Genomic insights into an underrepresented population : the Romani

La població romaní és el grup ètnic minoritari transnacional més gran d'Europa. Tenen un origen sud asiàtic i, durant la seva diàspora cap a Europa, van experimentar múltiples efectes fundadors i una barreja genètica extensa. En aquesta tesi, l’anàlisi de marcadors genètics autosòmics mostren que tots els romaní comparteixen un component genètic comú del sud d’Àsia, de l’Orient Mitjà i dels Balcans, mentre que els grups romaní de la Península Ibèrica i del Bàltic han tingut una barreja addicional amb les altres poblacions de l'entorn. Després de caracteritzar el seu panorama genètic, l’estudi d’exomes complets de romanís espanyols suggereix que el flux de gens no romanís ha contrarestat l’augment de mutacions deletèries causada pels efectes fundadors. A més, les variants clínicament rellevants es troben tant a haplotips europeus com sud-asiàtics consistent amb l’extensa barreja genètica. Aquest treball representa un pas endavant per entendre de manera exhaustiva la història demogràfica romaní i posa de manifest la necessitat d’estudiar poblacions històricament excloses per poder descriure la variació humana en la seva totalitat.The Romani people are the largest transnational minority ethnic group in Europe. They have a South Asian origin and during their diaspora to Europe, they experienced multiple founder effects and gene flow events. In this thesis, the analysis of genome-wide array data shows that Romani groups share a common South Asian, Middle Eastern and Balkan ancestry, while Iberian and Baltic groups experienced additional admixture with the surrounding non-Roma European populations. After characterising their genetic landscape, the study of whole-exome sequences from Spanish Romani suggests that non-Roma gene flow has counteracted the increase in mutational load caused by the founder effects. In addition, clinically relevant variants are traced back to both European and South Asian ancestral haplotypes consistent with the extensive gene flow. Thus, the present work represents a step forward to comprehensively depict the Romani demographic history and emphasises the need to study other underrepresented and historically excluded populations to fully capture human variation

Population Genetics of the European Roma-A Review

This article belongs to the Special Issue Trends in Population Genetics and Identification—Impact on AnthropologyThe Roma are a group of populations with a common origin that share the Romani identity and cultural heritage. Their genetic history has been inferred through multiple studies based on uniparental and autosomal markers, and current genomic data have provided novel insights into their genetic background. This review was prompted by two factors: (i) new developments to estimate the genetic structure of the Roma at a fine-scale resolution have precisely identified the ancestral components and traced migrations that were previously documented only in historical sources, clarifying and solving debates on the origins and the diaspora of the Roma; (ii) while there has been an effort to review the health determinants of the Roma, the increasing literature on their population genetics has not been subjected to a dedicated review in the last two decades. We believe that a summary on the state of the art will benefit both the public and scholars that are approaching the subject.This work was supported by the Spanish Ministry of Science, Innovation and Universities (MCIU) and the Agencia Estatal de Investigación (AEI) [PID2019-106485GB-I00/AEI/10.13039/501100011033]; and “Unidad de Excelencia María de Maeztu” [AEI, CEX2018-000792-M]

Sequence diversity of the uniparentally transmitted portions of the genome in the resident population of Catalonia

