Twenty-seven ZAD-ZNF genes of Drosophila melanogaster are orthologous to the embryo polarity determining mosquito gene cucoid.

The C2H2 zinc finger gene cucoid establishes anterior-posterior (AP) polarity in the early embryo of culicine mosquitoes. This gene is unrelated to genes that establish embryo polarity in other fly species (Diptera), such as the homeobox gene bicoid, which serves this function in the traditional model organism Drosophila melanogaster. The cucoid gene is a conserved single copy gene across lower dipterans but nothing is known about its function in other species, and its evolution in higher dipterans, including Drosophila, is unresolved. We found that cucoid is a member of the ZAD-containing C2H2 zinc finger (ZAD-ZNF) gene family and is orthologous to 27 of the 91 members of this family in D. melanogaster, including M1BP, ranshi, ouib, nom, zaf1, odj, Nnk, trem, Zif, and eighteen uncharacterized genes. Available knowledge of the functions of cucoid orthologs in Drosophila melanogaster suggest that the progenitor of this lineage specific expansion may have played a role in regulating chromatin. We also describe many aspects of the gene duplication history of cucoid in the brachyceran lineage of D. melanogaster, thereby providing a framework for predicting potential redundancies among these genes in D. melanogaster.

Using phylogeographic link-prediction in primates to prioritize human parasite screening.

Objectives: The ongoing risk of emerging infectious disease has renewed calls for understanding the origins of zoonoses and identifying future zoonotic disease threats. Given their close phylogenetic relatedness and geographic overlap with humans, non-human primates (NHPs) have been the source of many infectious diseases throughout human evolution. NHPs harbor diverse parasites, with some infecting only a single host species while others infect species from multiple families. Materials and Methods: We applied a novel link-prediction method to predict undocumented instances of parasite sharing between humans and NHPs. Our model makes predictions based on phylogenetic distances and geographic overlap among NHPs and humans in six countries with high NHP diversity: Columbia, Brazil, Democratic Republic of Congo, Madagascar, China and Indonesia. Results: Of the 899 human parasites documented in the Global Infectious Diseases and Epidemiology Network (GIDEON) database for these countries, 12% were shared with at least one other NHP species. The link prediction model identified an additional 54 parasites that are likely to infect humans but were not reported in GIDEON. These parasites were mostly host generalists, yet their phylogenetic host breadth varied substantially. Discussion: As human activities and populations encroach on NHP habitats, opportunities for parasite sharing between human and non-human primates will continue to increase. Our study identifies specific infectious organisms to monitor in countries with high NHP diversity, while the comparative analysis of host generalism, parasite taxonomy, and transmission mode provides insights to types of parasites that represent high zoonotic risk.

Gene Hunting Approaches through the Combination of Linkage Analysis with Whole-Exome Sequencing in Mendelian Diseases: From Darwin to the Present Day.

BACKGROUND: In the context of medical genetics, gene hunting is the process of identifying and functionally characterizing genes or genetic variations that contribute to disease phenotypes. In this review, we would like to summarize gene hunting process in terms of historical aspects from Darwin to now. For this purpose, different approaches and recent developments will be detailed. SUMMARY: Linkage analysis and association studies are the most common methods in use for explaining the genetic background of hereditary diseases and disorders. Although linkage analysis is a relatively old approach, it is still a powerful method to detect disease-causing rare variants using family-based data, particularly for consanguineous marriages. As is known that, consanguineous marriages or endogamy poses a social problem in developing countries, however, this same condition also provides a unique opportunity for scientists to identify and characterize pathogenic variants. The rapid advancements in sequencing technologies and their parallel implementation together with linkage analyses now allow us to identify the candidate variants related to diseases in a relatively short time. Furthermore, we can now go one step further and functionally characterize the causative variant through in vitro and in vivo studies and unveil the variant-phenotype relationships on a molecular level more robustly. Key Messages: Herein, we suggest that the combined analysis of linkage and exome analysis is a powerful and precise tool to diagnose clinically rare and recessively inherited conditions.