To analyze the contribution of the Czech population to the Y-chromosome diversity landscape of Europe and to reconstruct past demographic events, we typed 257 males from five locations for 21 UEPs. Moreover, 141 carriers of the three most common haplogroups were typed for 10 microsatellites and coalescent analyses applied. Sixteen Hg's characterized by derived alleles were identified, the most common being R1a-SRY(10831) and P-DYS257*(xR1a). The pool of haplogroups within I-M170 represented the third most common clade. Overall, the degree of population structure was low. The ages for Hg I-M170, P-DYS257*(xR1a), and R1a-SRY(10831) ap peared to be comparable and compatible with their presence during or soon after the LGM. A signal of population growth beginning in the first millennium B.C. was detected. Its similarity among the three most common Hg's indicated that growth was characteristic for a gene pool that already contained all of them. The Czech population appears to be influenced, to a very moderate extent, by genetic inputs from outside Europe in the post-Neolithic and historical times. Population growth postdated the archaeologically documented introduction of Neolithic technology and the estimated central value coincides with a period of repeated changes driven by the development of metal technologies and the associated social and trade organization.

• MeSH
• analýza rozptylu MeSH
• DNA primery MeSH
• genetická variace * MeSH
• haplotypy genetika   MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• mikrosatelitní repetice genetika   MeSH
• molekulární evoluce * MeSH
• populační dynamika * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Special conditions are required for genetic differentiation to arise at a local geographical scale in the face of gene flow. The Natal multimammate mouse, Mastomys natalensis, is the most widely distributed and abundant rodent in sub-Saharan Africa. A notorious agricultural pest and a natural host for many zoonotic diseases, it can live in close proximity to humans and appears to compete with other rodents for the synanthropic niche. We surveyed its population genetic structure across a 180-km transect in central Tanzania along which the landscape varied between agricultural land in a rural setting and natural woody vegetation, rivers, roads and a city (Morogoro). We sampled M. natalensis across 10 localities and genotyped 15 microsatellite loci from 515 individuals. Hierarchical STRUCTURE analyses show a K-invariant pattern distinguishing Morogoro suburbs (located in the centre of the transect) from nine surrounding rural localities. Landscape connectivity analyses in Circuitscape and comparison of rainfall patterns suggest that neither geographical isolation nor natural breeding asynchrony could explain the genetic differentiation of the urban population. Using the isolation-with-migration model implemented in IMa2, we inferred that a split between suburban and rural populations would have occurred recently (<150 years ago) with higher urban effective population density consistent with an urban source to rural sink of effective migration. The observed genetic differentiation of urban multimammate mice is striking given the uninterrupted distribution of the animal throughout the landscape and the high estimates of effective migration (2Ne M = 3.0 and 29.7), suggesting a strong selection gradient across the urban boundary.

• MeSH
• migrace zvířat * MeSH
• mikrosatelitní repetice * MeSH
• Murinae genetika   MeSH
• myši MeSH
• populační dynamika MeSH
• tok genů * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Tanzanie MeSH

We used the mitochondrial control region and nuclear microsatellites to assess the distribution patterns, population structure, demography and landscape genetics for the hedgehogs Erinaceus europaeus and Erinaceus roumanicus in a transect of the mid-European zone of sympatry. E. roumanicus was less frequent and restricted to regions with lower altitudes. Demographic analyses suggested recent population growth in this species. A comparison of patterns in the spatial variability of mitochondrial and nuclear DNA indicated less sex-biased dispersal and higher levels of gene flow in E. roumanicus. No evidence of recent hybridisation or introgression was detected. We interpreted these results by comparing with phylogeographic and palaeontological studies as well as with the occurrence of hybridisation in the Russian contact zone. We propose that Central Europe was colonised by E. roumanicus by the beginning of the Neolithic period and that there was a subsequent reinforcement stage as well as the formation of a zone of sympatry after the complete reproductive isolation of both species.

