GENETIKA Jelena Bošković i Vasilije Isajev Izdanje Megatrend Univerzitet, Beograd 2007

U ovom udžbeniku su izloženi osnovni rezultati do kojih je savremena nauka došla u svetu i kod nas. Autori nisu imali pretenziju da izlože kompletnu osnovu i sve procese nasleđivanja, već da u sažetoj formi navedu najopštije elementarne principe. Izbor materije i način izlaganja nosi subjektivan pečat, što je sasvim razumljivo kada se ima u vidu da je savremena genetika kao jedna od najpropulzivnijih oblasti.
Prvo izdanje ovog udžbenika je, prema svom sadržaju i rasporedu materije, u osamnaest poglavlja prilagođeno nastavnim programima predmeta GENETIKA, koji se predaje na osnovnim, masters i doktorskim studijama na većem broju Fakulteta u Srbiji - Biološkim, Poljoprivrednim, Medicinskim, Veterinarskim i Šumarskom. Smatramo da će knjiga biti od pomoći i nastavnicima srednjih škola u ostvarivanju njihovih nastavnih pograma, koji jednim delom sadrže i materiju iz osnovnih oblasti genetike.
S obzirom na to, da genetska istraživanja kod nas u nizu područja imaju dinamičan tok razvoja, kao i to da su primene rezultata dobijenih u istraživanjima genetičara velike, smatramo da opšta genetika ne treba da bude samo teoretska, zbog čega su u tekstu predstavljeni i rezultati primenjenih genetskih principa i zakonitosti u biljnoj i životinjskoj proizvodnji, medicini, biotehnologiji.
U pojedinim poglavljima knjige date su osnove za primenu statističkih metoda u genetičkim istraživanjima, kao i veći broj primera, s ciljem boljeg razumevanja materije i većem osamostaljenju u radu onih koji ulažu napore da ovladaju ovim znanjima.

IZVODI IZ RECENZIJE
…….U knjizi su detaljno, razumljivo i na visokom profesionalnom nivou objašnjeni procesi nasleđivanja osobina živih organizama, od mikroorganizama do čoveka kao najvišeg stepena razvoja u evoluciji, što može da otkloni niz dilema u svakodnevnom životu populacije, bez obzira na to o kojem tipu organizma se radi. Poseban aspekt razumevanja nasledne osnove osobina i mehanizma njihovog ispoljavanja obavezuje sve uključene u proces obrazovanja na poštovanje etičkih principa kako u pripremi nastavnih programa, tako i tokom realizacije tih programa. Bioetika je oblast koja kao osnovu ima biološke principe, posebno u oblasti genetike.
Saznanja koja su prikazana u knjizi, i njihova interpretacija, stvaraju preduslove da studenti principe etike poštuju u celini, na način kako to autori udžbenika čine. Na osnovu navedenog, mislim da udžbenik GENETIKA autora prof. Jelene Bošković, uključene aktivno u nastavu na Megatrend univerzitetu, i prof. Vasilija Isajeva, redovnog profesora Univerziteta u Beogradu, zadovoljava sve kriterijume kvaliteta neophodnog u izvođenju nastave, uz posebnu napomenu da autori poseduju široko obrazovanje ne samo u osnovnim istraživanjima nego i u izvođenju eksperimenata, što je presudan uslov prilikom preciznog određivanja veoma visokog ciljnog nivoa znanja kako onih koji tek uče, tako i onog dela populacije koja koristi stečena i stalno uči kako da koristi nova znanja u profesionalnom radu.
Dr Kosana Konstantinov,
naučni savetnik

…………….Udžbenik GENETIKA, autora prof. dr Jelene Z. Bošković i prof. dr Vasilija V. Isajeva, čiji je izdavač Megatrend univerzitet, Beograd, organizovan je u 16 gradivnih poglavlja i tri posebne jedinice - iscrpan popis korištene literature (ukupno 344 jedinice), dvojezični, englesko–srpski rečnik (na ukupno 125 strana) i indeks pojmova. Rukopis u potpunosti zadovoljava, a često i prevazilazi obim nastavnog programa genetike na osnovnim, master i doktorskim studijama na većem broju fakulteta u Srbiji - biološkim, poljoprivrednim, medicinskim, veterinarskom i šumarskom. Autori su u pisanju ovog udžbenika ostvarili savršenu organizaciju gradiva i način izlaganja stručnog teksta. Korišćena terminologija je jasna i razumljiva, a činjenice, definicije i pojmovi su bazirani na principima naučnosti i objektivnosti. Materija koja se obrađuje u knjizi interpretirana je na najsavremeniji način, uz često korištenje primarnih izvora, o čemu svedoči i impresivan broj referenci naveden u popisu korištene literature. Ovakav pristup potvrda je najvišeg ekspertskog nivoa autora. Otuda se, prema poznavanju i korištenju naučnih publikacija, te uvrštavanju najnovijih saznanja u sva poglavlja ovaj udžbenik nesumnjivo svrstava u sam vrh svetske udžbeničke literature.
Prof. dr Aleksandar Ivanc

