t bin genMc tiu :- Trnh by c nguyn nhn v hu qu ca t bin.- Trnh by c cch t bo sa cha ADN h hng trnh t bin.- Nhn din c mt s bnh di truyn ngi do t bin gy ra.- Trnh by c tc ng ca cc yu t gy t bin.- M t c vic s dng cc yu t gy t bin trong phng th nghim v cc phng php chn lc t bin vi sinh vt.

M u t bin gen: S thay i trong trnh t nucleotid trn gen.

- To ra mt protein t bin vi trnh t acid amin thay i ;- Tc ng n qu trnh iu khin s tng hp ca cc sn phm gen.

Cc loi t bin gent bin sinh dng : t bin xy ra cc t bo khng sinh sn - To ra cc thay i c tnh cc b, khng di truyn c (u sc t ngoi da ngi, to ra nt rui); Nguyn nhn gy ra ung th; Nguyn nhn ca s lo ha.

t bin dng mm : t bin xy ra trong giao t , c truyn cho i sau.

t bin gen (t bin dng mm)Hu ht l t bin ln (s khng c pht hin nu hp t khng c hai bn ca allel t bin).

Pht hin v o tn s t bin cn phi quan st : Cc t bin tri ang xy ra trn nhim sc th thng; Cc t bin ln v tri trn nhim sc th X.

T l t bin ca cc gen: C hai gii thch cho s khc nhau v t l t bin ca cc gen: Kch thc ch im nng

Kch thc ch: Gen c vng m ha protein rt ln, c nhiu base c th b thay i hoc lm mt chc nng ca gen.

Th d:- Bnh u x thn kinh (Neurofibromatosis NF): do di truyn gen tri trn nhim sc th thng (l mtbnh di truynlin quan n ri lon thn kinh nh hng n no, ty sng, dy thn kinh v da. ) Bnh lon dng c Duchenne: t bin trong gen DMD; di truyn ln lin kt vi X; Gen DMD quy nh protein dystrophin protein m bo tnh ton vn ca si c. Nhng b trai vi bnh teo c Duchenne khng sn sinh protein dystrophin trong c bp ca chng. Bnh lon dng c Duchenne chim t l khong 1 trong 3500 ca sinh b trai trn ton th gii.

T l t bin ca cc gen: im nng: mt s gen nm trong vng nhim sc th nhy cm hn vi s ph hy/ thay i di truyn, hoc gen c cha cc trnh t d b thay i bi cc t bin t pht hn. V d gen chng lon sn sn c cha im nng (trnh t CpG).

Tn s t bin Tn s t bin c nh gi trn mt ln sao chp, mt ln phn bo hay trn mt giao t v trn mt t bo trong mt th h.Cc gen khc nhau ca cng mt sinh vt c th c tn s t bin khc nhau nhng tn s t bin t nhin i vi mi gen l n nh.Tn s t bin thng c biu hin: 10-nth d:E. coli nhy cm vi streptomycin t bin thnh khng streptomycin vi tn s 4.10-10 = trong 10 t t bo ca mt th h c 4 t bin StrR xut hin ngu nhin.

ngha ca t bin gen BG c ngha quan trng trong tin ha; Hu ht cc t bin l ln v nh vy s khng c biu hin trong iu kin d hp t; S thay i cc base c th xy ra trong vng khng m ha ca phn t ADN v cc acid amin b thay i c th khng lm thay i c tnh protein; thay i trnh t nucleotid c th khng biu hin thnh s khc bit tnh trng nhng l cc t bin ln tch t trong b gen. Hu ht cc t bin l bt li c th gim thiu cc bin i trong chui ADN hoc phc hi trnh t gc bng cch sa cha cc t bin.

ng dng ca t bin genK thut cm ng t bin: + Trong cy trng v vt nui to ra cc chng mi + Trong cng ngh vi sinh hc hin i to ra cc chng vi sinh vt lm tng nng sut v to ra sn phm mi.