• MeSH
• demografie MeSH
• fylogeografie MeSH
• genetická variace MeSH
• haplotypy MeSH
• ježkovití genetika   MeSH
• mikrosatelitní repetice MeSH
• mitochondriální DNA MeSH
• populační genetika MeSH
• reprodukční izolace MeSH
• sympatrie MeSH
• tok genů MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

The major histocompatibility complex (MHC) genes coding for antigen presenting molecules are the most polymorphic genes in vertebrate genome. The MHC class II DRA gene shows only small variation in many mammalian species, but it exhibits relatively high level of polymorphism in Equidae, especially in donkeys. This extraordinary degree of polymorphism together with signatures of selection in specific amino acids sites makes the donkey DRA gene a suitable model for population diversity studies. The objective of this study was to investigate the DRA gene diversity in three different populations of donkeys under infectious pressure of protozoan parasites, Theileria equi and Babesia caballi. Three populations of domestic donkeys from Italy (N = 68), Jordan (N = 43), and Kenya (N = 78) were studied. A method of the donkey MHC DRA genotyping based on PCR-RFLP and sequencing was designed. In addition to the DRA gene, 12 polymorphic microsatellite loci were genotyped. The presence of Theileria equi and Babesia caballi parasites in peripheral blood was investigated by PCR. Allele and genotype frequencies, observed and expected heterozygosities and F(IS) values were computed as parameters of genetic diversity for all loci genotyped. Genetic distances between the three populations were estimated based on F(ST) values. Statistical associations between parasite infection and genetic polymorphisms were sought. Extensive DRA locus variation characteristic for Equids was found. The results showed differences between populations both in terms of numbers of alleles and their frequencies as well as variation in expected heterozygosity values. Based on comparisons with neutral microsatellite loci, population sub-structure characteristics and association analysis, convincing evidence of pathogen-driven selection at the population level was not provided. It seems that genetic diversity observed in the three populations reflects mostly effects of selective breeding and their different genetic origins.

• MeSH
• babezióza epidemiologie   veterinární   MeSH
• demografie MeSH
• Equidae genetika   metabolismus   MeSH
• genetická variace MeSH
• genotyp MeSH
• geny MHC třídy II genetika   MeSH
• mikrosatelitní repetice MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Afrika MeSH
• Asie MeSH
• Evropa MeSH

Wild boar (Sus scrofa), one of the most widespread wildlife species, has entered a stage of continuous growth in Europe, and could even be considered a pest species. We analysed microsatellite variability in 723 wild boars from across Europe, including the northern Dinaric Balkans. Our aims were: (1) to define the population structure of wild boars in the Balkans and its relation with other European populations; (2) to estimate effective populations sizes, levels of intra- and inter-population diversity, inbreeding migration and gene flow patterns; (3) to test subpopulations for bottlenecks; (4) to interpret these results in light of current knowledge about the demographic history of wild boars in Europe; and (5) to discuss the relevance of these findings for management and conservation. Strong population structuring was observed and 14 subpopulations were revealed. High genetic diversity was found, and besides the well-known identity of the Italian populations of Sardinia and Castelporziano, we bring new insights into other potential relevant, refugial populations such as Littoral Slovenia, South Portugal, North-western Iberia and an entire cluster in the Balkans. There was evidence of gene flow going from these refugial subpopulations towards less peripheral and more admixed subpopulations. Recent population bottlenecks and expansions were detected, mostly in the peninsular refuge subpopulations. The results are consistent with the fluctuations of wild boar numbers in Europe since the beginning of the twentieth century. These results should be taken into account in future conservation and management plans for wild boar populations in Europe.

• MeSH
• frekvence genu MeSH
• genetická variace * MeSH
• genotypizační techniky MeSH
• hustota populace MeSH
• inbreeding MeSH
• mikrosatelitní repetice MeSH
• modely genetické MeSH
• populační dynamika MeSH
• populační genetika * MeSH
• statistické modely MeSH
• Sus scrofa genetika   MeSH
• tok genů * MeSH
• zachování přírodních zdrojů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Balkánský poloostrov MeSH
• Evropa MeSH

