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

Abstract

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes (COL1A1, COL2A1, KMT2D, FLNB, ATR, TRIP11, PCNT) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification.

Who are we as historical beings? Shaping identities in light of the archaeogenetics ‘revolution’

“…The discussion started as a reaction to a paper signed by Sanchita Bhattacharya and colleagues (2018) which claimed that the phys ical appearance of a childmummy reportedly discovered in 2003 in the Chilean desert was due to 'mutations linked with dysplasia'. The news led to several reactions on Twitter, an opinion piece by Cristina Dorador (2018) in Etilmercurio, an online Chilean science news website, a paper published by eight bioarchaeologists (Halcrow et al 2018), and multiple texts in Forbes, Live Science, New York Times and even in the UK Daily Mail. Among the critiques were that 'there was no scientific rationale to undertake genomic analyses of Ata because the skeleton is normal', its context was problem atic (it came from a private collection), the destructive sampling of human remains, and that DNA analyses are costly, so they should be employed wisely (Halcrow et al 2018).…”

Sensationalism and speaking to the public: Scientific rigour and interdisciplinary collaborations in palaeopathology

“…Where such publications are methodologically sound, following accepted paleopathological and anthropological standards, and appropriately interpreted in the historical and archaeological context, they help to advance a meaningful understanding of bioarchaeology in the public sphere (see Appleby et al, 2014Appleby et al, , 2015Belcastro et al, 2011;Kacki et al, 2018). However, some appear to have dismissed or only superficially engaged with established methodological protocols for the identification of disease in skeletal or mummified human remains (Charlier et al, 2016(Charlier et al, , 2019Bhattacharya et al, 2018, Loynes et al, 2018. Frequently these manuscripts are authored by scholars with little understanding of the limitations of paleopathology and appear to have gone through peer review without input from paleopathologists or archaeologists.…”

How the Atacama Skeleton Might Advance Discussion of Responsible Conduct of Research Responsibilities

“…The recent controversy surrounding research by Bhattacharya et al (2018) on the skeletal remains of what turned out to be a human fetus of Chilean descent has clouded several important issues in the responsible conduct of research. A focus on the issue of whether the study qualified as human subjects research has obscured the more fundamental issue of the ethical conduct of scientific research in general, and the duties of researchers to proactively assure ethical chain of custody for samples.…”