MOLEKULARNA OSNOVA NASLEDJIVANJA
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1 MOLEKULARNA OSNOVA NASLEDJIVANJA
2 Osnovne karakteristike genetičkog materijala čuvanje genetičke informacije u strukturi DNK Samoudvajanje kroz replikaciju Sposobnost kontrole fenotipa kroz sintezu proteina promenljivost putem mutacija Zašto DNK?
3 struktura
4 Baze: purini (adenin i guanin) pirimidini (timin i citozin) (uracil) Fosfatna grupa Pentozni šećer nukleotidi Makromolekuli, DNK i RNK DNK - dvostruki polinukleotidni lanac
5 Homo sapiens, mlada vrsta Ljudi na nivou nukleotida imaju oko 98,8% sličnosti sa šimpanzama, a jedinke unutar vrste Homo sapiens medjusobno se razlikuju u proseku u 1/ nukleotida.
6 Organism Genome Size (Bases) Estimated Genes Human (Homo sapiens) 3 billion 30,000 Laboratory mouse (M. musculus) 2.6 billion 30,000 Mustard weed (A. thaliana) 100 million 25,000 Roundworm (C. elegans) 97 million 19,000 Fruit fly (D. melanogaster) 137 million 13,000 Yeast (S. cerevisiae) 12.1 million 6,000 Bacterium (E. coli) 4.6 million 3,200 Human immunodeficiency virus (HIV)
7 JEDARNA DNK 3.2 Gb VANGENSKA DNK 75% GENSKA DNK 25% kodirajući i regulatorni Regioni 1.5% nekodirajući Regioni 23.5% satelitska DNK 5% mt DNK 16.5kb tandemski Ponovci 9% mikro Sateliti 1% mini Sateliti 3% ponavljajuća DNK 54% SINE 13% LINE 21% UNIKATNE KOPIJE 21% rasuti Ponovci 45% LTR 8% DNKtrans pozoni 3% Klasifikacija humanog genoma i DNK sekvenci prema strukturi i funkciji
8 replikacija osnovne osobine Semikonzervativnost Komplementarnost neophodno RNK prajmer DNK polimeraza III (5 3 )
9 kod eukarioita Više početaka replikacije
10
11 Lančana reakcija polimeraze
12 Pol III 5 3 polimerizacija Pol III 3 5 editovanje, tj. provera čitanja
13 kraj replikacije kod eukariota - telomere -kraj replikacije uklanjanje RNK prajmera -5 praznina -enzim telomeraza, RNK enzim -sinteza trinukleotida na DNK na osnovu RNK templeta -ponavljanje sinteze -ligazom i polimerazom se sintetiše DNK na osnovu dodatog RNK prajmera -ukloni se prajmer -hromozom je sačuvao dužinu
14 ekspresija gena do ishoda - fenotipa genom ćelija hromozomi geni DNK proteini Proteini deluju pojedinačno ili udruženo u kompleksu u obavljanju različitih ćelijuskih funkcija Geni sadrže instrukcije za stvaranje proteina
15 ekspresija gena do ishoda - fenotipa Trilioni ćelija u organizmu, na primer, čoveka Svaka ćelija po 46 hromozoma = 2m DNK 3 milijarde subjedniica (baza A,T,G,C) Oko gena kodira za proteine osnovnih životnih funkcija ćelija
16
17
18 KOD KODON ANTIKODON DNK i-rnk t-rnk POLIPEPTID ekspresija gena do ishoda - fenotipa
19
20
21 Stuktura gena eukariota egzoni introni
22 Genske familije aktini, globini, miozin, proteini jajeta, Ig,...
23 Tandemske genske familije Histoni, geni za r-rnk (organozator nukleolusa), t-rnk,
24 TRANSKRIPCIJA
25 promotor gena prokariota i eukariota RNK polimeraza se vezuje za promotor Prepoznajući konsenzus sekvence duž DNK...
26 Transkripcija sinteza RNK molekula 3 osnovna tipa RNK molekula translacija sinteza polipeptida
27 GENETIČKI KOD (ŠIFRA) UNIVERZALNOST IZROĐENOST NEPREKLAPANJE KONTINUIRANOST
28 Translacija
29 različiti nivoi regulacije ekspresije gena kod eukariota
30 postgenomska era više nema tehničkih barijera za dobijanje informacija o genomu izazov razumevanje proteoma, transkriptoma, metaloboma... teško polje istraživanja - nedostaju metode za potpuno deifnisanje Svaka ćelija ima isti genom, istu DNK sekvencu sa kojom se radja, ali svaka ćelija u telu ima drugačiji proteom, a on se menja i kroz vreme. Ex:Pri infekciji, proteom se menja u ćelijama, kao imuni odgovor. Lekovi, vežbanje, ishrana..proteomi se menjaju kao odgovor na fluktuacije i unutarćelijskoj i medjućelijskoj sredini. Prelaz sa klasičnog razmišljanja jedan gen - jedan protein - jedan fenotip na razumevanje složenih fenotipova
31 Promenljivost genetičkog materijala Mutacije promene u genima, hromozomima slučajni dogadjaji spontane / indukovane germinativne/somatske nasledne kroz generacije u populacijama nastanak tumora karcinogeneza delovanjem agenasa, mutagena
32 DNK SEKVENCA OSOBA 1 NORMALNI PROTEIN OSOBA 2 NEFUNKCIONALNI PROTEIN OSOBA 3 IZMENJENI PROTEIN DOVODI DO POREMEĆAJA, OBOLJENJA
33 spontane mutacije tokom replikacije tautomerni oblici
34 tranzicije transverzije
35 bez efekta na fenotip - tihe - DNK polimorfizmi - neutralne sa efektom na fenotip na nivou translacije proteina nonsens zaustavljanje translacije misens zamena amino kiseline frameshift - promena celog polipeptida
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