South-east Europe, along with the adjacent region of south-west Asia, is an important biodiversity hotspot with high local endemism largely contributed by contemporary continental lineages that retreated to southern refugia during colder Quaternary periods. We investigated the genetic diversity of the European bitterling fish (Rhodeus amarus) species complex (Cyprinidae) across its range in the western Palearctic, but with a particular emphasis in the region of Balkan, Pontic and Caspian refugia. We genotyped 12 polymorphic microsatellite loci and a partial sequence of mitochondrial gene cytochrome b (CYTB) for a set of 1,038 individuals from 60 populations. We used mtDNA sequences to infer phylogenetic relationships and historical demography, and microsatellite markers to describe fine-scale genetic variability and structure. Our mtDNA analysis revealed six well-supported lineages, with limited local co-occurrence. Two lineages are distributed throughout central and western Europe (lineages "A" and "B"), with two zones of secondary contact. Another two lineages were restricted to the Ponto-Aegean region of Greece (lineages "C" and "D") and the final two lineages were restricted south of the Caucasus mountains (lineage "E" from the Black Sea watershed and lineage "F" from the Caspian watershed). A signal of recent expansion was revealed in the two widespread lineages and the Ponto-Aegean lineage "C". The geographic distribution of clusters detected by nuclear microsatellites corresponded well with mitochondrial lineages and demonstrated finely sub-structured populations. A profound population structure suggested a significant role of genetic drift in differentiation among lineages. Lineage divergence in the Ponto-Aegean and Caspian regions are substantial, supporting the validity of two described endemic species (Rhodeus meridionalis as lineage "D" and Rhodeus colchicus as lineage "E") and invite taxonomic evaluation of the other two southern lineages (Thracean "C" and Caspian "F").

• MeSH
• biodiverzita MeSH
• Cyprinidae klasifikace   genetika   MeSH
• cytochromy b genetika   MeSH
• demografie MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genetický drift MeSH
• genotyp MeSH
• mikrosatelitní repetice MeSH
• mitochondriální DNA chemie   MeSH
• mitochondrie genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• západní Asie MeSH

Biological invasions are a global issue with far-reaching consequences for single species, communities and whole ecosystems. Our understanding of modes and mechanisms of biological invasions requires knowledge of the genetic processes associated with successful invasions. In many instances, this information is particularly difficult to obtain as the initial phases of the invasion process often pass unnoticed and we rely on inferences from contemporary population genetic data. Here, we combined historic information with the genetic analysis of resting eggs to reconstruct the invasion of Daphnia pulicaria into Lower Lake Constance (LLC) in the 1970s from the resting egg bank in the sediments. We identified the invader as 'European D. pulicaria' originating from meso- and eutrophic lowland lakes and ponds in Central Europe. The founding population was characterized by extremely low genetic variation in the resting egg bank that increased considerably over time. Furthermore, strong evidence for selfing and/or biparental inbreeding was found during the initial phase of the invasion, followed by a drop of selfing rate to low levels in subsequent decades. Moreover, the increase in genetic variation was most pronounced during early stages of the invasion, suggesting additional introductions during this period. Our study highlights that genetic data covering the entire invasion process from its beginning can be crucial to accurately reconstruct the invasion history of a species. We show that propagule banks can preserve such information enabling the study of population genetic dynamics and sources of genetic variation in successful invasive populations.

• MeSH
• buněčné jádro genetika   MeSH
• Daphnia genetika   MeSH
• frekvence genu MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genetické markery MeSH
• genotyp MeSH
• geologické sedimenty MeSH
• inbreeding MeSH
• jezera MeSH
• mikrosatelitní repetice MeSH
• mitochondriální DNA genetika   MeSH
• modely genetické MeSH
• molekulární sekvence - údaje MeSH
• ovum * MeSH
• populační dynamika MeSH
• populační genetika * MeSH
• sekvenční analýza DNA MeSH
• zavlečené druhy MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Německo MeSH
• Švýcarsko MeSH

Imunoterapie má v léčbě metastazujícího kolorektálního karcinomu své pevné místo u pacientů s mikrosatelitovou instabilitou/ deficiencí v mismatch repair genech tvořících zhruba 5 % všech metastatických kolorektálních karcinomů. Data z menších studií také silně svědčí pro obdobně dobrou účinnost také u tumorů s mutací POLE1/POLD1. Probíhá intenzivní výzkum snažící se prolomit rezistenci k imunoterapii pozorovanou u mikrosatelitně stabilních nádorů kolorekta. Některé menší nerandomizované studie naznačují možný benefit kombinace imunoterapie s multikinázovými inhibitory nebo chemoterapií a cílenou léčbou v populaci mikrosatelitně stabilních tumorů, avšak negativní výsledky několika nedávno publikovaných studií ukazují nutnost dalšího výzkumu před uvedením do praxe. Slibné se jeví testování nové generace imunoterapie.

