1st ed. xii, 346 s.
- Conspectus
- Obecná genetika. Obecná cytogenetika. Evoluce
- NML Fields
- biologie
- genetika, lékařská genetika
Databáze MIM vznikala postupně v 60. letech minulého století a její internetová podoba je k dispozici od roku 1985. V roce 1998 vyšlo poslední tištěné vydání o třech svazcích. Původní náplní databáze byly informace o jednoduše dědičných poruchách, která však díky rozvoji poznání lidského genomu rozšířila svůj obsah na celý jaderný i mimojaderný genom a zařadila i chorobné stavy se složitou dědičností a epigenetické zásahy do funkce lidského genomu. Stala se nepostradatelnou pomůckou pro genetiky a stává se stále užitečnější i pro ostatní medicínské obory. Obdiv k této zřejmě nejvíce oceňované aktivitě prof.V. A. McKusicka by ovšem neměl zastínit i jeho ostatní aktivity, například jeho podíl na Evropské škole lékařské genetiky, kterou již dvacet let v několika specializovaných bězích ročně pořádá v Itálii prof. Giovanni Romeo (se stručnou biografií prof. V. A. Kusicka).
McKusick's database MIM has grown since its early beginning in sixties to 1985 when the online version (OMIM) appeared. The last edition of three volumes was printed in 1998. It has become a very valuable tool for all geneticists, and also clinicians of other disciplines started using it as a source of important information. The original limitation to disorders with mendelian inheritance has been step by step broken down, all components of human genome and also genes without known function and their epigenetic changes have been included. It was a pleasure for all of us to congratulate to McKusick's honorary degree obtained this year by the oldest European university in Bologna (with a short biography).
Epigenetické regulace jsou definovány jako dědičné změny na úrovni genové exprese, které nastávají bez úpravy DNA sekvence. Mezi nej- podstatnější epigenetické mechanismy u člověka patří DNA metylace, kovalentní histonové modifikace a RNA interference. Závěry z mnoha epidemiologických a experimentálních studií naznačují, že riziko vzniku alergií a astmatu je zčásti determinováno environmentálními faktory, jež indukují epigenetické změny. Epigenetické mechanismy se uplatňují již v raném embryonálním vývoji, a proto je nutné zahájit prevenci alergie v prenatálním období. Výsledný fenotypový projev závisí na interakci genetické výbavy jedince s vnějším prostředím.
Epigenetic regulation is defined as inheritable changes in gene expression, without alternation in the DNA sequence. The most e ssential epige- netic mechanisms in mammals comprise DNA methylation, covalent histone modifications and RNA interference. Data from epidemiolo gic and experimental studies indicate that the risk of allergy and asthma may be determined by environmental factors inducing some epig enetic changes. Epigenetic mechanisms are pronounced in the embryonal development. Therefore, it is necessary to start with intervention to pre vent allergy even in the prenatal period or in the early postnatal life. Final phenotype is the result of countless interactions between gen es and environment.
- Keywords
- astma, epigenetika,
- MeSH
- Hypersensitivity etiology genetics MeSH
- Epigenesis, Genetic genetics immunology MeSH
- Financing, Organized MeSH
- Humans MeSH
- DNA Methylation genetics immunology MeSH
- Methylation MeSH
- Environmental Illness prevention & control MeSH
- Gene Silencing physiology immunology MeSH
- Environmental Exposure MeSH
- Prenatal Exposure Delayed Effects prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Chromatin is assembled by histone chaperones such as chromatin assembly factor CAF-1. We had noticed that vigor of Arabidopsis thaliana CAF-1 mutants decreased over several generations. Because changes in mutant phenotype severity over generations are unusual, we asked how repeated selfing of Arabidopsis CAF-1 mutants affects phenotype severity. CAF-1 mutant plants of various generations were grown, and developmental phenotypes, transcriptomes and DNA cytosine-methylation profiles were compared quantitatively. Shoot- and root-related growth phenotypes were progressively more affected in successive generations of CAF-1 mutants. Early and late generations of the fasciata (fas)2-4 CAF-1 mutant displayed only limited changes in gene expression, of which increasing upregulation of plant defense-related genes reflects the transgenerational phenotype aggravation. Likewise, global DNA methylation in the sequence context CHG but not CG or CHH (where H = A, T or C) changed over generations in fas2-4. Crossing early and late generation fas2-4 plants established that the maternal contribution to the phenotype severity exceeds the paternal contribution. Together, epigenetic rather than genetic mechanisms underlie the progressive developmental phenotype aggravation in the Arabidopsis CAF-1 mutants and preferred maternal transmission reveals a more efficient reprogramming of epigenetic information in the male than the female germline.
