Discovery of novel genetic syndromes in Latin America: Opportunities and challenges

Abstract

Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA.

Figure 1 -. Correlation between estimated population of Latin American countries and their mentions in OMIM entries. The population estimations were obtained from wikipedia.org, which in turn obtained those numbers from international or national official organisations, whereas the OMIM entries were searched using the terms “country name” OR “its demonym” (e.g. Argentina OR Argentinian). The results were retrieved from both sources on 9th June 2023.

Figure 2 -. Steps currently performed for the discovery of novel gene-disease associations. The workflow of discovery of novel genetic syndromes is summarised in 9 basic and critical steps, from the evaluation of an index patient to the confirmation of the novel condition over time, considering how this type of research is performed nowadays with current techniques. 1) Clinical evaluation and requisition of genomic test, 2) return of negative results in already-associated genes, 3) analysis of raw data focused on unreported genes/variants, 4) identification of candidate variant(s)/gene according to metrics, 5) checking of previous findings using ClinGen criteria, 6) submission of clinical and genetic data to repositories, 7) comparison of clinical data amongst patients and development of functional studies, 8) publication of NGDA, and 9) expansion of evidence with further cohorts and functional data. Created with BioRender.com.

Figure 3 -. Opportunities and challenges that LatAm has to contribute to the discovery of NGDA. The opportunities (denoted with a green tick) and challenges (denoted with a red cross) of the continent are summarised in the same steps described for the discovery of NGDA workflow. Abbreviations and symbols: BI=Bioinformatics/Bioinformatician, #=Number, ↑=Increase. Created with BioRender.com.