- K thut ti t hp ADN cho php chn mt t bin c hiu vo mt gen qui dnh trc (t bin im nh hng) c th to ra cc t bin tt v hu ch.

Cc loi t bin

Cc loi t bin thng gp:t bin im t bin lch khungt bin a im

*

t bin im

t bin im : thay i mt base trong chui ADN do ha cht hoc sai st trong sao chp ADN. C hai dng t bin im chnh trong phn t DNA:t bin thay th cp base (base substitution)t bin thm bt cp base (base insertion - base delection)

*

t bin im do thay th cp nucleotid

Mt cp nucleotide trong gen c thay th bng mt cp nucleotide khct bin thay th cp base c chia lm 2 loi:

Chuyn v: Ph bin nht S chuyn v, bt cp sai, c th gy bi acid nitr hoc cc ng ng base nh 5-bromo-2-deoxyuridin (BrdU). o chuyn

*

Chuyn vT C hoc CT purine bi purine khc A G hoc G APyrimidin c thay th bi pyrimidin khc*

Chuyn vPyrimidin thay th bi pyrimidin khc T C hoc CT purine bi purine khc A G hoc G A*

Nguyn thyt binLn sao chp tipATACAT + CGGCGTGC + TACGTGTA + GCTACACG + AT

Nguyn thyt binLn sao chp tipATGTGC + TAGCACAT + CG CG CACG + ATTA TGTA + GC

t bin li bint bin im c khuynh hng c trng l t bin li (hi bin): ngha l chuyn li dng nguyn thy. iu ny xy ra v ln t bin tip theo ti cng mt im c mt phn ba c hi quay li chui ban u.*

o chuyn pyrimidin c thay th bi purine hay purin bi pyrimidin (C/T A/G). *

Cc loi t bin im t bin ln hay cn gi l t bin cng ngha: m ha cho cng acid amin, khng c nh hng n protein cui.

t bin lch ngha: m ha cho acid amin khc, c th lm protein khng c chc nng.

t bin v ngha: m ha cho codon kt thc, c th lm ct protein.

Cc loi t bin im*

UAC

Tyrosine

UAG

UAU

cung Tyrosine

CAC

Histidine

Protein la

Protein khong c

tong hp

Protein bnh thng

Lech ngha

Cung ngha

nh hng ca t bin thay th baset bin thay th base c th xy ra: trong promoter ;cc vng iu ha 5 ca gen hoc ;trong intron

t bin thay th base c th nh hng n s phin m, dch m hoc mc xon bn ca ADN. Nhiu -thalassemia l hu qu ca cc t bin khng-cu-trc ny nh hng mc biu hin cc gen globin. Mc nh hng ty thuc nucleotid b thay th v v tr ca n trong ADN.

*

Ni dung ca t bin cng ngha, lch ngha v v ngha

*

t bin ln (t bin cng ngha)

B m ha cho cng acid amin, khng c nh hng n protein cui. V d codon GCA hoc GCG trong mARN u ngha l arginin (loi ny thng ng vi t bin chuyn v v tr th ba - base linh hot ca codon.*

t bin cng ngha

t bin lch nghat bin lch ngha: m ha cho acid amin khc, c th lm protein khng c chc nng. V d trong chui protein -globin gy bnh thiu mu hng cu hnh lim: *

t bin lch ngha

t bin v ngha t bin v ngha: m ha cho codon kt thc, c th lm ct protein. Tc ng ca cc t bin v ngha ty thuc protein b ct bao nhiu v mc cn cho hot ng ca protein.Thng lm mt chc nng protein v gy bnh

*

t bin v ngha

t bin lch khung

Bn cht ca t bin lch khung: do chn hoc mt mt hoc nhiu nucleotid trong vng m ha ca gen.

Hu qu: lm thay i khung c

Thay i tt c acid amin pha sau t bin v rt d to sn phm khng chc nng v khc hn vi protein bnh thng. Ngoi ra, cc khung c sai thng cha cc codon kt thc, s lm qu trnh tng hp protein dng sm.