Genomic reference databases of residing populations are available in different countries and regions. Since they represent the whole genetic diversity of a geographical region, they have wide applications, from biomedical studies to forensic identifications. Uniparentally transmitted portions of the genome specifically are highly suitable for kinship analyses, mixed DNA cases and geographical ancestry inferences. We have sampled 808 individuals currently residing in Catalonia within the GCAT cohort, from which we have generated 808 high-quality whole mitochondrial DNA (mtDNA) genomes and 399 sequences of the male-specific part of the Y chromosome (MSY). We observe higher genetic diversity than in classical population genetics datasets. We test the robustness of whole sequences for unequivocal identifications, and we found that they have higher resolution than mitochondrial control region and Y chromosome short tandem repeats (Y-STRs), and that most of the variants they present are at low frequencies, increasing the discrimination capacity between individuals. These results confirm the forensic applicability of whole uniparental sequences and provide one of the largest high-quality reference datasets ever published.This work was supported by the Spanish Ministry of Economy and Competitiveness and Agencia Estatal de Investigación (grant numbers CGL2016–75389-P (MINEICO/FEDER, UE), PID2019–106485 GB-I00/AEI/10.13039/501100011033 (MINEICO), and “Unidad María de Maeztu” (CEX2018–000792-M) to FC and DC; and Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, grant 2017SGR00702). Computing time at Barcelona Supercomputing Centre was granted by Red Española de Supercomputación (BCV-2019–3-00002). NF-P was supported by a FPU17/03501 fellowship. This study makes use of data generated by the GCAT=Genomes for Life. Cohort study of the Genomes of Catalonia, Fundacio IGTP with registration number PI-2018–03. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026) and; the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529)

Population genetics of the european Roma-A review

The Roma are a group of populations with a common origin that share the Romani identity and cultural heritage. Their genetic history has been inferred through multiple studies based on uniparental and autosomal markers, and current genomic data have provided novel insights into their genetic background. This review was prompted by two factors: (i) new developments to estimate the genetic structure of the Roma at a fine-scale resolution have precisely identified the ancestral components and traced migrations that were previously documented only in historical sources, clarifying and solving debates on the origins and the diaspora of the Roma; (ii) while there has been an effort to review the health determinants of the Roma, the increasing literature on their population genetics has not been subjected to a dedicated review in the last two decades. We believe that a summary on the state of the art will benefit both the public and scholars that are approaching the subject.This work was supported by the Spanish Ministry of Science, Innovation and Universities (MCIU) and the Agencia Estatal de Investigación (AEI) [PID2019-106485GB-I00/AEI/10.13039/501100011033]; and “Unidad de Excelencia María de Maeztu” [AEI, CEX2018-000792-M]

Admixture has shaped romani genetic diversity in clinically relevant variants

Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; while non-insulin dependent diabetes is enriched in non-Roma Europeans). In addition, previously reported pathogenic variants also show differences among populations, where some variants segregating at low frequency in non-Roma are virtually absent in the Roma. Lastly, we describe frequency changes in drug-response variation, where many of the variants increased in Roma are clinically associated with metabolic and cardiovascular-related drugs. These results suggest that clinically relevant variation in Roma cannot only be characterized in terms of founder mutations. Instead, we observe frequency differences compared to non-Roma: some variants are absent, while other have drifted to higher frequencies. As a result of the admixture events, these clinically damaging variants can be traced back to both European and South Asian-related ancestries. This can be attributed to a different prevalence of some genetic disorders or to the fact that genetic susceptibility variants are mostly studied in populations of European descent, and can differ in individuals with different ancestries

Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation

Human populations are genetically affected by their demographic history, which shapes the distribution of their functional genomic variation. However, the genetic impact of recent demography is debated. This issue has been studied in different populations, but never in North Africans, despite their relevant cultural and demographic diversity. In this study we address the question by analyzing new whole-exome sequences from two culturally different Tunisian populations, an isolated Amazigh population and a close non-isolated Arab-speaking population, focusing on the distribution of functional variation. Both populations present clear differences in their variant frequency distribution, in general and for putatively damaging variation. This suggests a relevant effect in the Amazigh population of genetic isolation, drift, and inbreeding, pointing to relaxed purifying selection. We also discover the enrichment in Imazighen of variation associated to specific diseases or phenotypic traits, but the scarce genetic and biomedical data in the region limits further interpretation. Our results show the genomic impact of recent demography and reveal a clear genetic differentiation probably related to culture. These findings highlight the importance of considering cultural and demographic heterogeneity within North Africa when defining population groups, and the need for more data to improve knowledge on the region's health and disease landscape

The genetic scenario of Mercheros: an under-represented group within the Iberian Peninsula

