The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research.

BACKGROUND: The history of rare diseases is largely unknown. Research on this topic has focused on individual cases of prominent (historical) individuals and artistic (e.g., iconographic) representations. Medical collections include large numbers of specimens that exhibit signs of rare diseases, but most of them date to relatively recent periods. However, cases of rare diseases detected in mummies and skeletal remains derived from archaeological excavations have also been recorded. Nevertheless, this direct evidence from historical and archaeological contexts is mainly absent from academic discourse and generally not consulted in medical research on rare diseases. RESULTS: This desideratum is addressed by the Digital Atlas of Ancient Rare Diseases (DAARD: https://daard.dainst.org ), which is an open access/open data database and web-based mapping tool that collects evidence of different rare diseases found in skeletons and mummies globally and throughout all historic and prehistoric time periods. This easily searchable database allows queries by diagnosis, the preservation level of human remains, research methodology, place of curation and publications. In this manuscript, the design and functionality of the DAARD are illustrated using examples of achondroplasia and other types of stunted growth. CONCLUSIONS: As an open, collaborative repository for collecting, mapping and querying well-structured medical data on individuals from ancient times, the DAARD opens new avenues of research. Over time, the number of rare diseases will increase through the addition of new cases from varied backgrounds such as museum collections and archaeological excavations. Depending on the research question, phenotypic or genetic information can be retrieved, as well as information on the general occurrence of a rare disease in selected space-time intervals. Furthermore, for individuals diagnosed with a rare disease, this approach can help them to build identity and reveal an aspect of their condition they might not have been aware of. Thus, the DAARD contributes to the understanding of rare diseases from a long-term perspective and adds to the latest medical research.

First osteological evidence of severed hands in Ancient Egypt.

For the first time, the severed right hands of 12 individuals have been analysed osteologically. The hands were deposited in three pits within a courtyard in front of the throne room of a 15th Dynasty (c.1640-1530 BC) Hyksos palace at Avaris/Tell el-Dab'a in north-eastern Egypt. Although this kind of practice is known from tomb or temple inscriptions and reliefs from the New Kingdom onwards, this is the first time that physical evidence has been used to learn more about the procedure and the individuals whose hands were taken. Here, we show that the right hands belonged to at least 12 adults, 11 males, and possibly one female. It is unclear if the hands were taken from dead or living individuals. After removing any attached parts of the forearm, the hands were placed in the ground with wide-splayed fingers, mainly on their palmar sides. The osteological analysis not only supports the archaeological interpretation of this evidence but also adds more detail regarding trophy-taking practices in Ancient Egypt.

A critical review of the anthropological and paleopathological literature on osteopetrosis as an ancient rare disease (ARD).

OBJECTIVE: A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology. MATERIALS AND METHODS: Three different approaches are combined: a survey of the last 50 years of bioarchaeological publications; an online search addressing six of the more widely used search engines; macroscopic and radiographic analyses of the human remains from the Neolithic site of Palata 2 (Italy). RESULTS: The combined results of the literature survey and the online search identified six cases of osteopetrosis. The majority of search hits place this disease into differential diagnoses. The investigation of the remains from Palata 2, one of the six cases in literature, indicates a non-specific sclerosis of the cranial vault. CONCLUSIONS: Of the six cases of osteopetrosis, only two, one of the autosomal-recessive type (ARO) and one of the autosomal-dominant type (ADO), are supported by direct osteoarchaeological evidence. Therefore, inaccurate differential diagnoses generate an inflated number of cases in the paleopathological record. SIGNIFICANCE: This reappraisal calls for a more informed and evidence-based approach to osteopetrosis and, more generally, to rare diseases in paleopathology. LIMITATIONS: Lack of specific publications on osteopetrosis; more case studies may be present in "gray literature". SUGGESTIONS FOR FURTHER RESEARCH: Cases of osteopetrosis from archaeological and historical collections as well as medical literature are needed to increase knowledge about this rare disease. More precise differential diagnoses are required, particularly when dealing with rare diseases.

How rare is rare? A literature survey of the last 45 years of paleopathological research on ancient rare diseases.

OBJECTIVE: This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this. MATERIALS: A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus. METHODS: Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage. RESULTS: Studies of ancient rare diseases (ARD) are mostly published as case reports in specialized journals and their number did not benefit from the introduction of biomolecular studies. The higher frequency of cases of achondroplasia suggests that not all rare diseases are equally under-represented. CONCLUSIONS: Rare diseases are still largely under-represented in bioarchaeological literature. Their marginality likely results from a combination of taphonomic, methodological and public visibility factors. SIGNIFICANCE: This article is the first attempt to provide a quantitative assessment of the under-representation of ARD and to outline the factors behind it. LIMITATIONS: Rare diseases are an etiologically heterogeneous group. The number of surveyed journals and articles, as well as targeted diseases might be limiting factors. SUGGESTIONS FOR FURTHER RESEARCH: Increasing collection and dissemination of data on ARD; opening a wide-ranging debate on their definition; implementation of biomolecular studies.

Origins and evolution of the Etruscans' mtDNA.

The Etruscan culture is documented in Etruria, Central Italy, from the 8(th) to the 1(st) century BC. For more than 2,000 years there has been disagreement on the Etruscans' biological origins, whether local or in Anatolia. Genetic affinities with both Tuscan and Anatolian populations have been reported, but so far all attempts have failed to fit the Etruscans' and modern populations in the same genealogy. We extracted and typed the hypervariable region of mitochondrial DNA of 14 individuals buried in two Etruscan necropoleis, analyzing them along with other Etruscan and Medieval samples, and 4,910 contemporary individuals from the Mediterranean basin. Comparing ancient (30 Etruscans, 27 Medieval individuals) and modern DNA sequences (370 Tuscans), with the results of millions of computer simulations, we show that the Etruscans can be considered ancestral, with a high degree of confidence, to the current inhabitants of Casentino and Volterra, but not to the general contemporary population of the former Etruscan homeland. By further considering two Anatolian samples (35 and 123 individuals) we could estimate that the genetic links between Tuscany and Anatolia date back to at least 5,000 years ago, strongly suggesting that the Etruscan culture developed locally, and not as an immediate consequence of immigration from the Eastern Mediterranean shores.