*

Vic thm hoc bt mt nucleotid vo khung c s lm thay i acid amin k t v tr tr i.Nu t bin thm hoc bt cng xy ra trn mt phn t ADN th do trao i cho gia cc base tng ng m t bin m c th sa cha li khung c sai do t bin dng gy ra. Nh ch c acid amin no nm gia hai im t bin b sai m thi. Nh vy, t bin m tc ng nh mt t bin km hm ngoi gen i vi t bin dng hoc ngc li. *

t bin lch khung c do mt nucleotide

t bin lch khung do thm nucleotide

t bin a im Bn cht:Nhng thay i tc ng n hn mt base; Thay i t hai n hng ngn base, nhng thng nht l ch vi base.

Hu qu: thng l xo b mt phn ca trnh t m ha. t bin a im khng c tnh hi bin, ngha l t bin c n nh.

Phn bit t bin im v t bin a im v nguyn nhn v hu qu

*

t bin imt bin a imNguyn nhnThay i mt base trong chui ADN do : s chuyn v, pyrimidin c thay th bi pyrimidin khc hay purine bi purine khc (A G, C T) o chuyn pyrimidin c thay th bi purine hay purin bi pyrimidin (C/T A/G) Nhng thay i tc ng n hn mt base: Thay i t hai n hng ngn base, nhng thng nht l ch vi base

Do gen nhy hoc cc li khi sao chp ca cc yu t lp li (v d cc lp li AT)

Phn bit t bin im v t bin a im v nguyn nhn v hu qu

*

t bin imt bin a imHu qu t bin cng ngha: Khng c nh hng n protein cui t bin lch ngha: Codon mang t bin m ha cho acid amin khc , c th lm protein khng c chc nng t bin v ngha: Codon mang t bin m ha cho codon kt thc c th lm ct protein.Xo b mt phn ca trnh t m ha dn n cc hu qu: S xa mt on ln s lm thay i hon ton protein to ra, xa b on ngn cng gy hu qu nghim trng nu n lm thay i khung c (nu s lng base b xa khng chia ht cho ba).

Nguyn nhn t bin- t bin t nhin (xy ra mt cch t pht) ;- t bin cm ng gy bi cc tc nhn t bin.

t bin t nhin Xy ra trong t nhin mt cch ngu nhin ; Xy ra vi tn s nht nh; Khng xc nh c ngun gc.

C ch Do s gn sai base trong qu trnh sao chp ADN s to ra mt t bin im.T l t bin t pht l 1/107 bn m sao ca gen s c mt t bin im, ngha l 10-7 t bo s c t bin v gen .

Cc dng t bin t nhin:

- h bin, - kh amin,- lch khung, - v oxy ho ph hu do cc gc t do.

*

1. H binBn loi base ca ADN c th tn ti dng h bin, tc l kh nng hon v gia hai dng keto v enol; amino v imino. Nu trong khi ADN sao chp, G dng enol, polymerase s thm T vo thay v bnh thng l C + Nh vy G C chuyn v thnh G T+ Khi sao chp mch T, s l A - T Kt qu l s chuyn v G-C thnh A-T gy t bin chuyn v. Dng imino (=NH) him gp, nhng cng gy bt cp nhm. *

Th d 1: 5-Bu (5-Br Uracyl) c th bt cp vi Adenin to A = 5Bu (dng keto). Nhng khi 5-Bu h bin sang dng Enol (5-Bu*) th 5Bu* li bt cp vi Guanin to G 5Bu*. T mch khun, G c sao chp thnh G C, nh vy A = T chuyn thnh G C.

*

Th d 2: Guanin c th bt cp sai vi 5-Bu dng enol to: G 5Bu*. khi Bu* h bin thnh Bu.T mch khun G sao chp thnh A = Bu T mch khun A sao chp thnh A = T, nh vy: G C thnh A = T. *

2. Kh amin

Cc phn ng kh amin thng gp l cc phn ng thy phn, lm cho:Cytosin UracilCH3 Cytosin ThyminAdenin HypoxanthinS bin i ny dn n bt cp sai.

