mutacije
TRANSCRIPT
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BIOLOŠKA PROMENLJIVOST
FENOTIPSKA GENOTIPSKA
=99.9%
MUTACIJE REKOMBINACIJE
GENSKE BOLESTI
EVOLUCIJA
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GENSKE MUTACIJE
TRAJNE, NASLEDNE PROMENE U SEKVENCI DNK
Citogenetski se vidi višak ili manjak 4
Mb
260Mb50
Mb
Genske mutacije se ne vide analizom
kariotipa
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mogu da se dese u bilo kom genu genoma, u bilo koje vreme od embrionalnog razvića do poznih godina života
imaju specifičan efekat
su većinom negativne
su u malom broju pozitivne (faktor evolucije)
mutacije
PREDSTAVLJAJU IZVOR NOVIH OBLIKA GENA - ALELA
su slučajne, nezavisne od efekta koje imaju na nosioca
su važne za preživljavanje vrste
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a a+
OBLIK GENA KOJI JE ŠIROKO RASPROSTRANJEN U PRIRODI PREDSTAVLJA DIVLJI OBLIK GENA
a+
Direktna mutacija
a+ a
D+ D
Povratna (reverzna) mutacija
D D+
Učestalost povratnih manja od direktnih
rekurentne mutacije – promene u isti alelni oblik
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SOMATSKE MUTACIJE
GERMINATIVNE MUTACIJE
- MUTACIJE NASTAJU U GERMINATIVNIM ĆELIJAMA, SPERMATOZOIDIMA I JAJNIM ĆELIJAMA
- PRENOSE SE NA POTOMSTVO
- MUTACIJE NASTAJU U TELESNIM (SOMATSKIM) ĆELIJAMA
- NE PRENOSE SE NA POTOMSTVO
- ORGANIZAM MOZAIK
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retinoblastom
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EFEKAT MUTACIJA NA FENOTIP
IZRAŽAVA SE U RAZLIČITIM PERIODIMA ŽIVOTA
na rodjenju (Tay-Sachs; cistična fibroza)
tokom života (ćelavost, Huntington horea)
SE RAZLIKUJE PO JAČINI
letalan ; dovodi do steriliteta; nema efekta na preživljavanje
SE ISPOLJAVA SAMO POD ODREDJENIM USLOVIMA
temperatura (propustljiva ili ograničavajuća)
pojačivači i supresori
SE ISPOLJAVA POSREDNO - MODIFIKATORI
DOMINANTAN ILI RECESIVAN
G6PD deficijencija
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GENOTIP
GENSKA (ALELSKA) KOMBINACIJA KOJA PREDSTAVLJA GENETSKU KONSTITUCIJU JEDINKE
- U SVIM GENSKIM LOKUSIMA
- SAMO U POJEDINAČNIM LOKUSIMA
A1A1
HOMOZIGOT
A1 A2
HETEROZIGOT
A2 A3
SLOŽENI HETEROZIGOT
A1 DIVLJI (NORMALNI ALEL)
A2 A3 MUTIRANI ALELI
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ALEL
Jedan, dva ili više različitih oblika istog gena koji zauzimaju jedan genski lokus, medjusobno mogu da se razlikuju i po različitom uticaju na fenotip
2 ALELNA OBLIKA GENA A A1 I A2
MOGUĆI GENOTIPOVI
A1 A1
A2 A2
A1 A2
HOMOZIGOT A1
HOMOZIGOT A2
HETEROZIGOT
FENOTIPSKA SKALA
A1 A1 A2 A2
A1 A2 A1 A2A1 A2
A1 dominantan A2 dominantanNema dominacije
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A DOMINANTAN ALEL
a RECESIVAN ALEL
DOMINANTNI HOMOZIGOT HETEROZIGOT
RECESIVNI HOMOZIGOT
FENOTIP
DOMINANTAN
RECESIVAN
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hromozom
hromozom
A A
Aa
a
a
Mutacija dominantna
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Vunasta kosa
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polidaktilijabrahidaktilija
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ahondroplazija
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ahondroplazija
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Familijarna hiperholesterolemija
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holoprozencefalija
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hromozom
hromozom
A
A
A a
aa
Mutacija recesivna
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albinizam
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albinizam
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Duchenne-ova mišićna distrofija
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autozomno dominantno
autozomno recesivno
X vezano recesivno
1966 1975 1986 1992
269 (+568)
237 (+294)
68 (+51)
574 (+913)
1487
583 (+635)
466 (+481)
93 (+78)
1172 (+1029)
2470 (+1241)
647 (+984)
190 (+178)
610 (+810)
124 (+162)
1142 (+1194)
1906 (+2001)
3307 (+2403)
2336 3907 5710ukupno
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http://www.ncbi.nlm.nih.gov/Omim/.
