View Full Version : Ballyhanna M222 ancient DNA

02-11-2022, 09:58 AM
Taken from the new DNA papers thread, but it looks like we now have two aDNA M222 sequences from the massive Ballyhanna site in South Donegal:

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 tumors 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%.
Competing Interest Statement

The authors have declared no competing interest.


Radiocarbon dating revealed that the two individuals were definitely not contemporaneous and were potentially separated by several hundred years. Of the two, Sk331 lived more recently (dated AD 1031-1260; UBA-11442) (Figure S1; Table S1) and was the more severe case. He displayed extensive bilateral osteochondromas, both sessile and pedunculated in form, on most bones throughout his skeleton (Figure 1 b.). He also had a short stature compared to other adult males at Ballyhanna (158.3 cm), displayed a major deformity of his left forearm due to shortening of the ulna (Type 15), had unequal bone lengths due to the lesions, as well as a range of orthopaedic deformities that affected his hips, knees and left ankle; all of which are consistent with this condition6. He died as a young adult (18-25 years). Sk197 was dated to AD 689-975 (UBA-11443) and was slightly older (30-40 years) when he died. While multiple osteochondromas were evident throughout his skeleton, they were generally less pronounced than those evident in Sk331. Limb length discrepancy was present in his forearm bones, his sacro-iliac joints displayed ankylosis and he would have had genu valgum during life. Unlike Sk331, he was estimated to have been of roughly average height for the population (166.8 cm). Neither individual appears to have suffered from any tumors that progressed to malignancy4.

R1b1a1b1a1a2c1a1a1a1a1a3a (SNPs: M207; M343; M269; P312; S245; L21; M222; DF106; DF104; DF105; A259; A260)

R1b1a1b1a1a2c1a1a1a1a1a1a (SNPs: M207; M343; M269; P312; S245; L21; M222; DF106; DF104; DF105)