Resumen de Population genetics of Copy Number Variants: the case of the Romani population
- español
Mucha información de la población Romaní ha sido recolectada, incluyendo investigación histórica, lingüística y genética. Aunque los análisis de genomas completos en esta población solo empezaron recientemente, hasta ahora la mayoría de los estudios que usan datos genéticos solo usan polimorfismos de nucleótido único (SNPs). Este estudio se dirige, por primera vez, a analizar las variantes del número de copias (CNVs) de genomas completos en los Romaní. Usando las deleciones, reconstruimos las relaciones de los Romaní con las poblaciones relacionadas (Euroasiática y Sudasiática) y destacamos la diferenciación entre ellas. Además, una mayor presencia de deleciones en genes intolerantes a la pérdida de función en los Romaní indica una relajación de la selección natural por aquellas variantes posiblemente deletéreas. Finalmente, los Romaní muestran una sobrerrepresentación de esas deleciones en genes relacionados a características del sistema nervioso y, asimismo, el linkage disequilibrium con SNPs en genes con importancia biomédica previamente analizados en los Romaní podría sugerir una acción sinérgica de CNVs y SNPs en consecuencias fenotípicamente relacionadas.
- English
Studying human population genetics, thus focussing on the variation at the genetic level among humans from worldwide locations and the processes occurred to produced it, provided many insights for the evolutionary history of Homo sapiens and its ancestors. Indeed, during the history towards modern humans as well as after their colonization of the Earth, individuals within populations faced different conditions and stressors from the wide set of environments they inhabited and favourable genetic features in each circumstance were more likely to persist and pass to the next generations. Random changes of allele frequencies play a role in defining the destiny of variants within populations and different populations can experience more or less drastic variations of these distribution changes. Human populations, however, are not closed entities reacting strictly to the environment they experience, instead they move, fragment and mix with each other. All these processes help reshuffling bits of ¿variability sets¿ of each contributor, which can have functional consequence (and be more or less prone to pass on subsequent generations) or be neutral but, that if traced back, can reveal the past histories of human groups.
Historically, human population genetics has been addressed predominantly by leveraging single nucleotide polymorphisms (SNPs) as the marker of choice, this allowed a wide evolution and refinement of both detection and inference techniques. Nonetheless, although only recently, the contribution of copy number variants (CNVs) to human differentiation, evolution and health has been largely recognised, sparking the interest in what can be inferred also including this type of variants. CNVs in fact, encompassing larger stretches of nucleotides than SNPs and thus are responsible for a higher amount of nucleotide variation. As a result, their impact could be stronger than point mutations, playing a role in the biology and evolution of humans.
In this PhD thesis the interesting features of CNVs are analysed for the first time within the context of a historically isolated and underrepresented population, the Romani. The study poses its foundations on a double purpose: one is assessing the information that can be detected, using CNVs, in a population whose peculiar iii demographic history has been addressed using classical genetic markers; the second is exploiting this new source of information in such an interesting population scenario, to investigate new putative information previously undescribed. The first instance indeed can reveal the potential of CNVs to cover (or not) known details of Romani and allowing an evaluation of the informative power of these markers within an underrepresented group. The second aspect focusses more on the known features of CNVs to explore further the genetic information in Romani that might have escaped research with classical markers, making them suitable and interesting for advancing the knowledge within this context.
In this thesis, we analysed the population genetics of the Romani population using CNVs and were able to reconstruct the relationships among the analysed populations using deletions. We highlight a consistent pattern of variant accumulation in the Romani which may be explained by their history, pointing towards a putative lower constrain in Romani for the accumulation of deletions at untranslated portions of the genome, within genes intolerant to loss of function.
