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Ancestry and Pathology in King Tutankhamun's Family Ancestry and Pathology in King Tutankhamun's Family Zahi Hawass; Yehia Z. Gad; Somaia Ismail; et al. JAMA. 2010;303(7):638-647 (doi:10.1001/jama.2010.121) Online article and related content current as of October 14, 2010. http://jama.ama-assn.org/cgi/content/full/303/7/638 Supplementary material eSupplement http://jama.ama-assn.org/cgi/content/full/303/7/638/DC1 Correction Contact me if this article is corrected. Citations This article has been cited 7 times. Contact me when this article is cited. Topic collections Neurology; Neurogenetics; Movement Disorders; Rheumatology; Musculoskeletal Syndromes (Chronic Fatigue, Gulf War); Malaria; Genetics; Genetic Disorders; Humanities; History of Medicine; Infectious Diseases Contact me when new articles are published in these topic areas. Related Articles published in King Tutankhamun, Modern Medical Science, and the Expanding Boundaries of the same issue Historical Inquiry Howard Markel. JAMA. 2010;303(7):667. Related Letters King Tutankhamun’s Family and Demise Eline D. Lorenzen et al. JAMA. 2010;303(24):2471. Brenda J. Baker. JAMA. 2010;303(24):2471. James G. Gamble. JAMA. 2010;303(24):2472. Irwin M. Braverman et al. JAMA. 2010;303(24):2472. Christian Timmann et al. JAMA. 2010;303(24):2473. Subscribe Email Alerts http://jama.com/subscribe http://jamaarchives.com/alerts Permissions Reprints/E-prints [email protected] [email protected] http://pubs.ama-assn.org/misc/permissions.dtl Downloaded from www.jama.com by guest on October 14, 2010 ORIGINAL CONTRIBUTION Ancestry and Pathology in King Tutankhamun’s Family Zahi Hawass, PhD Context The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th Yehia Z. Gad, MD dynasties, spanned the mid-16th to the early 11th centuries BC. The late 18th dy- Somaia Ismail, PhD nasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, Rabab Khairat, MSc the exact relationships between some members of the royal family, and possible ill- Dina Fathalla, MSc nesses and causes of death have been matters of debate. Naglaa Hasan, MSc Objectives To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and Amal Ahmed, BPharm to search for pathological features attributable to possible murder, consanguinity, in- Hisham Elleithy, MA herited disorders, and infectious diseases. Markus Ball, MSc Design From September 2007 to October 2009, royal mummies underwent de- tailed anthropological, radiological, and genetic studies as part of the King Tut- Fawzi Gaballah, PhD ankhamun Family Project. Mummies distinct from Tutankhamun’s immediate lineage Sally Wasef, MSc served as the genetic and morphological reference. To authenticate DNA results, ana- Mohamed Fateen, MD lytical steps were repeated and independently replicated in a second ancient DNA labo- ratory staffed by a separate group of personnel. Eleven royal mummies dating from Hany Amer, PhD circa 1410-1324 BC and suspected of being kindred of Tutankhamun and 5 royal mum- Paul Gostner, MD mies dating to an earlier period, circa 1550-1479 BC, were examined. Ashraf Selim, MD Main Outcome Measures Microsatellite-based haplotypes in the mummies, gen- erational segregation of alleles within possible pedigree variants, and correlation of Albert Zink, PhD identified diseases with individual age, archeological evidence, and the written his- Carsten M. Pusch, PhD torical record. HE 18TH DYNASTY (CIRCA 1550- Results Genetic fingerprinting allowed the construction of a 5-generation pedigree 1295 BC) of the New King- of Tutankhamun’s immediate lineage. The KV55 mummy and KV35YL were identi- fied as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses dom (circa 1550-1070 BC) was (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation one of the most powerful royal of malformations in Tutankhamun’s family was evident. Several pathologies including Thouses of ancient Egypt. The pharaoh Köhler disease II were diagnosed in Tutankhamun; none alone would have caused death. Akhenaten, who ruled from circa 1351 Genetic testing for STEVOR, AMA1, or MSP1 genes specific for Plasmodium falcipa- to 1334 BC, is considered one of the rum revealed indications of malaria tropica in 4 mummies, including Tutankhamun’s. most controversial of the Egyptian pha- These results suggest avascular bone necrosis in conjunction with the malarial infec- raohs, because his attempt to radically tion as the most likely cause of death in Tutankhamun. Walking impairment and ma- transform traditional religion affected larial disease sustained by Tutankhamun is supported by the discovery of canes and all facets of society and caused great an afterlife pharmacy in his tomb. turmoil. Conclusion Using a multidisciplinary scientific approach, we showed the feasibility Akhenaten’s eventual successor, Tut- of gathering data on Pharaonic kinship and diseases and speculated about individual ankhamun, is probably the most fa- causes of death. mous of all pharaohs, although his ten- JAMA. 2010;303(7):638-647 