Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA.

Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice.

Genomic analyses of hair from Ludwig van Beethoven.

Ludwig van Beethoven (1770-1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven's genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven's hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beethoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven's patrilineal ancestry.

Ancient DNA reveals admixture history and endogamy in the prehistoric Aegean.

The Neolithic and Bronze Ages were highly transformative periods for the genetic history of Europe but for the Aegean-a region fundamental to Europe's prehistory-the biological dimensions of cultural transitions have been elucidated only to a limited extent so far. We have analysed newly generated genome-wide data from 102 ancient individuals from Crete, the Greek mainland and the Aegean Islands, spanning from the Neolithic to the Iron Age. We found that the early farmers from Crete shared the same ancestry as other contemporaneous Neolithic Aegeans. In contrast, the end of the Neolithic period and the following Early Bronze Age were marked by 'eastern' gene flow, which was predominantly of Anatolian origin in Crete. Confirming previous findings for additional Central/Eastern European ancestry in the Greek mainland by the Middle Bronze Age, we additionally show that such genetic signatures appeared in Crete gradually from the seventeenth to twelfth centuries BC, a period when the influence of the mainland over the island intensified. Biological and cultural connectedness within the Aegean is also supported by the finding of consanguineous endogamy practiced at high frequencies, unprecedented in the global ancient DNA record. Our results highlight the potential of archaeogenomic approaches in the Aegean for unravelling the interplay of genetic admixture, marital and other cultural practices.