http://www.genetests.org
~ 6000
~ 200 bolesti
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TIPOVI MUTACIJA
SUPSTITUCIJE – zamena jedne baze drugom
tranzicijeA G
T C
transverzije A T A C G T G C
INSERCIJE - umetanje baza
DELECIJE - gubitak baza
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A
C A T C A T C A T C A T C A T
G AT G AT G AT G AT G T
A
C A T C A T A T C A T C A T
G AT G AT AT G AT G T
T
A
SUPSTITUCIJA
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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T C T C A A A A A A GCTTT
A G A G T T T T T T CGAAA
5’...3’... …5’
…3’
T C T C A A G A A A GCTTT
A G A G T T C T T T CGAAA
5’...3’... …5’
…3’
TRANZICIJA (AT GC)
5’...3’... …5’
…3’
5’...3’... …5’
…3’
TRANSVERZIJA (CG GC)
T C T C A A A A A A GCTTT
A G A G T T T T T T CGAAA
T C T G A A A A A A GCTTT
A G A C T T T T T T CGAAA
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…5’3’...
MISSENSE MUTACIJA
T C T C A A A A A T T T A C G
T C T C A A G A A T T T A C G
A G A G T T T T T A A A T G C
A G A G T T C T T A A A T G C
…3’
…3’
…5’
5’...
5’...
3’... Ser Gln Lys Phe Thr ……
…… Ser Gln Glu Phe Thr
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…5’3’...
NONSENSE MUTACIJA
T C T C A A A A A T T T A C G
T C T C A A T A A T T T A C G
A G A G T T T T T A A A T G C
A G A G T T A T T A A A T G C
…3’
…3’
…5’
5’...
5’...
3’... Ser Gln Lys Phe Thr ……
… Ser Gln STOP
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…5’3’...
NEUTRALNA MUTACIJA
T C T C A A A A A T T T A C G
T C T C A A A G A T T T A C G
A G A G T T T T T A A A T G C
A G A G T T T C T A A A T G C
…3’
…3’
…5’
5’...
5’...
3’... Ser Gln Lys Phe Thr ……
…… Ser Gln Arg Phe Thr
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…5’3’...
TIHA MUTACIJA
T C T C A A A A A T T T A C G
T C T C A A A A G T T T A C G
A G A G T T T T T A A A T G C
A G A G T T T T C A A A T G C
…3’
…3’
…5’
5’...
5’...
3’... Ser Gln Lys Phe Thr ……
…… Ser Gln Lys Phe Thr
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A
C A T C A T C A T C A T C A T
G AT G AT G AT G AT G T
A
C A T C A T C A T C A T C A T
G AT G AT G AT G AT G T
G
C
INSERCIJA
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
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A
C A T C A T C A T C A T C A T
G AT G AT G AT G AT G T
DELECIJA
C A T C A
T
G AT G
A
T A
C A T C A T C A T
G AT G AT G T1 2 3 4 5 6 7 8 9 10 11 12 13 14
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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…5’3’...
FRAMESHIFT MUTACIJA (insercija)
T C T C A A A A A T T T A C G
T C T C A A G A A A T T T A C G
A G A G T T T T T A A A T G C
A G A G T T C T T T A A A T G C
…3’
…3’
…5’
5’...
5’...