Th d: cytosin bnh thng bt cp vi Guanin to C G. nu cytosin b kh thnh Uracil th c th bt cp vi Adenin. Do :C G U = A A = T*

C G U = A A = T*

*

3. Lch khung (chn hoc mt nucleotide trn si ADN)Thng l li ca ADN polymerase khi sao chp cc on lp li ca mt nucleotide.Th d: proflavin, cam Acridin, Ethidium bromide, lm dn si i v ADN polymerase b nh la chn base vo v tr i din nhiu hn bnh thng. *

4. Oxy ha ph hy do cc gc oxy Cc gc oxy tng ln trong t bo do chuyn ha oxy ha (hay do phng x). sn phm oxy ha quan trng l 8-hydroxy Guanin, gy o chuyn G C thnh T = A. *

t bin cm ng do cc tc nhn gy BCc tc nhn gy t bin:- lm tng tn s t bin cao hn mc t nhin c th lm thay i cu trc hoc trnh t ADN l tc nhn vt l: phng x, tia X, tia t ngoi, Tc nhn ha hc: cc ng ng ca cc base nit, acid nitr (HNO2), cc cht alkyl ha mnh.

Tc nhn ha hc gy t binTc nhn gy t bin ha hc c chia lm 4 nhm :Nhm base ng ngCc cht ha hc thay i cu trc v c tnh bt cp ca cc base, gm cc cht kh amin v cc cht alkyl haNhm chn vo ADN (tc nhn lm lch khung)Cc tc nhn thay i cu trc ADN

Bn tc nhn ha hc gy t bin1. Nhm base ng ng: c cu trc ging purin hay pyrimidin c th gn vo ADN ti v tr ca cc base bnh thng khi sao chp. Th d: BU ng ng ca ThyminAminopurin ng ng ca Adenin

Cc tc nhn ny gy chuyn v nh gy h bin t pht.

*

Nhm base ng ng: bromouracil (5-Bu) v aminopurine.

BromUracil (Bu) thymin (Br thay cho CH3-Bu) nn c th bt cp vi Adenin khi Bu h bin t dng Ceto sang Enol (Bu*) c th bt cp vi Guanin to Bu*- G,

A = T c thay bng G C*

A

A

BU

Sao chp

(Mch khun A)

G

C

G

BU*

T

Sao chp

(Mch khun BU*)

(Mch khun G)

Sao chp

A

BU

Sao chp

(Mch khun G)

Bc t bin

G

C

G

BU*

A

T

Sao chp

(Mch khun BU)

(Mch khun A)

Sao chp

(b)

(a)

PAGE

1

Aminopurin ng ng ca Adenin. Aminopurin c th bt cp vi Thymin hoc Cytosin (him khi) gy chuyn v.

2. Cc cht ha hc thay i cu trc v c tnh bt cp ca cc base, gm cc cht kh amin v cc cht alkyl ha

2.1. Tc nhn kh amin: acid nitr to bi s phn gii cc nitrit (cht bo qun) trong thc phm bin : - Cytosin thnh Uracil; - Methylcytosin thnh Thymin; - Adenin thnh hypoxanthin kh amin, hypoxanthin trong ADN bt cp vi C gy chuyn v.

*

C ch kh nhm amin (NH2) ca cc base nitric gy bt cp sai:

RNH2 + HNO2 R-OH + N2 + H2O

R-OH bt cp sai

Th d cht kh amin nh acid nit (HNO2) kh:

Cytosin thnh Uracil; hoc Adenin thnh Hypoxanthin. .

*gy bt cp sai

2. 2. Tc nhn alkyl ha : Nitrosoguanidin (NTG), S) Methyl methane sulfonat (MMS), Ethyl methane sulfonat (EMS), c th gy t bin t nht bng 3 cch :Thm nhm methyl (-CH3) hay ethyl (-C2H5) vo Guanin to base ng ng ca Adenin dn n s bt cp b sung sai ;Mt purin do Guanin b alkyl ha to l hng trn ADN, khi sao chp c th lm t mch;Lin kt cho gia cc mch ca mt hoc cc phn t ADN khc nhau lm mt nucleotid.

