Doctoral defence: Ludovica Molinaro “Ancestry deconvolution of Estonian, European and Worldwide genomic layers: a human population genomics excavation”

On 20 June at 16:00 Ludovica Molinaro will defend her doctoral thesis “Ancestry deconvolution of Estonian, European and Worldwide genomic layers: a human population genomics excavation” for obtaining the degree of Doctor of Philosophy (in Gene Technology).

Supervisors:
Luca Pagani, University of Tartu
Francesco Montinaro, University of Tartu
Mait Metspalu, University of Tartu

Opponent:
Dr. Priya Moorjani, University of California (USA)

Summary
Nowadays, we often assume that our modern way of life is better than the past ones, and the more we go back in time, the more the past humans struggled with poor living conditions or unperforming technologies. It is no surprise that historical and archaeological studies tackle the curiosity of many of us: with them we are forced to reshape our modern belief system and gasp before how much past populations could in fact achieve. People in the past were organized, they moved, travelled, shared ideas, cultures and technologies: and we can still find traces of their encounters. This thesis aims to look at the residual traces of past encounters through the genetic data.

The encounter of populations is referred to as admixture event and creates admixed populations. With an approach called ancestry deconvolution (AD) we can analyse the genetic mosaic of an admixed group, tracing the admixing contributors and further characterize the admixing event.

Within the AD approaches, there are the methods referred to as Local Ancestry Inferences (LAI) that allows to infer which ancestry falls within a given inherited locus. Such a fine level of inferences come with constraints, highly limiting the LAI tools performances in some cases. In turn, while performing LA on an admixed population characterized by worldwide ancestries we can focus on discovering unknown past demographic events, applying LA on sub-continental admixtures, such as European populations, requires a methodological approach that must be designed to comprehend the LA limitations first.

Eventually, we can leverage AD and LAI to ask questions beyond the realm of demography studies. It is possible to partially predict the probability of developing a certain phenotype with the Polygenic Scores (PS). However, the vast number of variables acting upon the genome are population-specific, and the inferences are hardly transferable from one population to another, hindering the application of PS to understudied or admixed populations.

I present three studies that discuss the potentialities and limits of AD and LAI. I studied an admixture event where worldwide, highly divergent populations came together; the limitations in deconvoluting fine-scale admixture events, such as in European groups; and finally I applied the built knowledge to overcome the limitations in applying Polygenic Score on admixed populations.

The defence can be also followed in Zoom (Meeting ID: 955 7651 0272, Passcode: 842234).