Background: The general picture of human genetic variation has been vastly depicted in the last years, yet many populations remain broadly understudied. In this work, we analyze for the first time the Merchero population, a Spanish minority ethnic group that has been scarcely studied and historically persecuted. Mercheros have been roughly characterised by an itinerant history, common traditional occupations, and the usage of their own language. Results: Here, we examine the demographic history and genetic scenario of Mercheros, by using genome-wide array data, whole mitochondrial sequences, and Y chromosome STR markers from 25 individuals. These samples have been complemented with a wide-range of present-day populations from Western Eurasia and North Africa. Our results show that the genetic diversity of Mercheros is explained within the context of the Iberian Peninsula, evidencing a modest signal of Roma admixture. In addition, Mercheros present low genetic isolation and intrapopulation heterogeneity. Conclusions: This study represents the first genetic characterisation of the Merchero population, depicting their fine-scale ancestry components and genetic scenario within the Iberian Peninsula. Since ethnicity is not only influenced by genetic ancestry but also cultural factors, other studies from multiple disciplines are needed to further explore the Merchero population. As with Mercheros, there is a considerable gap of underrepresented populations and ethnic groups in publicly available genetic data. Thus, we encourage the consideration of more ethnically diverse population panels in human genetic studies, as an attempt to improve the representation of human populations and better reconstruct their fine-scale history

Genomic insights into the population history of the resande or swedish travelers

The Resande are a minority ethnic group in Sweden, who were characterized by an itinerant way of life, and they have been suggested to originate from the mixture between Swedish and Romani populations. Because the population history of the Resande has been scarcely studied, we analyzed genome-wide genotype array data from unrelated Resande individuals in order to shed light on their origins and demographic history for the first time from a genetic perspective. Our results confirm the Romani-related ancestry of this population and suggest an admixture event between a Romani-like population and a general Swedish-like population that occurred approximately between the mid-18th and mid-19th centuries, two centuries after the arrival of the first historically reported Romani families in Sweden. This inferred date suggests that the Romani group involved in the admixture is related to the pre-18th-century arrivals of Romani in Scandinavia. In addition, a reduction in the population size is detected previous to the admixture event, suggesting a subtle signal of isolation. The present work constitutes a step forward toward a better representation of ethnic minorities and underrepresented groups in population genetic analyses. In order to know in more detail the complete history of human populations, it is time to focus on studying populations that have not been previously considered for a general scenario and that can provide valuable information to fill in the gaps that still remain uncovered.This study was supported by the Ministerio de Ciencia, Innovación y Universidades (MCIU, Spain) and the Agencia Estatal de Investigación (AEI) grant numbers CGL2016-75389-P and PID2019-106485GB481I00/AEI/10.13039/501100011033, and “Unidad de Excelencia María de Maeztu” (MCIN and AEI, DOI:10.13039/501100011033, CEX2018-000792-M)

The genetic landscape of Mediterranean North African populations through complete mtDNA sequences

<p><b>Background:</b> The genetic composition of human North African populations is an amalgam of different ancestral components coming from the Middle East, Europe, south-Saharan Africa and autochthonous to North Africa. This complex genetic pattern is the result of migrations and admixtures in the region since Palaeolithic times.</p> <p><b>Aims:</b> The objective of the present study is to refine knowledge of the population history of North African populations through the analysis of complete mitochondrial sequences.</p> <p><b>Subjects and methods:</b> This study has sequenced complete mitochondrial DNAs (mtDNAs) in several North African and neighbouring individuals.</p> <p><b>Results:</b> The mtDNA haplogroup classification and phylogeny shows a high genetic diversity in the region as a result of continuous admixture. The phylogenetic analysis allowed us to identify a new haplogroup characterised by positions 10 101 C and 146 C (H1v2), a sub-branch of H1v, which is restricted to North Africa and whose origins are estimated as ∼4000 years ago.</p> <p><b>Conclusions:</b> The analysis of the complete mtDNA genome has allowed for the identification of a North African sub-lineage that might be ignored by the analysis of partial mtDNA control region sequences, highlighting the phylogeographic relevance of mtDNA complete sequence analysis.</p