3’... Ser Gln Lys Phe Thr ……
…… Ser Gln Glu Ile Tyr
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1 2 3 4 5 6 7 8 9 10 11 12
G A T C T A T G G T A T
C AT G TA A CC A AT
NORMALNO
G A U C U A U G G U A U
DNK
iRNK
Asp Leu Trp Tyr protein
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1 2 3 4 5 6 7 8 9 10 11 12
G A C C T A G G G T A T
C GT G TA C CC A AT
missense
G A U C U A G G G U A U
DNK
iRNK
Asp Leu Glu Tyr protein
TIHA
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1 2 3 4 5 6 7 8 9 10 11 12
G A T C T A T A G T A T
C AT G TA A CT A AT
NONSENSE
G A U C U A U A G U A U
DNK
iRNK
Asp Leu protein
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1 2 3 4 5 6 7 8 9 10 11 12
G A C T A T G G T A T
C T G TA A CC A AT
FRAMESHIFT – mutacije pomaka
G A C U A U G G U A U
DNK
iRNK
Asp Tyr Gly Met protein
delecija
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A
Tyr
Tyr
UU
His
Cys
Stop
Phe
U A
Ser
Asp
G A U
Asn
AA U
C A U
UU U
UU G U C U
Stop
C
U A G
U A
A
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Misens - izmenjeni kodon dovodi i do promene aminokiseline
Nonsens – menja kodon za aminokiselinu u stop kodon
Tihe – izmenjeni kodon ne menja aminokiselinu
Neutralne – izmenjeni kodon odredjuje aminokiselinu sličnih osobina
SUPSTITUCIJE – point (tačkaste) mutacije
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POSLEDICE MUTACIJA
(Zavise od mesta gde se desila)
1. Izmenjeni protein
2. Neaktivni protein
3. Prekid sinteze proteina
4. Bez efekta
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HEMOGLOBIN
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G
Primeri grupisanih familija gena
grupa gena za globine na hromozomu 16p
A
grupa gena za globine na hromozomu 11p
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rodjenje
jetraslezina Koštana sržŽumancetna kesa
adultembrion
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GEN ZA GLOBIN – deo prvog egzona
3’ – CAC GTG GAC TGA GGA CTC CTC TTC – 5’
5’ – GTG CAC CTG ACT CCT GAG GAG AAG – 3’
5’ – GUG CAC CUG ACU CCU GAG GAG AAG – 3’
val - his - leu - thr - pro - glu - glu - lys
1 2 3 4 5 6 7 8
translacija
transkripcija
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3’ – CAC GTG GAC TGA GGA CTC CTC TTC – 5’
5’ – GTG CAC CTG ACT CCT GAG GAG AAG – 3’
5’ – GUG CAC CUG ACU CCU GUG GAG AAG – 3’
val - his - leu - thr - pro - val - glu - lys
translacija
1 2 3 4 5 6 7 8
transkripcija
5’ – GTG CAC CTG ACT CCT GTG GTG AAG – 3’
3’ – CAC GTG GAC TGA GGA CAC CAC TTC – 5’
TRANSVERZIJA
S
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SRPASTA ANEMIJA
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S HEMOGLOBIN
Brzo propadanje srpastih ćelija
Taloženje srpastih ćelija ometa cirkulaciju
Nakupljanje srpastih ćelija u slezini
ANEMIJA NEDOVOLJAN DOTOK KRVI
POJAČANA AKTIVNOST KOŠTANE
SRŽI
SLABOST, ZAMOR
SLAB FIZIČKI RAZVOJ
SRČANE SMETNJE UVEĆANJE I
FIBROZA SLEZINE
OŠTEĆENJA
SRCA
PLUĆA zapaljenje
MIŠIĆA reumatizam
MOZGA paraliza
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transkripciju
obradu RNK
nestabilni globin
startni kodon
frameshift
cap mesto
male delecije
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CISTIČNA FIBROZA
NORMALNO
D E L E C I J A
Ile – Ile – Phe – Gly - Val
T ATC ATC TTT GGT GTT
Ile – Ile – - - - – Gly - Val
T ATC AT- - - T GGT GTT
F508izgubljena amino kiselina fenilalanin na položaju 508
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ABO
D E L E C I J A
Leu – Val – Val – Thr - Pro
CTC GTG GTG ACC CCT T
Leu - Val – Val – Pro - Leu
CTC GTG GT- ACC CCT T
IZMENJENI OKVIR ČITANJA OD MESTA DELECIJE
“A” alel
ABO “0” alel
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TAY SACHS ALEL
NORMALNO
I N S E R C I J A
Arg - Ile – Ser – Tyr – Gly – Pro - Asp
CGT ATA TCC TAT GCC CCT GAC
Arg - Ile – Ser - Ile – Leu – Cys – Pro-Stop
CGT ATA TCT ATC CTA TGC CCC TGA
Insercija 4 nukleotida dovodi do pomeranja okvira čitanja – FRAMESHIFT MUTACIJA
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DINAMIČKE MUTACIJE
MIKROSATELITINizovi - ponovci od 2- 4
nukleotida rasuti u genomu (na različitim hromozomima)
čoveka. Broj im je promenljiv, vrlo su polimorfni.
