Ancestry deconvolution of Estonian, European and Worldwide genomic layers: a human population genomics excavation
Kuupäev
2022-05-18
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Tänapäeval eeldame sageli, et meie moodne eluviis on minevikust parem, ja et mida kaugemale me ajas tagasi läheme, seda enam heitlesid mineviku inimesed kehvade elutingimuste või küündimatu tehnoloogiaga. Pole üllatav, et ajaloolised ja arheoloogilised uuringud äratavad meist paljude uudishimu – nende tõttu oleme sunnitud oma tänapäevast uskumuste süsteemi ümber kujundama ning jahmuma sellest, kui palju mineviku populatsioonid tegelikult saavutada suutsid. Mineviku inimesed olid organiseerunud ühiskonnaks, nad liikusid, rändasid, jagasid ideid, kultuure ja tehnoloogiaid – ja me leiame ikka veel nende kokkupuudete jälgi. Käesoleva doktoritöö eesmärgiks mineviku kokkupuudete jälgede uurimine geneetilistes andmetes.
Populatsioonide kokkupuudet nimetatakse segunemissündmuseks, mis tekitab segunenud populatsioone. Lähenemisviisiga, mida nimetatakse põlvnemise lahtiharutamiseks (Ancestry Deconvolution, AD), saame segunenud grupi geneetilist mosaiiki analüüsida, ajades segunemise osaliste jälgi, ja segunemissündmust täpsemalt iseloomustada.
AD lähenemisviiside seas on meetodid, mida nimetatakse lokaalse põlvnemise tuletamiseks (Local Ancestry Inferences, LAI), mis võimaldavad tuletada antud päriliku lookuse põlvnemist. Sellistel kõrge lahutusastmega tuletustel on piirangud, mis mõnel juhul LAI tööriistade jõudlust tugevalt piiravad. Seega, rakendades LA-d segunenud populatsioonil, mida iseloomustab põlvnemine eri maailmajagudest, saame keskenduda tundmatute mineviku demograafiliste sündmuste avastamisele, kuid LA kasutamine maailmajao sisestel segunemistel, näiteks Euroopa populatsioonidel, nõuab metodoloogilist lähenemist, mis on kujundatud nii, et see võtab kõigepealt arvesse LA piiranguid.
Lõpuks saame kasutada AD ja LAI lähenemisviise, et esitada küsimusi väljaspool demograafilisi uuringuid. Teatud fenotüübi väljakujunemise tõenäosust on võimalik osaliselt ennustada polügeensete skooride (Polygenic Scores, PS) abil. Kuid genoomile mõjuv tohutu hulk muutujaid on populatsioonispetsiifilised ja tuletused pole eriti ühelt populatsioonilt teisele üle kantavad, mis takistab PS-i rakendatavust vähem uuritud või segunenud populatsioonidele.
Ma esitlen kolme uuringut, mis arutlevad AD ja LAI võimaluste ja piirangute üle. Uurisin segunemissündmust, milles said kokku väga erinevad populatsioonid eri maailmajagudest; väikesel skaalal segunemissündmuste, näiteks Euroopa rühmade puhul, lahtiharutamise piiranguid; ja lõpuks rakendasin kogutud teadmisi, ületamaks polügeensete skooride kasutamise piiranguid segunenud populatsioonidel.
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 organised, 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 characterise 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 characterised 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.
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 organised, 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 characterise 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 characterised 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.
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Märksõnad
descent, establishment of filiation, population genetics