SADRŽAJ

UVOD                                                                                                                                     17

1.1 Pregled razvoja genetike                                                                                             17

1.2 Genetika i biologija                                                                                                      23

1.3 Naučne discipline genetike                                                                                        25

1.4 Genotip i fenotip                                                                                                            27

1.5 Genetika i organizam                                                                                                   27

1.6 Genetika i čovek                                                                                                            28

1.7 Eksperimentalna genetika                                                                                         31

1.8 Ljudski odnos prema svetu i genetika                                                                     32

1.9 Rezime                                                                                                                           32

2. CITOGENETIKA                                                                                                                35

2.1 Struktura i funkcija ćelija                                                                                             35

2.2 Jedro – nosioc genetičkih informacija                                                                     37

2.3 Jedarce - nukleolus                                                                                                     39

2.4 Hromozomi                                                                                                                    40

2.4.1 Vidljivi hromozomski znaci                                                                                      43

2.4.2 Hemijski sastav hromozoma eukariota                                                                46

2.4.3 Organizacija genetičkog materijala kod prokariota                                            51

2.4.4 Trodimenzionalna struktura nuklearnih hromozoma                                         52

2.5 Deobe ćelije i oplodnja                                                                                               54

2.5.1 Mitoza – kariokineza (ekvaciona deoba)                                                               54

2.5.2 Mejoza                                                                                                                         56

2.6 Crossing – over                                                                                                            60

2.6.1 Mape vezivanja                                                                                                           61

2.6.2 Mapiranje primenom trihibridnog test ukrštanja                                                 63

2.6.3 Interferencija                                                                                                              65

2.6.4 Primeri mapa povezanosti                                                                                      66

2.6.5 Test . 2                                                                                                                         66

2.6.6 Mitotički krosing – over                                                                                             68

2.6.7 Mehanizam krosing – overa                                                                                    68

3. REKOMBINACIJA GENA                                                                                                 71

3.1 Rekombinacija unutar gena                                                                                       71

3.2 Rekombinacija između gena                                                                                     72

3.3 Nezavisno kombinovanje gena                                                                                  73

3.4 Samooplodnja dihribrida                                                                                            75

4. CITOPLAZMA                                                                                                                   77

4.1 Endoplazmatični retikulum                                                                                         77

4.2 Goldžijev kompleks                                                                                                      78

4.3 Ribozomi                                                                                                                        79

4.4 Mikrotubule                                                                                                                    80

4.5 Mitohondrije                                                                                                                   81

4.6 Lipozomi                                                                                                                         81

4.7 Plastidi                                                                                                                            81

4.8 Mehanizam za programirano izumiranje ćelije (Apoptozis)                                 82

4.8.1 Kaspaze                                                                                                                      82

4.8.2 Kontrolisanje proliferacije ćelije i mehanizam odumiranja                              83

4.8.3 Unutarćelijski signali                                                                                                83

5. RAZVIĆE ORGANIZMA I GENETIČKI MATERIJAL – ONTOGENETIKA                    85

5.1 Genetička kontrola morfo – fiziološke diferencijacije                                            85

5.2 Genetička kontrola procesa metabolizma                                                               87

5.3 Priroda veze između gena i biohemijskih reakcija                                                 90

5.4 Ontogenetska adaptacija                                                                                            90

5.5 Ćelija i diferencijacija                                                                                                  91

5.5.1 Genetička kontrola diferencijacije ćelija                                                               91

5.6 Tkivo i diferencijacija                                                                                                    94

5.6.2. Hibridizacija somatskih ćelija                                                                                95

5.7 Genetski materijal u diferencijaciji                                                                            95

5.8 Regulacija genetičke aktivnosti u toku razvića višećelijskih organizama          96

6. TRANSMISIONA GENETIKA                                                                                           99

6.1 Odnosi feno – i genotipova u hibridnom potomstvu                                              99

6.2 Korišćenje ukrštanja – hibridizacije - kao metoda genetičke analize                 99

6.3 Monohibridno nasleđivanje pri potpunom dominiranju                                        100

6.4 Analizirajuće i povratno ukrštanje                                                                              102

6.5 Monohibridno nasleđivanje pri nepotpunom dominiranju                                  103

6.6 Segregacija spora i tetradna analiza                                                                        105

6.7 Uzroci odstupanja odnosa fenotipova kod hibridnih ukrštanja                           107

6.8 Dihibridno nasleđivanje pri potpunom dominiranju                                              107

6.9 Test ukrštanje dihibrida                                                                                              110