_1190814545.bin

Tc nhn ha hc gy t bin3. Nhm chn vo ADN (tc nhn lm lch khung): cc cht proflavin, cam acridin, ethidium bromide l cc phn t a vng phng tng tc vi cc base ca ADN v chn vo gia chng. S chn ny lm gin si i ADN v ADN polymerase b nh la chn base vo i din nhiu hn bnh thng, lm lch khung ADN to thnh.

*

Tc nhn ha hc gy t bin4. Cc tc nhn thay i cu trc ADNCc tc nhn ny c th l:Cc phn t ln (knh cng) gn vo base trong ADN v lm chng tr thnh khng m ha. V d N-acetoxy-2-acetylaminofluorene (NAAAF)Cc tc nhn gy lin kt cho trong v gia cc si. V d cc psoralen c trong mt s rau v dng trong iu tr mt s bnh da.Cc cht ha hc gy t si ADN. V d cc peroxid.Cc hydrocarbon a vng. V d cc benzypyrene c trong xng.

*

Tc nhn bc x gy t binTc dng gy t bin ca bc x c 2 c im:Khng c ngng tc dng tc l khng c liu lng v hi.S lng t bin t l thun vi liu lng phng x, khng ph thuc vo cng v thi gian chiu x.

*

Cc bc x in tBc sng ca cc bc x ny thay i ty theo loi bc x v t l nghch vi nng lng ca chng.Cc sng di nht (radio AM) c nng lng t nhtcc sng ngn hn l FM, TV, viba, hng ngoi, kh kin, tia t ngoi (UV), tia X v tia gamma ln lt c nng lng gia tng. Tia t ngoi (cn gi tia cc tm) c nng lng phng x cao nn c ngha sinh hc.

*

Bc x ion haTia X, tia gama, ht phng x v c th lm ion ha cc phn t trn ng i ca chng v gy bin i ADN do c tc ng mnh n cc phn t sinh hc. Bc x UV khng ion ha nhng c th phn ng vi ADN v cc phn t sinh hc khc, v cng l tc nhn t bin quan trng: Tia t ngoi lm tng mc nng lng ca nguyn t, thng to dimer pyrimidin (gn hai thymin k nhau ca mt mch.)

*

Ngun bc xBc x t nhin sn xut bc x nn.

- Ngun bc x t nhin : + cc tia v tr t mt tri v khng gian; + t cc nguyn t hot ng phng x trong t, trn mt t v trong khng kh (radon). - Mc bc x nn thay i ty vng a l.

Tc dng sinh hc ca bc xBc x ion ha sn sinh cc gc t do;Cc gc t do s tng tc vi ADN, protein, lipid trong mng t bo, v.vc th gy h hng ADN v protein, c th lm hng c quan, ngn phn chia t bo hoc lm cht t bo.

nh hng di truyn ca bc x

1. Bc x ion ha c th gy: t mt hoc c hai si (c th dn n sp xp li, xa mt, mt nhim sc th, t bo cht nu khng sa cha). Ph hy cc base (t bin). Lin kt cho trong ADN hoc ADN vi protein.

2. Vai tr gy t bin ca tia UVBc x UV c u tin hp ph bi cc base ca ADN v cc acid amin thm ca cc protein, v th n c nh hng sinh hc v nh hng di truyn quan trng.UV c phn loi theo bc sng: - UV-C (180 - 290 nm): st trng mnh nht, gy cht, khng c trong nh sng mt tri v n c hp ph bi tng ozon.- UV-B (290-320 nm): phn on gy cht/t bin chnh ca nh sng mt tri- UV-A (320 nm - kh kin) l cn UV, cng c tc dng xa mt (v n to cc gc oxy) nhng n sn xut rt t dimer pyrimidin. *

UV-B v UV-C: to cc dimer pyrimidin trong ADN, y l lin kt ng ha tr gia cc pyrimidin k nhau trong mt si

Cc dimer ny lm ngn chn s phin m v sao chp ADN v gy cht nu khng sa cha.

