Active spread of ß-thalassemia beyond the thalassemia belt: A study on a Russian population.

ß-Thalassemia is a disease traditionally associated with thalassemia belt countries. Nonetheless, as global migration intensifies, ß-thalassemia-causing variants spread far from their origin. We investigated this process to detect some patterns underlying its course. We analyzed ß-thalassemia-causing variants and the origin of 676 unrelated participants in Moscow, the largest city of Russia, far away from the thalassemia belt. Our analyses revealed that modern Russia has one of the broadest spectra of thalassemia-causing variants: 46 different variants, including two novel ß0 variants. Only a small proportion of the reported pathogenic variants likely originated in the resident subpopulation. Almost half of the variants that supposedly had emerged outside the Russian borders have already been assimilated by (were found in) the resident subpopulation. The primary modern source of immigration transferring thalassemia to a nonthalassemic part of Russia is the Caucasus region. We also found traces of ancient migration flows from non-Caucasus countries. Our data indicate that ß-thalassemia-causing variants are actively spilling over into resident populations of countries outside thalassemia belt regions. Therefore, viewing thalassemia as a disease exclusive to specific ethnic groups creates a mind trap that can complicate the diagnosis.

Traditional multilocus phylogeny fails to fully resolve Palearctic ground squirrels (Spermophilus) relationships but reveals a new species endemic to West Siberia.

Previous efforts to reconstruct evolutionary history of Palearctic ground squirrels within the genus Spermophilus have primarily relied on a single mitochondrial marker for phylogenetic data. In this study, we present the first phylogeny with comprehensive taxon sampling of Spermophilus via a conventional multilocus approach utilizing five mitochondrial and five nuclear markers. Through application of the multispecies coalescent model, we constructed a species tree revealing four distinct clades that diverged during the Late Miocene. These clades are 1) S. alaschanicus and S. dauricus from East Asia; 2) S. musicus and S. pygmaeus from East Europe and northwestern Central Asia; 3) the subgenus Colobotis found across Central Asia and its adjacent regions and encompassing S. brevicauda, S. erythrogenys, S. fulvus, S. major, S. pallidicauda, S. ralli, S. relictus, S. selevini, and S. vorontsovi sp. nov.; and 4) a Central/Eastern Europe and Asia Minor clade comprising S. citellus, S. taurensis, S. xanthoprymnus, S. suslicus, and S. odessanus. The latter clade lacked strong support owing to uncertainty of taxonomic placement of S. odessanus and S. suslicus. Resolving relationships within the subgenus Colobotis, which radiated rapidly, remains challenging likely because of incomplete lineage sorting and introgressive hybridization. Most of modern Spermophilus species diversified during the Early-Middle Pleistocene (2.2-1.0 million years ago). We propose a revised taxonomic classification for the genus Spermophilus by recognizing 18 species including a newly identified one (S. vorontsovi sp. nov.), which is found only in a limited area in the southeast of West Siberia. Employing genome-wide single-nucleotide polymorphism genotyping, we substantiated the role of the Ob River as a major barrier ensuring robust isolation of this taxon from S. erythrogenys. Despite its inherent limitations, the traditional multilocus approach remains a valuable tool for resolving relationships and can provide important insights into otherwise poorly understood groups. It is imperative to recognize that additional efforts are needed to definitively determine phylogenetic relationships between certain species of Palearctic ground squirrels.

A founder effect in hemophilia A patients from Russian Ural region with a new p.(His634Arg) variant in F8 gene.

Hemophilia A is a clotting disease caused by defects in the F8 gene. A lot of them are described and most are unique or have polyphyletic origin. We here study the origin of a pathogenic variant found in a few patients. We sequenced F8 gene for seven hemophilia A patients from the Ural region, Sverdlovskaya oblast, Russia. We constructed haplotypes for them and for 21 hemophilia A patients with other defects from the same area as a control group using four previously described X-chromosome loci associated with F8 gene. We identified a new missense variant p.(His634Arg) in seven apparently unrelated patients with mild hemophilia A from Sverdlovskaya oblast. The haplotype analysis showed that all patients share the same haplotype, absent in the other patients, suggesting a founder effect. The most recent common ancestor for the p.(His634Arg) patients is estimated to exist around the end of XVII century; however, the 95% confidence interval spans from XII to early XX century. The Ural region did not suffer from the recent bottlenecks or isolation. Therefore, the founder effect could be a natural consequence of population structuring in a relatively stable population. We identified a founder effect mutation in hemophilia A, which is a quite rare event for this disease.

DNA analysis of a 30,000-year-old Urocitellus glacialis from northeastern Siberia reveals phylogenetic relationships between ancient and present-day arctic ground squirrels.

In contrast to the abundant fossil record of arctic ground squirrels, Urocitellus parryii, from eastern Beringia, only a limited number of fossils is known from its western part. In 1946, unnamed GULAG prisoners discovered a nest with three mummified carcasses of arctic ground squirrels in the permafrost sediments of the El'ga river, Yakutia, Russia, that were later attributed to a new species, Citellus (Urocitellus) glacialis Vinogr. To verify this assignment and to explore phylogenetic relationships between ancient and present-day arctic ground squirrels, we performed 14C dating and ancient DNA analyses of one of the El'ga mummies and four contemporaneous fossils from Duvanny Yar, northeastern Yakutia. Phylogenetic reconstructions, based on complete cytochrome b gene sequences of five Late Pleistocene arctic ground squirrels and those of modern U. parryii from 21 locations across western Beringia, provided no support for earlier proposals that ancient arctic ground squirrels from Siberia constitute a distinct species. In fact, we observed genetic continuity of the glacialis mitochondrial DNA lineage in modern U. parryii of the Kamchatka peninsula. When viewed in a broader geographic perspective, our findings provide new insights into the genetic history of U. parryii in Late Pleistocene Beringia.

Implications of hybridization, NUMTs, and overlooked diversity for DNA Barcoding of Eurasian ground squirrels.

The utility of DNA Barcoding for species identification and discovery has catalyzed a concerted effort to build the global reference library; however, many animal groups of economical or conservational importance remain poorly represented. This study aims to contribute DNA barcode records for all ground squirrel species (Xerinae, Sciuridae, Rodentia) inhabiting Eurasia and to test efficiency of this approach for species discrimination. Cytochrome c oxidase subunit 1 (COI) gene sequences were obtained for 97 individuals representing 16 ground squirrel species of which 12 were correctly identified. Taxonomic allocation of some specimens within four species was complicated by geographically restricted mtDNA introgression. Exclusion of individuals with introgressed mtDNA allowed reaching a 91.6% identification success rate. Significant COI divergence (3.5-4.4%) was observed within the most widespread ground squirrel species (Spermophilus erythrogenys, S. pygmaeus, S. suslicus, Urocitellus undulatus), suggesting the presence of cryptic species. A single putative NUMT (nuclear mitochondrial pseudogene) sequence was recovered during molecular analysis; mitochondrial COI from this sample was amplified following re-extraction of DNA. Our data show high discrimination ability of 100 bp COI fragments for Eurasian ground squirrels (84.3%) with no incorrect assessments, underscoring the potential utility of the existing reference librariy for the development of diagnostic 'mini-barcodes'.