ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 14.17 | DOI: 10.1530/ey.16.14.17

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia

Bhattacharya S, Li J, Sockell A, Kan MJ, Bava FA, Chen SC, Avila-Arcos MC, Ji X, Smith E, Asadi NB, Lachman RS, Lam HYK, Bustamante CD, Butte AJ & Nolan GP


Institute for Computational Health Sciences, University of California San Francisco, San Francisco, California, USA


To read the full abstract: Genome Res 2018;28:423–431

The discovery of a mummified humanoid female skeleton on a shelf in a building in La Noria, Chile in 2003 created enormous scientific and popular interest. Its highly unusual appearance included a length of only 6 inches despite a bone age of 6–7 years old, marked turricephaly (a cone-shaped top of the skull), and reduced number of ribs bilaterally. See photographs at: https://genome.cshlp.org/content/28/4/423/F1.expansion.html.

This extraordinary phenotype led to wide and even bizarre speculation about its origin. The 2013 documentary film ‘Sirius’, based on UFO theorist Steven Greer’s book, claimed that this specimen represented evidence of alien life!

Here, we read that science has come to the rescue. From only one cubic millimetre of bone, the US research team extracted high quality DNA and performed whole-genome sequencing (WGS). They confirmed that this was a modern Chilean female and found multiple mutations in many genes with known links to bone development and ossification disorders and musculoskeletal abnormalities, including: COL1A1 (Ehlers-Danlos syndrome and osteoporosis), COL2A1 (various osteochondrodysplasias), KMT2D (Kabuki syndrome), FLNB (ectopic and premature ossification), ATR (Seckel syndrome), TRIP11 (achondrogenesis), and PCNT (microcephalic osteodysplastic primordial dwarfism type II, MOPDII). This study shows that WGS can bring a powerfully scientific approach to the understanding of archaeological and anthropological history, in the same way as WGS is unearthing the diagnosis in our clinically undiagnosed patients.

A key remaining question is whether this fetal specimen resulted from a statistically highly extreme coincidence of multiple known and novel mutations. Alternatively, the authors speculate that the discovery site, La Noria, an abandoned nitrate mining town in the Atacama Desert, points to a possible role for prenatal nitrate exposure as a possible cause of multiple de novo mutations.