Chng c th kch thch t bin cng nh sp xp li nhim sc th.

Di tc ng ca tia t ngoi, cytosin gn thm phn t nc vo lin kt C=C ca mch vng v thymin b t lin kt C=C mch vng, ni 2 phn t thnh thymin dimer.

*

Tc ng ca tia t ngoi ln cc pyrimidin(a) Dimer thymin-cytosin (b) Dimer thymin-thymin

*

PAGE

1

_1191024630.bin

Cc c ch chng li t bin o nghch sai hng: enzym hot ng phc hi cu trc bnh thng khng c gy khung. Loi b sai hng: ct b v thay th base hoc phn nucleotid sai hng hoc khng thch hp. Dung np sai hng: khng sa cha tht s, chp sai hng v tip tc sng. *

3 c ch thng gp:

Quang phc hi (photoreactivation) Lm mt nhm alkyl Ni cc ch t si ADN

o nghch sai hng

*

o nghch sai hng = quang phc hi.

Bn cht ca quang phc hi:enzym phospholyase xc tc phn ng ct cc dimer pyrimidin c to ra di tc ng ca tia UV bng cch lm t cc lin kt ng ha tr.Hin tng quang phc hi l mt c trng trong tc ng ca tia UV. Sau khi chiu tia t ngoi ln t bo, nu ngoi nh sng, th cc sai hng phn ln c phc hi. nh sng c tc ng hot ha enzym phospholyase, ct t cc thymin dimer.

*

*Enzym photolyase xc tc phn ng ny, c nhiu trong vi khun, t bo nhn tht bc thp, cn trng v thc vt, khng c trong ng vt. Gen phr c ng vt c v nhng m ha cho protein c chc nng h tr loi sa cha khc.

DNA

T

T

UV

PR

T

T

DNA vi dimer

PAGE

1

Sa sai bng cch lm mt nhm alkyl (dealkylation)

*Enzym O6-methylguanin-ADN methyltransferase chuyn nhm alkyl t nguyn t oxy trn ADN sang gc Cystein trn enzym ny lm enzym ny mt hot tnh. Phn ng khng thun nghch.Cc li c sa cha gm O6-methylguanin, O4-methylthymin, v cc methylphosphotriester gy ra bi cc tc nhn alkyl ha nh N-methyl-N-nitro-N-nitrosoguanidine (MNNG). Enzym ny cng sa cha cc guanin b alkyl ha khc nh O6-ethylguanin v O6-butyl-guanin, mc d hiu sut thp hn nhiu. Cc MTase c tm thy tt c sinh vt c nghin cu.

Th d E. coli: *Enzym O6-methylguanin-ADN methyltranferase chuyn nhm alkyl t nguyn t oxi trn ADN sang gc Cystein trn enzym.

EMBED ChemWindow.Document

Methyltransferase

C hot tnh

Bt hot

O6-Methylguanin

Guanin

PAGE

1

_1190892636.bin

Sa sai = Ni cc ch t ca si n

ADN ligase c th nhanh chng ni li cc si ADN b t do tia X hay ha cht nh peroxyd gy ra.

Chng li B = Loi b sai hng

Theo cc c ch:Ct b base sai Sa cha lch iSa cha bng ct nucleotid NER (nucleotide excision repair)

*

Loi b sai hng = Ct b base sai

Enzym N-glycosylase nhn bit cc base sai v thy gii lin kt N-glycosilic (ni base vi ng pentose) to ra v tr khng c purin hay pyrimidin (AP).

Sau , endonuclease ct b AP v ADN-polymerase chp y ch trng da vo khun mch b sung i din v c ligase ni li.

*

N-glycosylase nhn bit cc base sai v thy gii lin kt N-glycosilic to ra v tr khng c purin hay pyrimidin (AP).

