March 22, 2018 - In 2003, scientists made a surprising discovery of a 6-inch mummified humanoid skeleton in the Atacama region of Chile with an estimated bone age of about 6-8 years old at the time of death. The specimen's exceptionally small stature and multiple skeletal abnormalities, including a cone-shaped skull led to widespread speculation on its origin. In a study published today in Genome Research, whole genome sequencing of the Atacama (Ata) skeleton offers insights into its ancestry and strange phenotype.

Early analyses revealed that the Ata skeleton contained high-quality DNA that was suitable for modern sequencing technology. "This was an unusual specimen with some fairly extraordinary claims put forward. ... it would be an example of how to use modern science to answer the question "what is it?" says senior author Garry Nolan from Stanford University. Using DNA extracted from the bone marrow, Nolan and his colleagues conducted a whole-genome sequence analysis of Ata.

Sequencing reads were aligned to human and non-human primate reference genomes, including chimpanzee and rhesus macaque, which revealed Ata to be of human origin. Ata's Chilean ancestry was resolved by comparing single nucleotide polymorphisms (SNPs) against a database of known SNPs from diverse geographical populations. The ratio of sequence read alignment to the X and Y Chromosomes revealed that Ata was female.

The researchers next probed for genetic clues that could explain Ata's small stature, multiple bone and skull abnormalities, abnormal rib count, and premature bone age. They found multiple mutations in genes associated with diseases such as dwarfism, scoliosis, and musculoskeletal abnormalities. Surprisingly, Nolan claims Ata's "dramatic phenotype could in fact be explained with a relatively short list of mutations in genes known previously to be associated with bone development."

"This is a great example of how studying ancient samples can teach us how to analyze modern day medical samples" says co-author Atul Butte, UCSF. Future studies employing deeper sequencing and analyses of the novel sequence variations found in Ata may improve our understanding of the functional basis of genetic skeletal disorders.

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Researchers from the University of California, San Francisco, Roche Sequencing Solutions, Stanford University, National Autonomous University of Mexico, Ultra Intelligence Corporation, and Stanford University School of Medicine contributed to this work. The study was supported by the Lucile Packard Foundation for Children's Health, the University of California San Francisco endowment, the Human Frontier Science Program Fellowship, and the Rachford and Carlota A. Harris Professorship.

Media Contacts:

The authors are available for more information by contacting Laura Kurtzman, UCSF Communications (Laura.Kurtzman@ucsf.edu); or Hanae Armitage, Stanford press office (harmitag@stanford.edu); 650-725-5376 [office]).

Interested reporters may obtain copies of the manuscript via email from Dana Macciola, Administrative Assistant, Genome Research (macciol@cshl.edu); +1-516-422-4012).

About the article:

The manuscript will be published online ahead of print on 22 March 2018. Its full citation is as follows: Bhattacharya S, Li J, Sockell A, Kan M, Bava F, Chen, S, Ávila-Arcos M, Ji X, Smith E, Asadi N, Lachman R, Lam H, Bustamante C, Butte A, Nolan G. 2018. Whole genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia. Genome Research doi: 10.1101/gr.223693.117

About Genome Research:

Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress. org .

Genome Research issues press releases to highlight significant research studies that are published in the journal.