Genom, transkriptom in proteom

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

Fenotipi/Phenotypes

Morphological phenotypes are fixed in distinct dog breeds.

Fizikalna struktura genoma (Physical structure of genome)

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. Asshown schematically in the figure, this process encompasses three main organization levels classified asprimary, secondary and tertiary.

An integrated map of human chromosome X.Markers are listed in the centre column, withgenetic distances given on the left incentimorgans (cM) and physical distances given onthe right in centirays (cR).

A BAC-based physical map of the Drosophila buzzatiigenome.

A physical map of a chromosome or a genome thatshows the physical locations of genes and other DNAsequences of interest. Physical maps are used to helpscientists identify and isolate genes by positionalcloning.

A genetic map is a type of chromosome map thatshows the relative locations of genes and otherimportant features. The map is based on the idea oflinkage, which means that the closer two genes are toeach other on the chromosome, the greater theprobability that they will be inherited together. Byfollowing inheritance patterns, the relative locationsof genes along the chromosome are established.

From Primary Sequence to Genome Output. Thehard-wired primary information contained in thegenome sequence is modulated at short or longtimescales by several molecular and cellular events.Modulation may lead to activation (green) orsilencing (red) of genome regions.

Genomske komponente /Genome components

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.

A schematic representation of major classes of transposableelements, including nonautonomous elements.

Mammalian transposon families. Only a small proportion ofmembers of any of the illustrated transposon families may becapable of transposing; many have lost such a capacity afteracquiring inactivating mutations, and many are short truncatedcopies. Subclasses of the four main families are listed, alongwith sizes in base pairs. ORF, open reading frame.

TRANSPOZICIJSKI ELEMENTI

(TRANSPOSABLE ELEMENTS)

Functional diversity of RNA

Types of ncRNAs

Humani proteom (Human proteome)

Modelni organizmi (Model organisms)

Kakšen je pomen genomskih projektov?

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

In Battelle’s interview with Lee Hood he called the HGP “the single most transformative event in the history ofbiological 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 “partslist” enabled a new approach to biology that I termed “systems biology”, which takes a holistic approach to dealingwith biological complexity. This is the focus of my Institute for Systems Biology—the first systems biologyorganization that was started in 2000.-Third, it catalyzed the development of high‐throughput instrumentation, the very effective generation ofbiological information in genomics, in proteomics (the study of proteins), in metabolomics (the study of smallmolecules) and in phenotypic assays.-Fourth, it pioneered the applications of computer science and mathematics to biology. In fact, it was the genomeproject that legitimately brought mathematicians and computer scientists and even theoretical physicists intobiology to think about acquiring and storing, analyzing, mining, integrating, and ultimately creating predictiveand actionable models of complex biological systems.

-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).

-Thirteenth, the genome project has changed the sociology of biology. For example, it introduced the concept ofbig science to biology. By big science I mean cross‐disciplinary, hypothesis‐driven science that integrates differentdata types to build predictive models to attack hard biological problems such as P4 Medicine. Small science isdone by a single investigator and a few co‐workers and takes on highly focused and discrete problems. The synergybetween big and small science is enormous in that each can take advantage of the strengths of other and they caneffectively operate in an integrated manner. Unfortunately, at NIH today, there is a thrust to do away with bigscience (driven by budget constraints and many scientists who practice small science). To eliminate big sciencewould be a tragic mistake, as it is necessary to attack many of the most complex and challenging problems ofbiology and society today. We obviously need a mixed portfolio where the strengths of big and small science can beutilized together in an integrated manner.-Finally, the genome project also was the first that supported an investigation of the social, ethical, and legalaspects of the genome sequence in a way that presaged how we are really going to have to consider medicine ofthe future.

One of the key realizations that must be understood regarding the human genome sequencing is that itsusefulness is perpetual. While other major big science projects have a life attached to them (the $11 billionSuperconducting Super Collider has an estimated life span of 30 years for example, or the $1.5 billion Hubble SpaceTelescope at 15–20 years), the human genome sequence does not wear out or become obsolete. Rather, thereference human genome is more akin to chemistry’s periodic table, a fundamental platform for understandingand advancement of science.