TRINUKLEOTIDNI PONOVCI
CGG
GAA
CAG
CTG
•Oboljenja nastaju umnožavanjem – ekspanzijom broja ponovaka
•Broj ponovaka može da se menja kroz generacije
Pojava anticipacije
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Normalna replikacija
GTC GTC GTC GTC GTC5’3’
CAGCAG CAG
3’5’
1 2 3 4 5
1 2 3
![Page 61: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/61.jpg)
GTC GTC GTC GTC GTC
CAG
CAG
CAG CAG
INSERCIJA
CAG CAGCAGCAGCAG CAG
1 2 3 4 5
1 23
2
1 2 23 4 5
3’5’
5’3’
5’ 3’
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DELECIJA
GTC GTC GTC GTC GTC
GTC
CAG CAGCAGCAG CAG
CAG CAGCAG CAG
5’3’1 2 3 5 6
4
3’5’
1 2 3 65
- 4
5’ 3’
1 2 3 4
![Page 63: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/63.jpg)
5’ 3’
FRAGILNI X SINDROM
X
FRIEDREICH ATAXIA
5
HUNTINGTON HOREA
4
MIOTONIČNA DISTROFIJA
19
CGG GAA CAG CTG
egzon intronAUG UAA
gln
CGG METILACIJA
AG AKCEPTOR INTRONA
NEFUNKCIONALNI PROTEIN
IZMENJENA STABILNOST
iRNK ?
Hipotetični gen
![Page 64: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/64.jpg)
FRAGILNI X SINDROM
NORMALNE OSOBE 6-52 ponovka (mod 30)
NORMALNE OSOBE - premutacija
50 – 230 ponovaka
OBOLELE OSOBE – puna mutacija
Stotine pa i hiljade ponovaka
- nema direktnog prelaza od normalnog broja ponovaka u punu mutaciju
- premutacija mora da prodje majčinu mejozu
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FRAGILNI X SINDROM
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FRAGILNI X SINDROM
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MIOTONIČNA DISTROFIJA
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MUTACIJE KOJE POGADJAJU POSEBNE CILJEVE
SPOJEVI EGZONA I INTRONA
GT............................AG Menjaju ili sprečavaju ispravnu obradu
PROMOTOR/ POLIADENILATNI SIGNALI
Menjaju transkripciju, sprečavaju dodavanje poliadenilatnog repa
![Page 69: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/69.jpg)
Verovatnoća da DNK polimeraza u toku replikacije ugradi pogrešan
nukleotid (1/10000)
10-5
Svaki stoti pogrešni par promakne DNK polimerazi i u toku provere
10-2
Svaki hiljaditi pogrešni par promakne sistemima popravke i nakon
replikacije
10-3
Pogrešan par - mismach
Verovatnoća zamene jednog baznog para drugim po
replikaciji = 10-5 x 10-2x10-3 = 10-10
![Page 70: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/70.jpg)
AC
CC-NH2
CH
N
N
N
HC
NH
AC
CC-NH
CH
NH
N
N
HC
NH
AMINO oblik IMINO oblik
KETO oblik ENOLNI oblik
GC
CC=OH
C-NH2
N
N
N
HC
NH
GC
CC=O
C-NH2
NH
N
N
HC
NH
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NH
N
C=O
C
C-NH2
HC
HC
NH
NH
C=O
C
C-NH
HC
HC
AMINO oblik IMINO oblik
KETO oblik ENOLNI oblik
NH
NH
C=O
T
C=O
H3C-C
HC
NH
N
C=O
T
C=OH
H3C-C
HC
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AC
CC-NH
CH
NH
N
NHC
NH
NH
N
O=CC
H2N C
CH
CH
IMINO oblik
GC
CC-OH
NH2
NH
N
NHC
NH
NH
HN
O=C
T
O=C
H3C-C
HC
ENOLNI oblik
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NH
N
C=O
T
C=OH
H3C-C
HC
ENOLNI oblik
NC
C
G
C=0
C-NH2
NH
N
HC
NH
NH
NH
C=O
C
C-NH
HC
HC
IMINO oblik
AC
CC-NH2
CH
N
N
N