Endonuclease ct b AP ADN-polymerase chp y ch trng da vo khun mch b sung i din v c ligase ni li.*

Loi b sai hng = Sa cha lch i

Mt nhm protein c th qut ADN va mi c sao chp tm cc base bt cp khng chnh xc (hoc base khng bt cp) lm sai lch hai chiu xon kp. Base khng chnh xc s c loi b v ADN polymerase s hot ng ln th hai to trnh t ng.

*

Sa cha bng h thng NER (Nucleotid Exision Repair)

H thng NER gm:Endonuclease ct si ADN cha sai hng c hai pha.Exonuclease loi b on ADN ngnADN polymerase lp nucleotid vo khong trng

*

*

DNA vi dimer

Khong trng c lp nh ADN polymerase

Dimer b loi b

Khe h c hn li nh ADN ligase

Dimer c nhn din v ADN b ct

PAGE

1

*

Chng li B = Dung np sai hng

Sa cha bng ti t hp Sa cha bng t bin*

Sa cha bng ti t hp Ti t hp tng ng: y l c ch sa cha lp khuyt si con khng dimer da vo s tng ng ca si nhim sc th em trong qu trnh trao i cho.Ti t hp khng tng ng: y l phn ng lin kt u khng tng ng sa cha u ADN b t, gy do bc x ion ha hay cht gy t bin.

*

Sa cha sai hng bng ti t hp

3

1

2

PAGE

1

*

Sa cha bng t bin ADN polymerase b ngn ti dimer lm thay i tnh c hiu ca enzym, nh n c th chn bt c nucleotid i din no vo v tip tc sao chp.

*

Sa cha sai hng bng t bin*

*Sa sai nh h thng SOS H thng sa cha ny c kch hot nu cc c ch trn b qu ti bi cc t bin lan rng.Trong trng hp ADN b tn thng ngng sao chp, th phn ng SOS hi phc sao chp v chuyn sai hng thnh sa sai trong khi nhn i.

Cc tnh trng t bin v protein t bin

Bn cht ca t bin gy hi chng Alkapton niu

t bin gen m ha cho enzym homogentisate 1,2-dioxygenase(HDG) = homogentisate oxidase.t bin hay gp nht l thay valin cho methionin v tr 368.S t bin ny gy thiu enzym homogentisate oxydase trong gan nn khng phn hy c acid homogentisic (tn c l alcapton) thnh mt sn phm khng mu l acid acetoacetic.Acid homogentisic tch t li trong nc tiu v c mu en khi gp khng kh.Bnh do gen ln, nm trn NST thng t bin

*

*Chui phn ng sinh ha ca bnh Alkapton niu v Phenylketon niu, hai s ri lon di truyn ca s thoi qu acid amin thm

CH

2

CHCOO

-

Phenylalanine

THC AN

+

NH

3

Phenyl ceton nieu

(Thieu phenylalanin hydroxydase)

CH

2

COCOOH

Phenylpyruvate

Transaminase

Phenylalanine

trong mau cao

Phenylalanine

hydroxilase

HO

CH

2

CHCOO

-

+

NH

3

CH

2

CHCOO

-

OH

HO

Tyrosine

HO

CH

2

COCOO

-

HO

CH

2

COCOO

-

OH

HO

CH

2

COO

-

OH

ALCAPTONURIA

(thieu homogentisate oxidase)

Fumarate + Acetoacetate

Chu trnh Krebs

CO

2

+ H

2

O

Homogentisate

oxidase

2,5-dihydroxi-

phenylpyruvate

4-hydroxy-

phenylpyruvate

Homogentisate

Nc tieu

t bin sinh dng vi sinh vt - Th nguyn dng c th tng hp tt c cc thnh phn t bo - VSV khuyt dng c th do mt hot tnh enzym tng hp cc phn t phc hp.

t bin v bnh ngi t bin gen v ung th c ch phn t, ung th lin quan n cc bin i di truyn trn ADN lm tn thng tin trnh tng sinh bnh thng.Cc nhm gen lin quan ti ung th - Th nht, cc bin i lm tng hot gen kch thch, kiu t bin ny c hiu qu tri. Allel bin i c gi l oncogen (gen ung th), cn allel bnh thng l proto-oncogen (gen tin ung th).Th hai, cc bin i lm bt hot gen km hm, kiu t bin ny thng c hiu qu ln. Gen km hm c gi l gen c ch khi u.