6.10 Izračunavanje fenotipskih i genotipskih odnosa za nezavisno razdvajanje gena 111

6.11 Citološke osnove segregacije                                                                                 112

6.12 Polihibridno nasleđivanje pri potpunom dominiranju osobina                        113

6.13 Značaj Mendelovih otkrića za biologiju                                                                114

6.14. Interakcija naslednih osnova                                                                                  116

6.14.1 Komplementarno dejstvo gena                                                                           117

6.14.2 Plejotropija                                                                                                               119

6.14.3 Epistaza                                                                                                                    120

6.14.4 Modifi kaciono delovanje gena                                                                             120

6.14.5 Nasleđivanje kvantitativnih osobina                                                                    121

6.14.6 Genski balans                                                                                                         124

7. NASLEĐIVANJE POLA                                                                                                    125

7.1 Obrazovanje polnih ćelija kod biljaka                                                                       127

7.1.1 Mikrosporogeneza i obrazovanje muškog gametofita                                       127

7.1.2 Makrosporogeneza i obrazovanje ženskog gametofita                                     128

7.2 Oplođenje kod biljaka                                                                                                  129

7.2.1 Mehanizam oplođenja golosemenica (Gymnospermae)                                 130

7.2.2 Mehanizam oplođenja skrivenosemenica (Angiospermae)                            131

7.3 Spermato – i oogeneza kod životinja                                                                        134

7.4 Raznovrsnost i zastupljenost polova kod cvetnica                                                 134

7.5 Mehanizmi genetičke determinacije pola                                                                137

7.6 Hromozomsko objašnjenje mehanizma determinacije pola                              138

7.7 Determinacija pola i partenogeneza kod opnokrilaca                                          142

7.8 Genski balans i određivanje pola po K. Bridžesu                                                  142

7.9 Fiziološka determinacija pola po R. Goldšmitu                                                     144

7.10 Diferencijacija i promena pola                                                                                  145

7.11 Značaj polnog procesa                                                                                             146

7.12 Genetičke karakteristike polnosti kod ljudi                                                           147

7.13 Specifi čni primeri determinacije pola                                                                   149

7.14 Nasleđivanje vezano za polne hromozome                                                          150

7.15 Nasleđivanje pod uticajem pola i ograničeno polom                                         151

8. VANHROMOZOMSKO ILI EKSTRANUKLEARNO NASLEĐIVANJE        153

8.1 Uloga citoplazme u vanhromozomskom nasleđivanju osobina                         154

8.2 Uloga plastida u vanhomozomskom nasleđivanju                                               155

8.3 Uloga drugih organela u vanhromoZomskom nasleđivanju                               158

8.4 Izazivanje vanhromozomskih promena                                                                    160

8.5 Značaj ekstranuklearnog nasleđivanja                                                                    161

9. OSNOVE BIOHEMIJSKE GENETIKE                                                                             163

9.1 Građa i funkcija nukleinskih kiselina                                                                        163

9.1.1 Hershey – Chase eksperiment                                                                              164

9.2 Replikacija (udvajanje, reprodukcija) DNK                                                             166

9.3 Infrastruktura DNK                                                                                                        167

9.3.1 Ukupna količina DNK                                                                                               168

9.3.2 Nukleinske kiseline mitohondrija                                                                          168

9.3.3 Nukleinske kiseline plastida                                                                                  168

9.4 Transkripcija RNK po obrascu DNK                                                                         169

9.4.1 Genetički kod                                                                                                             169

9.4.2 Transkripcija - sinteza RNK                                                                                    171

9.5 Tipovi RNK                                                                                                                     175

9.5.1 Informaciona (messenger) RNK                                                                           175

9.5.2 Transportna (transfer) RNK                                                                                    176

9.5.3 Ribozomalna RNK – rRNK                                                                                      178

9.6 Sinteza proteina                                                                                                            180

9.7 Struktura proteina                                                                                                         182

9.8 Translacija                                                                                                                     183

9.8.1 tRNK sa komplementarnom sekvencom prevodi kodon u aminokiselinu.   183

9.8.2 Ribozomi – fabrike proteina                                                                                    185

9.9 Funkcija proteina i greške u ćeliji                                                                              187

9.9.1 Funkcija enzima                                                                                                        187