HC
NH
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Izračunavanje stope mutiranja
- Utvrdjivanje učestalosti novih sporadičnih slučajeva
Autozomno dominantnih
X vezanih
BOLESTI
- koje imaju jasno prepoznatljiv fenotip na rodjenju ili ubrzo nakon
- potpuna penetrabilnost
primer ahondroplazija
- 10 dece sa ahondroplazijom
- 94075 porodjaja
- 8 od 10 dece sa ahondroplazijom rodjena od zdravih roditelja
dakle 8 mutacija na 2 x 94075 (188 150)
4 X 10-5 mutacija po lokusu/generaciji
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ahondroplazija
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spontana stopa mutiranja
Prosek za pojedinačne gene čoveka
10-4-10-6 lokus/generaciji
1 mutacija na 100 000 – 1 000 000 gameta po lokusu po generaciji
n
2N
n broj aficiranih sa neaficiranim roditeljima
N ukupan broj rodjenih beba x2 (po 2 alela)
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PRIMERI STOPE MUTIRANJA ZA ODREDJENE GENE ČOVEKA
AHONDROPLAZIJA
DMD
HEMOFILIJA A
NEUROFIBROMATOZIS – NF1
PKD
RETINOBLASTOM
0.6 – 1.4 X 10 -5
3.5 – 10.5 X 10 -5
3.2 – 5.7 X 10 -5
4 – 10 X 10 -5
6.5 – 12 X 10 -5
5 – 12 X 10 -6
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MUTAGENI
HEMIJSKI
Alkilirajući agensi, analozi nukleinskih kiselina, azotna jedinjenja
FIZIČKI
UV i jonizujuće zračenje
virusi
GENETSKI ČINIOCI
Sindromi sa naslednom nestabilnošću hromozoma : Fankonijeva anemija, Bloom-ov sindrom, Xeroderma pigmentosum
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HEMIJSKI MUTAGENI
Reaguju sa DNK i transformišu baze
Mogu da budu analozi baza – pa se tokom replikacije uključuju umesto uobičajenih baza
Ugradjuju se u molekul DNK izmedju baza (interkaliraju)
1.
2.
3.
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1. AZOTASTA KISELINA (HNO2)
HIDROKSILAMIN (NH2OH)
ALKILIRAJUĆA SREDSTVA (iperit, etilen oksid, etiletan sulfonat – EES,
etilmetan sulfonat – EMS)
2. 5 – BROMOURACIL (analog timina)
2 – AMINO PURIN (analog adenina)
3. PROFLAVIN
AKRIDIN ORANŽ
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N NH
CHNO2
O
A
N H
H
A
ADENIN HIPOKSANTIN CITOZIN
A-T G-C
![Page 83: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/83.jpg)
C=O
NH
GEMS
G
C-O-CH2-CH3
NH
GUANIN ETILGUANINNH
NH
C=O
T
C=O
H3C-C
HC
TIMIN
G-C A-T
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NH
N
C=O
C
C-NH2
HC
HC
G-C A-T
CITOZIN
HIDROKSILAMIN
NH2OH
NH
N
C=O
C
C-N-OH
HC
HC
N H
H
A
ADENINIzmenjeni
CITOZIN
![Page 85: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/85.jpg)
NH
N
C=O
C-NH2
HC
HCC
NH
N
C=O
C-NH2
H3C
HCC
NH
NH
C=O
C=O
HC
HCU
deaminacija
deaminacija
citozin
5 - metil citozin
NH
C=OHCT
H3C
C=O
NH
HOT SPOT
![Page 86: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/86.jpg)
AGCT
TCGA
AGCT
TUGA
AGCT
T GA
AGCT
TCGA
*
deaminacija
U DNK – URACIL GLIKOZIDAZA
REPLIKACIJA
AGCT
TCGA
AACT
TUGA
AACT
TTGATRANZICIJA
![Page 87: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/87.jpg)
AGCT
TCGA
AGCT
TTGA
AGCT
TCGA
AACT
TTGA
deaminacijaREPLIKACIJA
Metilisani citozin
