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

Iseult Jackson, Valeria Mattiangeli, Lara M. Cassidy, Eileen Murphy, Daniel G. Bradley

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
32 Downloads (Pure)

Abstract

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%.

Original languageEnglish
Pages (from-to)248-251
Number of pages4
JournalEuropean Journal of Human Genetics
Volume31
Issue number2
Early online date28 Nov 2022
DOIs
Publication statusPublished - 01 Feb 2023

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