9.9.2 Greška u funkcionisanju alela                                                                                                189

9.9.3 Kolinearnost gena i proteinske strukture                                                             192

9.10 Uzrok genetskih oboljenja kod ljudi                                                                       193

9.11 Defektni proteini i dominantnost i recesivnost                                                     194

9.12 Funkcionalna podela rada u setu gena                                                                                 195

9.13 Rezime                                                                                                                         197

10. MUTACIJE                                                                                                                      199

10.1 mutacije broja hromozoma                                                                                      201

10.1.1 Aneuploidija (heteroploidija)                                                                                                201

10.1.2 Haploidija                                                                                                                                 206

10.2 Mutacije strukture hromozoma                                                                                207

10.2.1 Delecije i duplikacije                                                                                              207

10.2.2 Translokacije                                                                                                           210

10.2.3 Inverzije                                                                                                                     213

10.3 Molekularna osnova mutacije                                                                                  215

10.3.1 Promene na nivou DNK                                                                                         216

10.4 Mehanizmi indukovanja mutacije                                                                            218

10.5 Mehanizmi spontanih mutacije                                                                               223

10.6 Analiza mutacija                                                                                                         228

10.6.1 Somatske i germinalne mutacije                                                                        228

10.6.2 Mutacije unapred i unazad                                                                                    230

10.6.2 Mutant fenotipovi                                                                                                     230

10.7 „P” elementi                                                                                                                 231

10.8 Retrovirusi                                                                                                                   232

10.9 Kontrolni elementi - transpozoni kod kukuruza                                                    232

10.10 Eksperimenti Barbare MCClintock – Ds element                                             233

10.11 Lokus Wx                                                                                                                   235

10.12 Opšte karakteristike kontrolnih elemenata (transpozona)                              235

10.13 Pregled mobilnih elemenata kod eukariota                                                       236

10.14 Rezime                                                                                                                       237

11. MEHANIZMI IMUNOLOŠKE REAKCIJE                                                      239

11.1 Genetička kontrola sinteze imunoglobulina                                                         239

11.2 Teorije o obrazovanju antitela                                                                                  241

11.3 Imunogenetika krvnih grupa kod čoveka                                                               242

11.3.1 ABO sistem                                                                                                              243

11.3.2 Rh, MN i Ss sistemi                                                                                                243

11.3.3 Krvne grupe i bolesti                                                                                              245

11.4 Genetičke osnove transplantacije                                                                          247

11.5 Genetička osnova pojave kancera                                                                          248

11.5.1 Molekularna priroda kancera                                                                                249

11.6 Pojava kancera kod biljka                                                                                         254

12. TEHNOLOGIJA REKOMBINANTNE DNK                                                   257

12.1 Dobijanje rekombinantne dnk                                                                                 257

12.1.1. Izolovanje DNK                                                                                                       259

12.1.2 Isecanje DNK                                                                                                          259

12.1.3 Spajanje DNK vektora i fragmenta koji se klonira                                            262

12.2 Amplifi kacija rekombinantne DNK                                                                         262

12.3 Kloniranje specifi čnog gena                                                                                   262

12.3.1 Izbor vektora                                                                                                             264

12.3.2 Formiranje DNK biblioteke                                                                                   267

12.3.3 Identifi kacija gena korišćenjem specifičnih proba                                          269

12.3.4 Identifi kacija specifi čnih klonova funkcionalnom dopunom                         272

12.4 Poziciono kloniranje                                                                                                  274

12.5 Kloniranje gena obeležavanjem                                                                             275

12.6 Korišćenje klonirane DNK kao probe u eksperimentima identifi kacije

specifi čnog segmenta nukleinske kiseline                                                                  276

12.7 Određivanje DNK sekvence                                                                                     279

12.8 Otkrivanje i amplifi kacija sekvenci pomoću PCR – a                                         280

12.9 Lociranje gena na restrikcionim mapama                                                            281

12.10 Genetska ispitivanja alkaptonurije                                                                       285

12.11 Rezime                                                                                                                       285

13. PRIMENA TEHNOLOGIJE REKOMBINANTNE DNK                                                 287

13.1 Mutageneza in vitro                                                                                                    287

13.2 RFLP mapiranje                                                                                                         289

13.3 Rreverzibilna genetika                                                                                               291

13.4 Ekspresija eukariotskih gena u bakterijama                                                        292

13.5 Tehnologija rekombinantne DNK kod eukariota                                                                 293

13.5.1 Transgeni eukariotski organizmi                                                                         294

13.6 Primena genetičkog inženjeringa u pekarskom kvascu                                    295

13.7 Genetički inženjering biljaka                                                                                    298

