High-coverage paleo-genome research identifies a pathogenic mutation on EXT1 in a Qing-period Chinese individual with multiple osteochondromas

PRJCA069372 Original Paper / DOI2026-07-251 samples (study)

AI interpretationAI-generated

清代山东一例骨软骨瘤患者古DNA揭示EXT1致病突变。

Researchers sequenced the petrous bone of a Qing-period individual from Shandong, China, suspected of having multiple osteochondromas. With high coverage (27x), they found a heterozygous EXT1 mutation (c.791T>C; p.Leu264Pro) at 17x depth. This same mutation appears in an unrelated modern Latin American patient. Protein structure analysis suggests the mutation damages EXT1 function. This confirms the ancient diagnosis genetically and links past and present cases.

A pathogenic EXT1 mutation (c.791T>C; p.Leu264Pro) was found in a Qing-period Chinese individual.
The same mutation is present in an unrelated modern Latin American patient, expanding the known mutation spectrum.
3D protein modeling indicates the mutation causes structural and functional damage to EXT1.

Sample interpretation

The study analyzed one ancient individual from Qing-period Shandong, China. The sample yielded a male Y-chromosome haplogroup O-TYT63912 and mitochondrial haplogroup G1c. Whole-exome sequencing achieved 27.172x mean coverage, with the mutation covered at 17x. This high-quality ancient DNA allowed reliable genetic diagnosis, showing the power of paleogenomics for rare diseases.

For genealogy enthusiasts

For ancestry enthusiasts, this shows ancient DNA can diagnose genetic diseases in historical individuals. It connects a Qing-period Chinese person to a modern patient via a shared EXT1 mutation, highlighting how paleogenomics illuminates disease history and human migration.

Abstract

Multiple osteochondromas (MO) is a rare bone disease with variable manifestations that make it difficult to distinguish from phenotypically similar diseases, both morphologically and radiologically. As a monogenic disorder associated with mutations in EXT1 or EXT2, ancient DNA analysis can provide genetically confirmed diagnoses and insights into the pathogenesis of suspected cases. To further investigate a previously reported suspected MO case from Qing-period Shandong, China, we generated ancient whole-exome sequencing data from the individual’s petrous bone, yielding a mean sequencing coverage of 27.172×. We identified a pathogenic heterozygous mutation in the ligand-binding site Rossmann-2 subdomain of EXT1 (c.791T > C; p.Leu264Pro) with a sequencing depth of 17×, a mutation also found in an unrelated modern Latin American patient. Additionally, by predicting and analyzing the 3D structure of the EXT1 protein, we detected structural and functional damage. Our findings expand the known spectrum of EXT1 mutations and enhance the comprehensive genotype–phenotype map of rare MO, providing insights into its genetic pathology from a historical perspective. Furthermore, this research expands the understanding of disease landscapes in Northern China, both paleopathologically and paleogenetically.

Samples & Data on TheYtree

1samples on site

1Y haplogroup resolved

Paternal (Y-DNA) Haplogroups

Haplogroup	Samples
O-TYT63912	1

Maternal (mtDNA) Haplogroups

G1c · 1

Sample Highlights More samples →

Sample	Y-DNA	mtDNA	Culture / Period
IC2613(HRR3435266)-清代	O-TYT63912	G1c	· 清代 Qing Dynasty