www.jama.com ure was brief. He died in the ninth year Author Affiliations: Supreme Council of Antiquities, (Drs Gaballah and Fateen and Ms Wasef); Department of his reign, circa 1324 BC, at age 19 years. Cairo, Egypt (Dr Hawass and Mr Elleithy); National of Radiodiagnostics, Central Hospital Bolzano, Bol- Research Center, Cairo, Egypt (Drs Gad, Ismail, and Amer zano, Italy (Dr Gostner); Department of Radiology, Kasr Little was known of Tutankhamun and and Mss Hasan and Ahmed); Ancient DNA Laboratory, Al Ainy Faculty of Medicine, Cairo, Egypt (Dr Selim); and his ancestry prior to Howard Carter’s Egyptian Museum, Cairo, Egypt (Drs Gad and Ismail and Institute for Mummies and the Iceman, EURAC, Bol- Mss Fathalla, Khairat, Hasan, and Ahmed); Institute of zano, Italy (Dr Zink). discovery of his intact tomb (KV62) in Human Genetics, Division of Molecular Genetics, Uni- Corresponding Author: Carsten M. Pusch, PhD, Institute versity of Tübingen, Tübingen, Germany (Ms Khairat, of Human Genetics, Division of Molecular Genetics, Uni- For editorial comment see p 667. Mr Ball, and Dr Pusch); Learning Resource Center, Kasr versity of Tübingen, Wilhelmstraße 27, D-72074, Tübin- Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt gen, Germany ([email protected]). 638 JAMA, February 17, 2010—Vol 303, No. 7 (Reprinted with Corrections) ©2010 American Medical Association. All rights reserved. Downloaded from www.jama.com by guest on October 14, 2010 ANCESTRY AND PATHOLOGY IN KING TUTANKHAMUN’S FAMILY the Valley of the Kings in 1922, but METHODS Sixteen Y-chromosomal short tan- his mummy and the priceless trea- Mummies dem repeats (DYS456, DYS389I, sures buried with him, along with other In addition to Tutankhamun, 10 mum- DYS390, DYS389II, DYS458, DYS19, important archeological discoveries mies possibly or definitely closely re- DYS385, DYS393, DYS391, DYS439, of the 20th century, have provided sig- lated in some way to Tutankhamun were DYS635, DYS392, Y-GATA-H4, nificant information about the boy pha- chosen for this 2-year project; of these, DYS437, DYS438, DYS448) were am- raoh’s life and family. the identities were certain for only 3. In plified according to the manufactur- Because Tutankhamun died so young addition to these 11 mummies, 5 other er’s protocol using the AmpF\STR Yfiler and left no heirs, numerous specula- royal individuals dating to the early New PCR amplification kit (Applied Biosys- tions on familial disease have been made. Kingdom were selected that were dis- tems, Foster City, California). The Iden- The presence of disease is further sup- tinct from the putative members of the tifiler kit and the AmpF\STR Minifiler ported by numerous reliefs, statuettes, Tutankhamun lineage. These 5 mum- kit (Applied Biosystems) were used and other sculptures of Akhenaten and mies were used as a morphological (ex- for amplification of 8 polymorphic mi- his family dating from the Amarna pe- cluding Ahmose-Nefertari) and genetic crosatellites of the nuclear genome riod (circa 1353-1323 BC). These arti- (excluding Thutmose II) control group. (D13S317, D7S820, D2S1338, D21S11, facts show the royalty of that era as hav- All mummies are listed in TABLE 1, and D16S539, D18S51, CSF1PO, FGA). ing a somewhat androgynous appearance full-body computed tomography recon- To test for Plasmodium falciparum or a bizarre form of gynecomastia. Spe- structions of the mummies are avail- DNA, PCR primers were designed that cific diseases that have been suggested able in the online feature at http://www specifically amplify small subtelo- to explain this appearance include .jama.com. meric variable open reading frame Marfan syndrome, Wilson-Turner X- (STEVOR), apical membrane antigen 1 linked mental retardation syndrome, Radiology (AMA1), and merozoite surface pro- Fröhlich syndrome (adiposogenital dys- All of the mummies, except for that of tein 1 (MSP1) gene fragments with sizes trophy), Klinefelter syndrome, andro- Ahmose-Nefertari, were scanned using a of 100 to 250 base pairs (bp). PCR prod- gen insensitivity syndrome, aromatase multidetectorcomputedtomographyunit ucts and cloned DNA fragments were excess syndrome in conjunction with (Somatom Emotion 6; Siemens Medical sequenced by the Sanger method sagittal craniosynostosis syndrome, or Solutions, Malvern, Pennsylvania) in- (eAppendix). Purified amplicons were Antley-Bixler syndrome or a variant form stalled on a truck. The tomography unit run on a genetic analyzer (ABI Prism of that syndrome.1-4 However, most of the was used to examine the mummy of 3130, Applied Biosystems). Microsat- disease diagnoses are hypotheses de- Tutankhamun and those of the 2 wom- ellites were interpreted with Data rived by observing and interpreting ar- en from tomb KV35 in Luxor as well as Collection Software version 3.0 and tifacts and not by evaluating the mum- the rest of the mummies at the Egyptian GeneMapper ID version 3.2 (Applied mified remains of royal individuals apart Museum in Cairo (eAppendix, avail- Biosystems).
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