This work was funded by the Science Foundation Ireland/Health Research Board/Wellcome Trust Biomedical Research Partnership Investigator Award No. 205072 to DGB, “Ancient Genomics and the Atlantic Burden” and IJ was supported by the Science Foundation Ireland Centre for Research Training in Genomics Data Science (18/CRT/6214).

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DGB and EM supervised the study. EM curated samples. IJ, VM and LMC generated data through laboratory work. IJ processed and analysed the data with input from LMC. IJ, EM and DGB wrote the paper with input from all authors.

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Correspondence to Eileen Murphy or Daniel G. Bradley.

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This research was carried out under the approval of the Trinity College Dublin School of Natural Sciences Research Ethics Committee, reference number 2019–03.

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Jackson, I., Mattiangeli, V., Cassidy, L.M. et al. Millennium-old pathogenic Mendelian mutation discovery for multiple osteochondromas from a Gaelic Medieval graveyard. Eur J Hum Genet 31, 248–251 (2023).

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