NEW YORK (GenomeWeb) – A team of researchers at Stanford University and the University of California, San Francisco has sequenced the genome of an unusual-looking mummified skeleton found in Chile, identifying several novel mutations in genes that have been previously linked to skeletal malformations.
In 2003, a mummified humanoid skeleton was found in an abandoned mining town in the Atacama region of Chile. Nicknamed Ata, the specimen had a peculiar phenotype: a height of 6 inches, fewer ribs than expected, a lengthened cranium, and an estimated bone age of six to eight years.
For the study, published today in Genome Research, senior author Garry Nolan and his team purified genomic DNA isolated from the specimen and performed whole-genome sequencing in order to determine the possible genetic drivers of its morphology.
Based on DNA analysis, the team had previously reported that the specimen — which some had speculated to be a non-human primate, or even an alien — was human, with an estimated bone age of six to eight years at death. Further DNA analysis revealed that the Ata specimen's mitochondrial B2 haplotype group had significant overlap with the South American population.
Since the individual's phenotype may be connected to a sex-linked disease, the team investigated its sex, using a technique that incorporated the ratio of sequence alignment to the Y and X chromosomes, as well as the cytosine deamination signature of ancient DNA. The Ata specimen showed a very small fraction of alignment to the Y chromosome, and no single read mapped to the SRY gene region on Chromosome Y. Together, the findings indicated that Ata was female.
In order to assess the specimen's genetic ancestry, the team merged its genotype data into a reference set of five super populations of the 1000 Genomes Project, using single nucleotide polymorphism sites present in the Ata genome. They found that the Ata specimen lay in the range of admixed populations of Mexican, Colombian, and Peruvian ancestry.
Performing a principal component analysis on the specimen, the team also demonstrated that its closest living relatives were from the Andean region belonging to the Chilean Chilote population. The results also suggest that Ata is admixed with a large population of European, East Asian, and other minor populations, further confirming that Ata is a modern human specimen with a range of complex admixture events.
In order to identify variants in genes that are potentially linked with diseases, the team focused on functionally important variants from over 2.7 million high-quality single nucleotide variants. After performing a series of filtering procedures, Noland and his team found 54 coding regions predicted to be detrimental with gene-based functional annotation.
The team then analyzed the 54 coding regions with phenotype enrichment, using the Human Phenotype Ontology database (HPO), and found that the majority of the phenotypes were bone-associated, including 11 pairs of ribs, joint dislocation, and broad long bones. The diseases identified in the genes included scoliosis, dwarfism, and osteochondrodysplasia.
The team found multiple novel missense SNVs that had not been previously described in genes that code for collagen, filamin B, lysine-specific methyltransferase, thyroid hormone receptor interactor 11, ataxia telangiectasia and Rad3-related protein, and pericentrin.
The genes were previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and skeletal dysplasia. The researchers therefore believe that the combination of gene mutations affecting bone development and ossification ultimately led to the infant's peculiar phenotype.
"Taken together, it is entirely plausible that the chance combination of multiple known mutations and novel SNVs identified ... may explain Ata's small stature, inappropriate rib count, abnormal cranial features, and perceived advanced bone age," the researchers noted. Because of the specimen's size and the severity of the mutations, the team inferred that the skeleton is from a preterm infant.