Genom, transkriptom in proteom

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1 Genom, transkriptom in proteom

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6 The conceptual relationship of the genome, transcriptome, proteome and metabolome

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9 Fenotipi/Phenotypes Morphological phenotypes are fixed in distinct dog breeds.

10 Fizikalna struktura genoma (Physical structure of genome)

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12 Hierarchies of Genome Organization. The hierarchical process by which eukaryotic double-stranded DNA (two meters long, in the case of humans) is packaged within the confines of a micrometers-sized cell. As shown schematically in the figure, this process encompasses three main organization levels classified as primary, secondary and tertiary.

13 An integrated map of human chromosome X. Markers are listed in the centre column, with genetic distances given on the left in centimorgans (cm) and physical distances given on the right in centirays (cr). A BAC-based physical map of the Drosophila buzzatii genome.

14 A genetic map is a type of chromosome map that shows the relative locations of genes and other important features. The map is based on the idea of linkage, which means that the closer two genes are to each other on the chromosome, the greater the probability that they will be inherited together. By following inheritance patterns, the relative locations of genes along the chromosome are established. A physical map of a chromosome or a genome that shows the physical locations of genes and other DNA sequences of interest. Physical maps are used to help scientists identify and isolate genes by positional cloning.

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16 From Primary Sequence to Genome Output. The hard-wired primary information contained in the genome sequence is modulated at short or long timescales by several molecular and cellular events. Modulation may lead to activation (green) or silencing (red) of genome regions.

17 Genomske komponente /Genome components

18 The main components of human genome. The figure provides a summary of the different components of the human genome. Less than 1.5% of the genome consists of the suspected 20,000 25,000 protein-coding sequences. By contrast, a large majority is made up of non-coding sequences such as introns (almost 26%) and (mostly defunct) transposable elements (nearly 45%). A visual history of the estimates of the number of genes in the human genome.

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21 TRANSPOZICIJSKI ELEMENTI (TRANSPOSABLE ELEMENTS) A schematic representation of major classes of transposable elements, including nonautonomous elements. Mammalian transposon families. Only a small proportion of members of any of the illustrated transposon families may be capable of transposing; many have lost such a capacity after acquiring inactivating mutations, and many are short truncated copies. Subclasses of the four main families are listed, along with sizes in base pairs. ORF, open reading frame.

22 Functional diversity of RNA

23 Types of ncrnas

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26 Humani proteom (Human proteome)

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28 Modelni organizmi (Model organisms)

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32 Kakšen je pomen genomskih projektov?

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45 Benefits of genomics data for a broad range of activities, from basic research to clinical applications.

46 In Battelle s interview with Lee Hood he called the HGP the single most transformative event in the history of biological science. Dr. Leroy Hood speech at Russ Prize award, 2011 on the Impact of the Human Genome Project Let me cite briefly 14 genome project accomplishments that revolutionized both biology and medicine. -First, it democratized genes, that is, it made all genes accessible to all biologists. -Second, it delineated for the first time all human genes, and by inference, all proteins. This comprehensive parts list enabled a new approach to biology that I termed systems biology, which takes a holistic approach to dealing with biological complexity. This is the focus of my Institute for Systems Biology the first systems biology organization that was started in Third, it catalyzed the development of high throughput instrumentation, the very effective generation of biological information in genomics, in proteomics (the study of proteins), in metabolomics (the study of small molecules) and in phenotypic assays. -Fourth, it pioneered the applications of computer science and mathematics to biology. In fact, it was the genome project that legitimately brought mathematicians and computer scientists and even theoretical physicists into biology to think about acquiring and storing, analyzing, mining, integrating, and ultimately creating predictive and actionable models of complex biological systems.

47 -Fifth, it was the first biological project whose policy was open source for all data; it demanded the instantaneous release of data to the biological community so everyone could analyze this new information immediately as it was produced. -Sixth, it created the first rigorous standards for biological data and project funding depended on meeting these standards. -Seventh, it gave us access to the genomes of plants, of animals, of microbes, and knowledge of those genomes has transformed many fields of biology. -Eighth, it revolutionized our understanding of evolution in absolutely magnificent ways. -Ninth, it transformed how we think about medicine. It created a new field of medical diagnostics using biomarkers in tissues and blood that can actually detect disease early and stratify complex diseases into their different subtypes so physicians can do impedance matches against appropriate therapies. -Tenth, it also opened up the possibility of using DNA sequencing to identify genes that have actionable behaviors with regard to patients. For example, a gene defect termed Leiden factor 5 leads to an increased tendency for blood clotting. Patients with this defect can drink lots of water, not sit on airplanes for 5 hours without walking and stretching and even use low doses of anti coagulants. This is particular important for pregnant women with the defective gene. -Eleventh, physicians are now using DNA sequencing of tumors to look at disease perturbed biological networks to determine the right drug for the patient. -Twelfth, the genome project created a scientific environment that in part led to the third paradigm change that I will discuss shortly P4 Medicine. (Predictive, Preventive, Personalized and Participatory).

48 -Thirteenth, the genome project has changed the sociology of biology. For example, it introduced the concept of big science to biology. By big science I mean cross disciplinary, hypothesis driven science that integrates different data types to build predictive models to attack hard biological problems such as P4 Medicine. Small science is done by a single investigator and a few co workers and takes on highly focused and discrete problems. The synergy between big and small science is enormous in that each can take advantage of the strengths of other and they can effectively operate in an integrated manner. Unfortunately, at NIH today, there is a thrust to do away with big science (driven by budget constraints and many scientists who practice small science). To eliminate big science would be a tragic mistake, as it is necessary to attack many of the most complex and challenging problems of biology and society today. We obviously need a mixed portfolio where the strengths of big and small science can be utilized together in an integrated manner. -Finally, the genome project also was the first that supported an investigation of the social, ethical, and legal aspects of the genome sequence in a way that presaged how we are really going to have to consider medicine of the future. One of the key realizations that must be understood regarding the human genome sequencing is that its usefulness is perpetual. While other major big science projects have a life attached to them (the $11 billion Superconducting Super Collider has an estimated life span of 30 years for example, or the $1.5 billion Hubble Space Telescope at years), the human genome sequence does not wear out or become obsolete. Rather, the reference human genome is more akin to chemistry s periodic table, a fundamental platform for understanding and advancement of science.