47,XXY karotype, Klinefelter's syndrome identified in a medieval skeleton
In a paper published in the Lancet "A 1000-year-old case of Klinefelter's syndrome diagnosed by integrating morphology, osteology, and genetics" the authors conclude the individual had Klinefelter's syndrome (an extra X chromosome) identified by a probabilistic assignment based on a number of sequencing reads, and backed by morphological/osteological examination of the bones (Klinefelterâs are âgenetically maleâ, X is not a âfemaleâ chromosome, it is present in everyone, but an extra X chromosome = XXY, can present a number of identifiable medical conditions, see  https://www.nhs.uk/conditions/klinefelters-syndrome for more)
Yet another reason for more - and more novel - DNA studies on archaeological skeletons.
 https://doi.org/10.1016/S0140-6736(22)01476-3  (original article has far more supplementary data + figs)
""""" The skeleton of a human being buried over 1000 years ago, in the medieval archaeological site of Torre Velha, in north-eastern Portugal, was referred to us for analysis and investigation (appendix).
On examination, we found the outstandingly well preserved skeleton of an adult who was likely to have been more than 25 years old at the time of death. The person was approximately 1¡80 m tall. Notably, out of the six skeletons examined, where height could be ascertained, this individual was the tallest (appendix). Based on pelvic morphology and metric analysis of the skeleton, we concluded that the individual was a man. However, the bi-iliac width of our person was 289 mm, considerably larger than the average width previously reported for ancient Portuguese men (mean 261¡8 mm; SD=13¡4; Student's t test: t=22¡6944; df=124; p<0¡001). Additionally, the individual's teeth were worn asymmetrically, indicating probable malocclusion of the jaw and maxillary prognathism (figure; appendix). Bone densitometry analysis showed normal bone mineral density values (0¡792â0¡999 g/cm2).
Genetic analysis was undertaken using a variety of different methodologiesâincluding the calculation of X chromosome to Y chromosome autosome ratios (0¡902 and 0¡298, respectively), X chromosome and Y chromosome dosages (approximately 2 and 1, respectively), and X chromosome heterozygosity (approximately 0¡2). We also determined the Y chromosome haplogroup to be R1b-P310 (R1b1a1b1a1), a frequent western-European and pan-European lineage, in accordance with the individual's Iberian genetic ancestry (appendix).
Furthermore, using a novel Bayesian method, allowing us to probabilistically assign individuals to karyotypes based on the number of sequencing readsâor DNA fragments sequencedâmapping to the X, Y, or autosomal chromosomes, we concluded our individual's karyotype to be 47,XXY, and rejected models of contamination of XXY and XX or XY (figure; appendix). The closeness of the observed position of the studied individual and theoretical position for an XXY karyotype (figure) strongly agrees with our posterior probability of approximately 1 for this individual having a Klinefelter's syndrome karyotype. Considering the morphological findingsâspecifically the height, the bi-iliac width, the possible jaw malocclusion, and the maxillary prognathismâthe genetic findingsâindicating a karyotype of 47,XXYâwe concluded that the studied individual had Klinefelter's syndrome."""""
Prof ClĂĄudia Umbelino, PhD
Prof AntĂłnio Amorim, PhD
Prof Pedro C Carvalho, PhD
Published: August 27, 2022DOI: https://doi.org/10.1016/S0140-6736(22)01476-3