13.8 Transgene biljke useva                                                                                            301

13.9 Genetički inženjering kod životinja                                                                          302

13.9.1 Oštećenje funkcije i zamena gena kod miševa.                                               304

13.10 Genska terapija                                                                                                        305

13.10.1 Genska terapija kod čoveka                                                                               306

13.11 Pprimena rekombinantne DNK za direktno otkrivanje alela nosioca obolJenja 308

13.11.1 Izmena restrikcionog mesta mutacijom                                                          309

13.11.2 Utvrđivanje postojanja izmenjenih sekvenci                                                   310

13.12 Rezime                                                                                                                       310

14. KVANTITATIVNA GENETIKA                                                                                       311

14.1 Kvantitativna svojstva                                                                                                 316

14.2 Neki osnovni statistički pojmovi                                                                              318

14.3 Distribucije                                                                                                                  319

14.3.1 Statistička merenja                                                                                                                 320

14.3.2 Genotipovi i fenotipska distribucija                                                                     321

14.3.2. Norma reakcije i fenotipske distribucije                                                            324

14.3.3 Određivanje norme reakcije                                                                                                 325

14.4 Genetičke i fenotipske korelacije                                                                            326

14.5 Analiza varijanse i kovarijanse slučajnog blok sistema                                     327

14.6 Heritabilnost i koefi cijenti genetičke i fenotipske varijacije                               335

14.6.1 Procena komponenata genetičke varijanse                                                      336

14.7 Korišćenje h2 u selekciji                                                                                          337

14.8 Genetičke i fenotipske korelacije iz faktorijalnih ogleda                                     338

14.9 Regresija (heritabilnost) roditelj – potomstvo                                                      340

14.10 Linearna višestruka regresija i path coeffi cient                                                341

14.10.1 Path coeffi cient – opšti model                                                                           342

14.10.2 Path coeffi cient – sa dve nezavisno promenljive                                           343

14.11 Analiza efekta gena na osnovu proseka familija                                               346

14.12 Segregacija marker gena                                                                                      349

14.12.1 Analiza ukopčanosti (linkage)                                                                            349

14.13 Inbriding – koefi cijent inbridinga i sistemi Inbridinga                                      350

14.13.1 Inbriding u populaciji                                                                                           352

14.14. Rezime                                                                                                                      353

15. POPULACIONA I EVOLUCIONA GENETIKA                                                              355

15.1 Doprinos Darvinovog učenja razvoju populacione i evolucione genetike       355

15.2 Frekvencija gena i genotipova                                                                                 356

15.3 Varijabilnost i njena prilagodljivost                                                                         358

15.3.1 Proučavanje varijabilnosti                                                                                     358

15.3.2 Proračunavanje frekvencije alela                                                                         359

15.4 Polimorfi zam DNK sekvence                                                                                  361

15.5 Varijabilnost unutar i između populacija                                                               362

15.5.1 Kvantitativna varijabilnost                                                                                      363

15.5.2 Efekat seksualne reprodukcije na varijabilnost                                                364

15.6 Hardy – Weinberg ravnoteža                                                                                    364

15.7 Dominacija i frekvencija gena                                                                                                 369

15.8 Vezani lokusi                                                                                                               369

15.8.1 Polno vezana svojstva                                                                                            369

15.8.2 Multipli aleli                                                                                                              370

15.9 Izvori varijabilnosti                                                                                                      370

15.9.1 Varijabilnost nastala mutacijama                                                                        371

15.9.2 Efekat mutacije na frekvenciju alela                                                                    371

15.9.3 Varijabilnost nastala rekombinacijama                                                             372

15.9.4 Varijabilnost nastala migracijom gena                                                              373

15.9.5 Efekti migracije na frekvenciju alela                                                                    374

15.9.6 Poreklo novih funkcija                                                                                            374

15.10 Promene frekvencije gena u populaciji                                                               374

15.10.1 Mutacije                                                                                                                  375

15.10.2 Selekcija                                                                                                                 377

15.10.3 Ekvilibrijum između mutacije i selekcije                                                          383

15.10.4 Migracija                                                                                                                 384

15.11 Genetsko opterećenje i genetička smrt                                                              391

15.12 Rezime                                                                                                                       391

16. LITERATURA                                                                                                  393

17. DICTIONARY - REČNIK                                                                                                 409

18. REGISTAR PRILOGA                                                                                    521

19. INDEKS POJMOVA                                                                                                       529