The Roma Diaspora — traditionally known as Gypsies —remains amongst the least explored population migratory events in historical times. It involved the migration of Roma ancestors out-of-India through the plateaus of Western Asia ultimately reaching Europe. The demographic effects of the Diaspora – bottlenecks, endogamy, and gene flow – might have left marked molecular traces in the Roma genomes. Here, we analyze the whole genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. Our analyses revealed a strong, early founder effect followed by a drastic reduction of ∼44% in effective population size. The Roma common ancestors split from the Punjabi population, from -Northwest India, some generations before the Diaspora started, less than 2,000 years ago. The initial bottleneck and subsequent endogamy are revealed by the occurrence of extensive Runs of Homozygosity and Identity By Descendent segments in all Roma populations. Furthermore, we provide evidence of gene flow from Armenian and Anatolian groups in present-day Roma, although the primary contribution to Roma gene pool comes from non-Roma Europeans, which accounts for more than 50% of their genomes. The linguistic and historical differentiation of Roma in migrant groups is confirmed by the differential proportion, but not a differential source, of European admixture in the Roma groups, which shows a westward cline. In the present study we found that despite the strong admixture Roma had in their diaspora, the signature of the initial bottleneck and the subsequent endogamy is still present in Roma genomes.
Fragile X syndrome (FXS) is the most frequent monogenic cause of autism or intellectual disability, and research on its pathogenetic mechanisms has provided important insights on this neurodevelopmental condition. Nevertheless, after 30 years of intense research, efforts to develop treatments have been mostly unsuccessful. The aim of this review is to compile evidence from existing research pointing to clinical, genetic, and therapeutic response heterogeneity in FXS and highlight the need of implementing precision medicine-based treatments. We comment on the high genetic and phenotypic heterogeneity present in FXS, as a contributing factor to the difficulties found during drug development. Given that several clinical trials have showed a non-negligeable fraction of positive responders to drugs targeting core FXS symptoms, we propose that success of clinical trials can be achieved by tackling the underlying heterogeneity in FXS by accurately stratifying patients into drug-responder subpopulations. These precision medicine-based approaches, which can be first applied to well-defined monogenic diseases such as FXS, can also serve to define drug responder profiles based on specific biomarkers or phenotypic features that can associate patients with different genetic backgrounds to a same candidate drug, thus repositioning a same drug for a larger number of patients with NDDs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.