Exploring genetic connections through time

Silvia Gonzalez, Professor in Quaternary Geology and Geoarchaeology from the School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool was awarded funding from the Paget's Association for her study, 'Contributions of ancient genome DNA, molecular and isotopic studies to aid the understanding of Paget´s disease during the medieval period at Norton Priory. [2019-2023]

Medieval Paget´s Disease

Writing in 2020, Professor Silvia Gonzalez explains the research.

Background

Since 2015, research exploring Paget’s disease at Medieval Norton Priory in Runcorn, Cheshire, has been a fascinating journey, providing new insights into the development of Paget’s disease in the past. Originally, only six of the medieval skeletons were recognised to have skeletal signs of Paget’s disease (5%). Further skeletons have been identified during a phase of research completed during the last three years. This has brought the number of those affected up to 46 out of 130 (35%). This is a remarkable increase and has not been seen before in an archaeological collection.

In collaboration with experts from Liverpool John Moores, Nottingham, East Anglia, Leicester and Liverpool Universities, and with the partnership of Norton Priory Museum, this archaeological collection has been the subject of further detailed evaluation. To date, the original six and an additional twelve skeletons with Paget’s disease have been the subject of detailed analysis. Full macroscopic and x-ray examination has identified that up to 75% of individual skeletons studied are affected by the condition, suggesting an early on‑set in young adulthood.

CT and Micro-CT imaging have complemented the diagnosis of Paget’s in these skeletons. Radiocarbon dating has identified that Paget’s disease has been present at Norton for over 400 years during Medieval times (AD 1020‑1479). By studying their teeth (stable isotope studies) it was identified that these individuals had a mainly marine based diet and were born and lived locally in the North West of England, a recognised hotspot of modern Paget’s disease. Interestingly, molecular research has identified abnormalities in the SQSTM1 gene or p62 protein in the Norton skeletons, suggesting the presence of an ancient precursor of contemporary Paget’s disease, the first to be reported in an archaeological collection.

In this new research phase (2020 onwards), in collaboration with the Ancient Genomics Laboratory from the Frances Crick Institute in London, the researchers propose to extend their analyses to fourteen new selected skeletons with Paget’s disease from the collection, plus one healthy individual for comparison. The researchers want to characterise, in detail, these medieval individuals and their lifestyles. The study will incorporate the following:

Radiocarbon dating – This is a technique used to learn the age of the skeletons.

Stable isotope studies – Isotopes are present everywhere, but the balance (or ratios) in which different isotopes of the same elements occur, varies between different substances. The isotopes that are in the food we eat and the water we drink are incorporated into all our body tissues, including our skeleton. By measuring the ratios of different isotopes in bones or teeth and using scientific knowledge about how they occur in nature to trace them back to the sources that they came from, scientists can learn many things about an individual, such as what their diet was like and the environment they grew up in.

Paleodiet analysis – This will investigate what type of food was eaten.

Paleoproteomics - A technique which involves protein sequencing using mass spectrometry. This allows analysis of bone samples at the molecular level, by extracting proteins from the ancient bone cells. This offers an insight into the biology of the cell when it was alive many hundreds of years ago.

Exploring aDNA - For the first time the full ancient genome information (aDNA) will be obtained for a medieval population in the UK to explore their genetic connections through time.

Comparing the ancient with the modern

Professor Gonzalez remarked, “This research will enhance our understanding of this ancient form of Paget’s disease and enable comparison with modern individuals affected by the condition.”

The Paget’s Association will watch with interest this developing project, which may lead to information crucial to helping doctors understand the fall in incidence of modern‑day Paget’s disease, which has been observed over the past few decades.