Gen ung th v gen tin ung thCc gen ung th do retrovirus ti np

Cc retrovirus bng con ung sao chp ngc tch hp c ADN ca mnh vo nhim sc th t bo ch.Chng c th ngu nhin mang cc gen ung th lm bin i t bo ch bng cch xen on ADN ca mnh cnh gen tin ung th ca t bo ch. Cc gen tin ung th hu nh lin quan n cc h thng tn hiu ca t bo nh cc protein, cc th th xuyn mng, cc gen iu ho, .

Cc cch bin i gen tin ung th thnh gen ung thBa cch ch yu : - Mt on hoc t bin im trong trnh t m ha- Khuch i gen - Cu trc nhim sc thCc gen c th b bin i do t bin im, mt on, chuyn on nhim sc th hay do xen on b gen ca retrovirus

Ba cch bin i gen tin ung th thnh gen ung th

Khuech ai gen

Cau truc lai nhiem sac the

Mat oan hay ot bien iem trnh t ma hoa

ADN

hay

ARN

Protein tang hoat c tao ra vi so lng bnh thng

Protein bnh thng c sieu san xuat

Cac enhancer manh ke can lam protein bnh thng c tang san xuat

S dung hp vi gen phien ma manh lam protein dung hp c tang san xuat hoac protein dung hp tang hoat

25. Cc h thng chn lc t bin vi sinh vtCc h thng chn lc t bin gip pht hin cc t bin him hoi trong ngun t bin rng ln. Cc h thng chn lc t bin vi sinh vt hon thin cc phng php chn lc t bin trong phng th nghim.

Phng php khng: Dng thuc hoc phage chn lc vi khun.

*

t bin khuyt dng

Phng php lm giu chm: Dung dch vi khun pha long c cy trn b mt mi trng thch ti thiu mc thnh cc khun lc ri. Ph mt lp mng mi trng tng t ln mt mi trng thch va ri, cc khun lc bnh thng mc ln. Sau li ph thm mt lp mi trng dinh dng c b sung v tip cho cht b sung khuch tn. Cc t bin khuyt dng s mc sau khi c cht b sung, nn khun lc nh hn do mc chm. *

Phng php lm giu hn ch Cc vi khun c cy trn mi trng ti thiu c mt t cht b sung. Trong iu kin ny, cc t bin khuyt dng mc n khi ht cht b sung th dng, do to khun lc nh. Cc vi khun bnh thng tip tc to khun lc to.

*

Phng php lm giu nh penicillin Penicillin c tc ng dit khun dng phn chia. Vi khun c cho vo mi trng ti thiu c penicillin. Cc vi khun ang tng trng b dit, ch cc t bo t bin khng tng trng cn sng st. Sau , hn hp c cy ln mi trng khng c penicllin th cc t bin mc ln vi t l tng i cao hn.

*

Phng php lcDng chn la cc t bin khuyt dng nm si. Dung dch bo t c nui trong mi trng dinh dng thiu cht b sung. Cc t bin thiu cht b sung khng mc c, cc dng bnh thng mc ra thnh nhiu si. Khi lc qua mng lc si thy tinh, cc dng bnh thng nhiu si b gi li, cc dng t bin i qua mng lc. Dung dch c nhiu dng t bin c cy trn mi trng c cht b sung v kim tra tm cc dng t bin.

*

Phng php in (a) a gc trn mi trng y .

(b) Khc g bc ming nhung.

(c) Mi trng c b sung cht A v B. (d) Mi trng c b sung cht A, B v C. (e) Mi trng c b sung cht A v C*

(e)

Cac ban sao tren moi trng co bo sung

Mieng nnhung

Khuc go

a goc tren moi trng ay u

(c)

(d)

(a)

(b)

*