Endogénne retrovírusy (ERV) sú genetické elementy, ktoré boli integrované do genómu hostiteľa pred viac ako 100 miliónmi rokov. Ich integrácia prebehla v zárodočných bunkách, čím sa v ľudskej populácii zabezpečil ich prenos z generácie na generáciu. V súčasnosti sa predpokladá, že tvoria až 8 % ľudského genómu. V priebehu evolúcie došlo v endogénnych retrovírusoch ku hromadeniu rôznych mutácii, čo viedlo k ich znefunkčneniu, a preto sa v minulosti považovali za odpadovú DNA. V posledných rokoch sa však ukazuje, že nie sú úplne nefunkčné. S pribúdajúcimi analýzami ľudského genómu sa odhaľujú ich potenciálne úlohy aj v ľudskom organizme.
Endogenous retroviruses (ERVs) are genetic elements that were integrated into the host genome more than 100 million years ago. Their integration took place in germ cells, ensuring their vertical transmission in the human population. They are currently thought to make up to 8 % of the human genome. During evolution, various mutations have accumulated in endogenous retroviruses, leading to their dysfunction, and were therefore considered as junk DNA in the past. However, in recent years it has turned out that they are not completely dysfunctional. With more data becoming available from human genome analyses, their potential roles in the human body are being revealed.
- MeSH
- autoimunitní nemoci etiologie virologie MeSH
- endogenní retroviry * genetika metabolismus MeSH
- genom lidský genetika MeSH
- genom virový genetika MeSH
- integrace viru genetika MeSH
- lidé MeSH
- Retroviridae - proteiny onkogenní genetika metabolismus MeSH
- Retroviridae genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antropologie metody MeSH
- databáze nukleových kyselin MeSH
- genom lidský genetika MeSH
- lidé MeSH
- metadata MeSH
- mitochondriální DNA analýza genetika MeSH
- starobylá DNA * analýza izolace a purifikace MeSH
- vývoj člověka MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antropologie metody MeSH
- genom lidský genetika MeSH
- lidé MeSH
- neandertálci genetika MeSH
- populační genetika MeSH
- starobylá DNA * analýza izolace a purifikace MeSH
- tok genů genetika MeSH
- vývoj člověka MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The demographic history of East-Central Europe after the Neolithic period remains poorly explored, despite this region being on the confluence of various ecological zones and cultural entities. Here, the descendants of societies associated with steppe pastoralists form Early Bronze Age were followed by Middle Bronze Age populations displaying unique characteristics. Particularly, the predominance of collective burials, the scale of which, was previously seen only in the Neolithic. The extent to which this re-emergence of older traditions is a result of genetic shift or social changes in the MBA is a subject of debate. Here by analysing 91 newly generated genomes from Bronze Age individuals from present Poland and Ukraine, we discovered that Middle Bronze Age populations were formed by an additional admixture event involving a population with relatively high proportions of genetic component associated with European hunter-gatherers and that their social structure was based on, primarily patrilocal, multigenerational kin-groups.
- MeSH
- dějiny starověku MeSH
- genom lidský * genetika MeSH
- lidé MeSH
- migrace lidstva * MeSH
- sociální změna MeSH
- Check Tag
- dějiny starověku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Polsko MeSH
PURPOSE: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. METHODS: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. RESULTS: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. CONCLUSION: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH.
- MeSH
- genetická variace genetika MeSH
- genetické testování metody MeSH
- genom lidský * genetika MeSH
- genomika metody MeSH
- hyperlipoproteinemie typ II * genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Stárnutí je proces postupného snižování schopností a funkčních kapacit organismu. Jedná se o univerzální děj se značným stupněm variability, který je charakteristický pro všechny vyšší živočichy. Mezi teoriemi popisujícími stárnutí dominuje v současné době teorie akumulace poškození, která integruje dosud známé mechanismy stárnutí. Teorie se opírá o skutečnost, že při patofyziologických procesech může v lidském těle docházet k nežádoucím změnám, které lze chápat jako poškození. Vlivem průběžné akumulace těchto poškození dochází následně k deterioraci celého systému. Uvádíme základní patofyziologické mechanismy stárnutí (poškození) s ohledem na nejnovější vědecké poznatky a ukazujeme jejich hierarchické souvislosti.
Aging is a process of gradually reducing abilities and functional capacities of the organism. It is a universal process with a considerable degree of variability that is characteristic of all higher animals. Among the theories of ageing, the theory of damage accumulation, which integrates the mechanisms of ageing known to date, is currently widely accepted. This theory is based on pathophysiological processes, injurious changes can occur in the human body. These changes can be understood as damage. Due to the continuous accumulation of damage, the whole system is subsequently deteriorated. The aim of the present work is to characterize the basic pathophysiological mechanisms of aging (damage) in the light of current scientific knowledge and to show them in their hierarchical context.
- MeSH
- genom lidský fyziologie genetika MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí buněk fyziologie genetika MeSH
- stárnutí * fyziologie genetika patologie MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- přehledy MeSH
Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
- MeSH
- Asijci genetika MeSH
- Bayesova věta MeSH
- celogenomová asociační studie MeSH
- genetická predispozice k nemoci * MeSH
- genom lidský genetika MeSH
- hodnocení rizik * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kolorektální nádory epidemiologie genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multifaktoriální dědičnost genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
DNA is a fundamentally important molecule for all cellular organisms due to its biological role as the store of hereditary, genetic information. On the one hand, genomic DNA is very stable, both in chemical and biological contexts, and this assists its genetic functions. On the other hand, it is also a dynamic molecule, and constant changes in its structure and sequence drive many biological processes, including adaptation and evolution of organisms. DNA genomes contain significant amounts of repetitive sequences, which have divergent functions in the complex processes that involve DNA, including replication, recombination, repair, and transcription. Through their involvement in these processes, repetitive DNA sequences influence the genetic instability and evolution of DNA molecules and they are located non-randomly in all genomes. Mechanisms that influence such genetic instability have been studied in many organisms, including within human genomes where they are linked to various human diseases. Here, we review our understanding of short, simple DNA repeats across a diverse range of bacteria, comparing the prevalence of repetitive DNA sequences in different genomes. We describe the range of DNA structures that have been observed in such repeats, focusing on their propensity to form local, non-B-DNA structures. Finally, we discuss the biological significance of such unusual DNA structures and relate this to studies where the impacts of DNA metabolism on genetic stability are linked to human diseases. Overall, we show that simple DNA repeats in bacteria serve as excellent and tractable experimental models for biochemical studies of their cellular functions and influences.
- MeSH
- Bacteria genetika MeSH
- DNA genetika ultrastruktura MeSH
- genom bakteriální genetika MeSH
- genom lidský genetika MeSH
- konformace nukleové kyseliny MeSH
- lidé MeSH
- mikrosatelitní repetice genetika MeSH
- nestabilita genomu genetika MeSH
- repetitivní sekvence nukleových kyselin genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