- MeSH
- Alleles MeSH
- Arabidopsis genetics MeSH
- Epigenesis, Genetic * MeSH
- Phenotype MeSH
- Stress, Physiological genetics MeSH
- Gene Ontology MeSH
- DNA Methylation genetics MeSH
- Mutation genetics MeSH
- Plant Infertility MeSH
- Arabidopsis Proteins genetics metabolism MeSH
- Gene Expression Regulation, Plant MeSH
- Base Sequence MeSH
- Seeds embryology MeSH
- RNA Splicing Factors genetics metabolism MeSH
- Transcriptome genetics MeSH
- Inheritance Patterns genetics MeSH
- Ovule embryology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Male infertility is a worldwide problem associated with genetic background, environmental factors, and diseases. One of the suspected contributing factors to male infertility is diabetes mellitus. We investigated the molecular and morphological changes in sperms and testicular tissue of diabetic males. The study was performed in streptozotocin-induced type 1 diabetes mouse model. Diabetes decreased sperm concentration and viability and increased sperm apoptosis. Changes in protamine 1/protamine 2 ratio indicated reduced sperm quality. The testicular tissue of diabetic males showed significant tissue damage, disruption of meiotic progression, and changes in the expression of genes encoding proteins important for spermiogenesis. Paternal diabetes altered sperm quality and expression pattern in the testes in offspring of two subsequent generations. Our study revealed that paternal diabetes increased susceptibility to infertility in offspring through gametic alternations. Our data also provide a mechanistic basis for transgenerational inheritance of diabetes-associated pathologies since protamines may be involved in epigenetic regulations.
- MeSH
- Biomarkers MeSH
- Diabetes Mellitus, Type 1 complications metabolism MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease * MeSH
- Meiosis MeSH
- Infertility, Male etiology MeSH
- Mice MeSH
- Protamines metabolism MeSH
- Spermatogenesis MeSH
- Spermatozoa metabolism MeSH
- Testis metabolism MeSH
- Inheritance Patterns * MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges.
- Publication type
- Journal Article MeSH
- Review MeSH
The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental factors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factors but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics.
- MeSH
- Epigenesis, Genetic genetics MeSH
- Humans MeSH
- Metabolic Syndrome genetics metabolism MeSH
- Disease Susceptibility metabolism MeSH
- Inheritance Patterns genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Epigenetic variation has been proposed to contribute to the success of asexual plants, either as a contributor to phenotypic plasticity or by enabling transient adaptation via selection on transgenerationally stable, but reversible, epialleles. While recent studies in experimental plant populations have shown the potential for epigenetic mechanisms to contribute to adaptive phenotypes, it remains unknown whether heritable variation in ecologically relevant traits is at least partially epigenetically determined in natural populations. Here, we tested the hypothesis that DNA methylation variation contributes to heritable differences in flowering time within a single widespread apomictic clonal lineage of the common dandelion (Taraxacum officinale s. lat.). Apomictic clone members of the same apomictic lineage collected from different field sites showed heritable differences in flowering time, which was correlated with inherited differences in methylation-sensitive AFLP marker profiles. Differences in flowering between apomictic clone members were significantly reduced after in vivo demethylation using the DNA methyltransferase inhibitor zebularine. This synchronization of flowering times suggests that flowering time divergence within an apomictic lineage was mediated by differences in DNA methylation. While the underlying basis of the methylation polymorphism at functional flowering time-affecting loci remains to be demonstrated, our study shows that epigenetic variation contributes to heritable phenotypic divergence in ecologically relevant traits in natural plant populations. This result also suggests that epigenetic mechanisms can facilitate adaptive divergence within genetically uniform asexual lineages.
- MeSH
- Amplified Fragment Length Polymorphism Analysis MeSH
- Epigenesis, Genetic * MeSH
- Flowers physiology MeSH
- DNA Methylation * MeSH
- Microsatellite Repeats MeSH
- Reproduction, Asexual MeSH
- Genetics, Population MeSH
- Taraxacum genetics physiology MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Finland MeSH
- Germany MeSH
Uniparental silencing of 35S rRNA genes (rDNA), known as nucleolar dominance (ND), is common in interspecific hybrids. Allotetraploid Tragopogon mirus composed of Tragopogon dubius (d) and Tragopogon porrifolius (p) genomes shows highly variable ND. To examine the molecular basis of such variation, we studied the genetic and epigenetic features of rDNA homeologs in several lines derived from recently and independently formed natural populations. Inbred lines derived from T. mirus with a dominant d-rDNA homeolog transmitted this expression pattern over generations, which may explain why it is prevalent among natural populations. In contrast, lines derived from the p-rDNA dominant progenitor were meiotically unstable, frequently switching to co-dominance. Interpopulation crosses between progenitors displaying reciprocal ND resulted in d-rDNA dominance, indicating immediate suppression of p-homeologs in F1 hybrids. Original p-rDNA dominance was not restored in later generations, even in those segregants that inherited the corresponding parental rDNA genotype, thus indicating the generation of additional p-rDNA and d-rDNA epigenetic variants. Despite preserved intergenic spacer (IGS) structure, they showed altered cytosine methylation and chromatin condensation patterns, and a correlation between expression, hypomethylation of RNA Pol I promoters and chromatin decondensation was apparent. Reversion of such epigenetic variants occurred rarely, resulting in co-dominance maintained in individuals with distinct genotypes. Generally, interpopulation crosses may generate epialleles that are not present in natural populations, underlying epigenetic dynamics in young allopolyploids. We hypothesize that highly expressed variants with distinct IGS features may induce heritable epigenetic reprogramming of the partner rDNA arrays, harmonizing the expression of thousands of genes in allopolyploids.
- MeSH
- DNA, Plant genetics MeSH
- Epigenomics * MeSH
- Phenotype MeSH
- Genome, Plant genetics MeSH
- Genotype MeSH
- Hybridization, Genetic MeSH
- DNA Methylation MeSH
- Evolution, Molecular * MeSH
- Polyploidy MeSH
- Gene Expression Regulation, Plant * MeSH
- DNA, Ribosomal genetics MeSH
- Tragopogon genetics MeSH
- Gene Silencing MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Fenotyp člověka je ovládán genotypem – souborem genetických informací uložených v DNA. Pokud si pomůžeme s tradiční terminologií, jde o něco přes 20 000 genů, jejichž vliv na utváření fenotypu je různě „silný“ a uplatňuje se většinou v rámci celého genomu, tedy v prostředí plném působení ostatních genů. Výsledný efekt je závislý nejen na pevně stanovených programech, které jsme zdědili od svých předků (a jejichž minulost bychom mohli sledovat do samého počátku života na zemi, který začal používat informační molekuly nukleových kyselin), ale i na vnějších vlivech, které na organismus působily od okamžiku jeho vzniku jako individua. I když se úspěšně propracováváme k porozumění, co je nám dáno do vínku v podobě zděděných genetických informací, stále máme příliš veliký zmatek v hodnocení toho, co na nás působilo během našeho života a jen málo víme, jaký měl ten který vliv význam. Proto jakákoliv predikce toho, co nás čeká a nemine, by měla být omezena na „nesporné“ situace a v každém případě – tzv. vysoce kvalifikovaná a odpovědná.
Human phenotype is governed by its genotype – a set of genetic information materialized in DNA. Using traditional terminology we speak about a little more than 20 thousands genes that differ in strength to become realized and their effect is modified by a large number of other genes. The result originates from firmly established programmes we obtained from our ancestors. Development and activity of such molecules selected for maintenance, copying and transfer of information i.e. nucleic acids can be followed back to the very origin of the life. Nevertheless the final result is achieved not only by confrontation of the original information with other genetic information but largely also by external influences – environment. Though we are relatively successful in understanding what we have inherited from our parents, our knowledge of environmental factors and their effects on formation of the phenotype is still limited. From this point of view medical prediction has always to be very cautious and interpretations at the probability level must be done by a very experienced and responsible professional. Key words: genome, genotype, phenotype, toxicogenomics, epigenetics, mutation, penetrance, pleiotropy, monogenic inheritance, multifactorial inheritance, genetic risk.
- Keywords
- DNA genom, toxikogenomika, epigenetika, pleiotropie, monogenní dědičnost, genetické riziko,
- MeSH
- Heredity MeSH
- DNA MeSH
- Epigenomics MeSH
- Phenotype MeSH
- Financing, Organized MeSH
- Genetic Pleiotropy MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Testing ethics methods utilization MeSH
- Genome MeSH
- Genotype MeSH
- Gene-Environment Interaction MeSH
- Genetics, Medical methods trends MeSH
- Humans MeSH
- Multifactorial Inheritance MeSH
- Mutation MeSH
- Penetrance MeSH
- Toxicogenetics MeSH
- Environment MeSH
- Check Tag
- Humans MeSH
