Dear Colleagues,

Despite the large amount of shared variants between modern humans due to their recent African origin ~300,000 years ago, specific genetic diversity is accumulating in the various human populations. The structure between the main human population groups was generated by the out-of-Africa migration ~70,000 years ago, when a small group of eastern Africans gave rise to all European and Asian (and, consequently, Native American) populations. Most human genome variants are neutral, changing randomly in frequency along generations, but a clinically important fraction is under the influence of selection. In humans, negative selection is the most common type of selection, leading to a decrease in the frequency of deleterious variants. However, a few deleterious variants can be preserved in populations by balancing selection, due to heterozygote advantage or frequency-dependent selection. Recent genomic screenings are identifying an increasing number of positively selected variants whose frequency is driven by environmental adaptations, such as exposure to pathogens and changes in lifestyle. Interestingly, selection can also occur through population admixture, in which the admixed group shows enrichment on a specific ancestry in regions of the genome where advantageous variants are located. This type of selection is called adaptive introgression or adaptive admixture, depending on the founder being an archaic or modern human population, respectively.

The omics revolution is paramount to allowing unbiased holistic evaluation, big data generation, and clearer genome–phenome relation. Various omics levels are currently available: genomics, exomics, transcriptomics, proteomics, methylomics, immunomics, lipidomics, metabolomics, microbiomics, and pharmacogenomics. These omics bring several challenges, as more careful sample collection (e.g., involving freezing preservation), higher financial investment, and multi-technical competences, rendering its application in middle- and low-income populations difficult. Indeed, the bias for European descendants in genome-wide association catalogues and in available non-diseased and diseased exome and genome databases is overwhelming. This delays attaining saturation on new variants identified in the human species. Furthermore, better global allele frequency characterization provides insightful information for updating the status classification of variants as neutral or of clinical interest. Identified adaptations in specific population groups can elucidate the best molecular mechanisms for pharmacological intervention, aiming to improve global human well-being. The poor multi-ethnicity background also affects available in vitro models, such as cancer cell lines and induced pluripotent stem cells, significantly impairing a proper functional evaluation of the ancestry impact on the phenome.

This Special Issue is open to reviews and original contributions on the following topics: (1) omics characterization of non-diseased and diseased multi-ethnic populations, (2) evaluation of selection along time and space, (3) functional modelling with ancestry-informative tools, (4) molecular-based epidemiology of diseases/complex phenotypes with frequency disparities between population groups, and (5) ethical considerations and designing of inclusive precision medicine approaches.

Prof. Dr. Luisa Pereira
Dr. Verónica Fernandes
Guest Editors

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• omics diversity
• ancestry and multi-ethnic representation
• health and disease
• selection and adaptation
• genome-phenome binomial
• functional evaluations accounting for ancestry
• ethical considerations
• inclusive precision medicine