*
TRANZICIJA
![Page 88: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/88.jpg)
NH
NH
C=O
C=O
BrC
HCU
NH
N
C=O
C-OH
BrC
HCU
C
CC-NH2
CH
N
N
N
HC
NH
A
5-BROMOURACIL (keto)
5-BROMOURACIL (enol)
GC
CC=O
C-NH2
NH
N
N
HC
NH
![Page 89: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/89.jpg)
A - T
G - C
C - G
A - T
A - T
G - C
C - G
A - T
A - T
G - C
C - G
A-Bu
A - T
G - C
C - G
A - T
A - T
G - C
C - G
G-Bu
A - T
G - C
C - G
G - C
A - T
G - C
C - G
A-Bu
Replikacija I
Replikacija II
Replikacija III
A-T G-C
![Page 90: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/90.jpg)
UGRADJIVANJE AKRIDINA U DNK
A ---- T
G ---- C
T ---- A
C ---- G
A ---- T
G ---- C
T ---- A
C ---- G
AKRIDIN
- greške tokom replikacije
- mogu da dovedu do nepravilnog crossing- overa
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BLOOM SINDROM
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Fizički mutageni 1. JONIZUJUĆE ZRAČENJE
-ELEKTROMAGNETNI TALASI
X – i - zraci
-KORPUSKULARNO ZRAČENJE
elektroni, protoni, pozitroni, neutroni
Jonizacija molekula reaktivni joni i radikali oštećenja
- greške u replikaciji
- supstitucije
- skeleta DNK
Broj štetnih mutacija zavisi od:
- vrste jonizujućeg zračenja
- primenjene doze
- vremena izlaganja zračenju (akutna i hronična doza)
![Page 94: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/94.jpg)
2. ULTRALJUBIČASTO ZRAČENJE (UV)
- mala prodorna moć
- oštećenja u površinskim ćelijama kože
C A A T G A C T--T C T A
G T--T A C T G A A G A T
NH
HN
O=C
T
C=O
C-CH3
CHNH
HN
O=C
T
C=O
C-CH3
CH
NH
HN
O=C
T
C=O CH3
C
C
NH
NH
C=O
T
C=OH3C
C
C
H H
UV
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XERODERMA PIGMENTOSUM
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NH
N
C=OC
C-NH2
HC
HC
NH
N
C=OC
C-NH2
C
Chidratacija
H
H
H
HO
DNK
UV
![Page 97: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/97.jpg)
TALASNA DUŽINA (cm) TIPOVI ZRAČENJA104
103
102
10-1 (1mm)
101
100 (1cm)
10-2
10-3
10-4 (1
10-5
10-6
10-7 (1m)
10-8
10-9
10-10
RADIO TALASI
INFRACRVENI
VIDLJIVA SVETLOST
UV
10-11
X-ZRACI
GAMA ZRACI
KOSMIČKO ZRAČENJE
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30 cGy 0.3 Gy prosečna doza za životni vek
4-5 Gy letalna400-500 cGy
0.001-0.1 Gy
u dijagnostičke svrhe0.1-10 cGy
0.1 Gy u terapijske svrhe10 cGy
1 Gy izaziva radijacionu bolest100 cGy
0.3 Gy30 cGy Udvostručuje spontanu stopu mutiranja
1 Gray = 1Gy
Rentgen ili rad = r1r = 1cGy
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Obeležavanje mutacija
•c. G1444>A
g. IVS33+2T>A
g. IVS33-2A>T
1524 – 1527 del
c. 1277 – 1278 ins TATC
Glu 6 Val ili E 6 V Gln 39 X ili Q 39 X
![Page 101: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/101.jpg)
brojperiod
ćelija deoba
5 meseci embrion
rodjenje
6.8x106 =22
2.6x106
seksualna zrelost
mejoza 2
Ukupno 24
oplodjenje
mejoza I
mejoza II
zigot
II polocita
Primordijalna geminativna ćelija
![Page 102: mutacije](https://reader033.vdocuments.site/reader033/viewer/2022061109/545169e4b1af9f6b1a8b4bda/html5/thumbnails/102.jpg)