Immunotherapy has a established role in the treatment of metastatic colorectal cancer in patients with microsatellite instability/deficiency in mismatch repair genes accounting for roughly 5% of all metastatic colorectal cancers. Data from smaller studies also strongly support similarly good efficacy in tumors with the POLE1/POLD1 mutation. Intensive research is underway to break down the resistance to immunotherapy observed in microsatellite stable colorectal cancers. Some smaller non-randomized studies suggest a possible benefit of combining immunotherapy with multikinase inhibitors or chemotherapy and targeted treatment in the population of microsatellite stable tumors, but negative results from several recently published studies indicate the need for further research before implementation into clinical praxis. Promising results were seen with novel generation of immunotherapy agents.

• MeSH
• biologická terapie metody   MeSH
• cílená molekulární terapie metody   MeSH
• imunoterapie metody   MeSH
• klinická studie jako téma MeSH
• kolorektální nádory * diagnóza   farmakoterapie   patologie   MeSH
• lidé MeSH
• mikrosatelitní nestabilita MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

• MeSH
• depresivní poruchy genetika   MeSH
• diabetes mellitus 2. typu genetika   MeSH
• dospělí MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• kardiovaskulární nemoci genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom epidemiologie   genetika   MeSH
• methylentetrahydrofolátreduktasa (NADPH2) genetika   MeSH
• mikrosatelitní repetice MeSH
• mozkový neurotrofický faktor genetika   MeSH
• pilotní projekty MeSH
• polymorfismus genetický MeSH
• rizikové faktory MeSH
• senioři MeSH
• synthasa oxidu dusnatého, typ III genetika   MeSH
• tyrosin-3-monooxygenasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Poznatky o molekulárních subtypech karcinomu endometria vedly v posledních několika letech k velkým změnám v klasifikačních systémech, prognostických skupinách a ve svém důsledku v terapeutických postupech u pacientek s pokročilým/metastazujícím karcinomem endometria. Z pohledu imunoterapeutického lze skupinu karcinomů endometria dělit na mikrosatelitově nestabilní (microsatellite instability-high, MSI-H) a skupinu mikrosatelitově stabilní (microsatellite stability, MSS). Mikrosatelitově nestabilní skupina tumorů zpravidla dobře reaguje na monoterapii checkpoint inhibitory, naopak skupina MSS obvykle vyžaduje k dosažení onkologického úspěchu kombinovanou terapii. Nejvýznamnějším posunem v obtížně léčitelné kohortě pacientek s pokročilým a metastazujícím karcinomem endometria od dob konvenční chemoterapie je jednoznačně kombinace pembrolizumabu s lenvatinibem, nezávislá na přítomnosti MSI-H nádorových buněk. Ve skupině MSI-H karcinomů se jako velmi úspěšná kombinace jeví podání dostarlimabu v monoterapii.

Knowledge of the molecular subtypes of endometrial cancer has led to major changes in classification systems, prognostic groups and, consequently, therapeutic procedures for patients with advanced/metastatic endometrial cancer in the last few years. From the point of view of immunotherapy, the group of endometrial cancers can be divided into microsatellite unstable (microsatellite instability-high, MSI-H) and microsatellite stable (microsatellite stability, MSS). The MSI-H tumor group usually responds well to monotherapy with checkpoint inhibitors, whereas the MSS group usually requires combined therapy to achieve oncological success. The most significant shift in the difficult-to-treat cohort of patients with advanced and metastatic endometrial cancer since the days of conventional chemotherapy is clearly the combination of pembrolizumab with lenvatinib, independent of the presence of microsatellite instability of tumor cells. In the group of MSI-H carcinomas, the administration of dostarlimab in monotherapy appears to be a very successful combination.

• Klíčová slova
• dMMR/MSI-H karcinom,
• MeSH
• děložní krvácení MeSH
• imunoterapie * MeSH
• inhibitory kontrolních bodů MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• nádory endometria * chirurgie   diagnóza   epidemiologie   klasifikace   MeSH
• postmenopauza MeSH
• protinádorové látky MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH