Human Genome Organization*
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Nedávné zveřejnění předběžné sekvence lidského genomu a její první analýzy přinesly několik překvapivých zjištění. Lidský genom obsahuje pouze kolem 42 000 genů a nikoliv 100 000, jak se dlouho předpokládalo. Srovnání s dalšími sekvenovanými genomy naznačuje, že komplexity organizmu nemusí být dosahováno zvyšováním počtu genů, ale že může být založena na regulačních mechanizmech spojených s alternativní expresí genů a na složitých interakcích genů a/nebo jejich proteinových produktů. Pokroky genomiky a příbuzných moderních oborů začínají podstatně měnit biomedicínský výzkum a samotnou medicínu, kde se zájem přesouvá zejména k multifaktoriálním chorobám. Nové poznatky postupně povedou k mnohem efektivnější diagnostice, přesné prognóze průběhu chorob a prognóze odpovědi jedince na léky, cílené terapii s využitím nových farmak i terapie genové a především k cílené prevenci založené na detailní znalosti individuální predispozice k chorobám.
Recent publication of the working draft of the human genome and its first analyses revealed several surprising findings. The human genome contains only about 42 000 genes, contrary to previous estimates of about 100 000. Comparison with other genomes suggests that the complexity of an organism neednot result from increasing gene number, but it can be based on regulatory mechanisms associated with alternative gene expression and on complex interactions of genes and/or their protein products. The progress in genomics and related modern disciplines is influencing substantially the biomedical research and the medicine itself, where the main focus shifts towards multifactorial diseases. The new knowledge will lead to much more effective diagnosis, exact prognosis of the disease course and of individual drug response, to the targeted therapy using new drugs and gene therapy, and mainly towards targeted prevention based on the detailed knowledge of individual disease predisposition.
- MeSH
- genomová knihovna MeSH
- projekt Lidský genom MeSH
- rekombinantní DNA MeSH
- Publikační typ
- přehledy MeSH
[1st ed.] xiv, 330 s. : il.
xxii, 1135 s., [32] s. obr. příl. : il., tab., grafy ; 30 cm
If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings-so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.
- MeSH
- genetické testování etika normy MeSH
- genetika člověka etika organizace a řízení normy MeSH
- lidé MeSH
- směrnice pro lékařskou praxi jako téma * MeSH
- společnosti lékařské normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
... -- An overview of human genetic variation -- Human population genetics -- Comparative genomics and genome ... ... -- Pt. 5: Applied human molecular genetics -- Genetic testing in healthcare and the law -- Model organisms ... ... GENOME 279 -- 9.1 An overview of the human genome 279 -- 9.2 Gene organization and distribution in the ... ... human genome 296 -- 9.3 Heterochromatin DNA and transposon repeats 306 -- 9.4 A start on working out ... ... EVOLUTION 461 -- 14.1 Human origins 461 -- 14.2 Human evolutionary history from genome sequences 467 ...
Fifth edition xiii, 770 stran : ilustrace ; 29 cm
3rd ed. 674 s.
- Klíčová slova
- Genetika molekulární,
- MeSH
- genom lidský MeSH
- molekulární biologie MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host-microbiome metabolic interactions.
130 s. : il., tab.
Epigenetic marks are important factors regulating the pluripotency and differentiation of human embryonic stem cells (hESCs). In this study, we analyzed H3K9 acetylation, an epigenetic mark associated with transcriptionally active chromatin, during endoderm-like differentiation of hESCs. ChIP-on-chip analysis revealed that differentiation results in a genome-wide decrease in promoter H3K9 acetylation. Among the 24,659 promoters analyzed, only 117 are likely to be involved in pluripotency, while 25 acetylated promoters are likely to be responsible for endoderm-like differentiation. In pluripotent hESCs, the chromosomes with the highest absolute levels of H3K9 acetylation are chromosomes 1, 6, 2, 17, 11, and 12 (listed in order of decreasing acetylation). Chromosomes 17, 19, 11, 20, 22, and 12 are the most prone to differentiation-related changes (both increased acetylation and deacetylation). When chromosome size (in Mb) was accounted for, the highest H3K9 acetylation levels were found on chromosome 19, 17, 6, 12, 11, and 1, and the greatest differentiation-associated decreases in H3K9 acetylation occurred on chromosomes 19, 17, 11, 12, 16, and 1. The gene density and size of individual chromosomes were strongly correlated with the levels of H3K9 acetylation. Our analyses point to chromosomes 11, 12, 17, and 19 as being critical for hESC pluripotency and endoderm-like differentiation. J. Cell. Physiol. 219: 677-687, 2009. (c) 2009 Wiley-Liss, Inc.
- MeSH
- acetylace MeSH
- buněčná diferenciace fyziologie genetika MeSH
- buněčné linie MeSH
- chromatinová imunoprecipitace MeSH
- embryonální kmenové buňky cytologie metabolismus MeSH
- epigeneze genetická MeSH
- financování organizované MeSH
- genom lidský MeSH
- histony genetika chemie metabolismus MeSH
- lidé MeSH
- lidské chromozomy genetika metabolismus MeSH
- pluripotentní kmenové buňky cytologie metabolismus MeSH
- promotorové oblasti (genetika) MeSH
- Check Tag
- lidé MeSH
vi, 138 s. : il., tab.
- MeSH
- chromozomy MeSH
- cytogenetika MeSH
- terminologie jako téma MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Biologické vědy
- NLK Obory
- genetika, lékařská genetika
- biologie
