CHNG II: GEN, GENOMICS V NHIM SC TH

Cu hi tun trc: S methyl ha, acetyl ha nh

hng n s ng/m cu trc NST nh th no?hng n s ng/m cu trc NST nh th no?

Histone modifications

4

http://www.nature.com/scitable/learning-path/chromatin-in-eukaryotic-regulation-795216

4. Cc yu t di truyn chuyn v- Yu t di truyn chuyn v trong h gen t bo nhn s- Yu t di truyn chuyn v trong h gen t bo nhn thc

5. Cc ADN ca c quan t

NI DUNG CHNG II(tip theo)

5. Cc ADN ca c quan t- ADN ty th- ADN lc lp

6. H gen hc (genomics)- H gen hc cu trc (Structural genomics)- H gen hc chc nng (Functional genomics)- H gen hc so snh (Comperative genomics)

YU T DI TRUYN CHUYN V

- L nhng ADN lp li nm ri rc trong h gen, c khnng di chuyn sang cc vng khc nhau trong h gen (cdng t di chuyn c, c dng khng t di chuyn cm cn thm yu t b tr).- Kch thc dao ng t vi trm bp n vi nghn bp.- Kch thc dao ng t vi trm bp n vi nghn bp.- Chia ra 2 dng: da trn cch thc nhn ln v chn vo hgen, bao gm

ADN transposon retrotransposon (thng qua ARN)

- sinh vt nhn s: ch yu l ADN transposon

- sinh vt nhn thc: ch yu l retrotransposon, tuynhin vn c ADN transposon

YU T DI TRUYN CHUYN V

- C 2 dng chnh: n gin nht l IS element (Insertion sequence) Transposon Tn

IS element c cu trc bao gm: gen m ha cho transposasegip cho vic chuyn v, on trnh t lp li o chiu. Trnh tch ngoi cng l trnh t lp cng chiu.

YU T DI TRUYN CHUYN V PROKARYOTE

- Ngoi cc IS element, vi khun cn c cc on ADN c khnng di chuyn vi kch thc di hn, k hiu l transposon Tn.Cc Tn thng c gii hn hai u bi cng mt loi IS.

- Cc Tn thng mang thng tin di truyn m ha cho cc proteinkhng khng sinh.

- V d: transposon Tn3, transposon Tn9, transposon Tn10

Cu trc ca transposon Tn9

C ch dichuynca IS ca IS element

- sinh vt nhn thc: ch yu l retrotransposon, tuy nhin vnc ADN transposon-ADN transposon c tm thy ng qua nghin cu ca BarbaraMcClinclock vo nhng nm 1940s, bao gm yu t phn tn Ds(dissociation elements) v yu t hot ha Ac (activator element),gy hin tng m mu ht ng.

YU T DI TRUYN CHUYN V EUKARYOTE

gy hin tng m mu ht ng.Ac - Activator element - ging nh IS element vi khun, c manggen m ha cho transposase, c kh nng t di chuynDs - Dissociative element - ging nh Ac element nhng thiu genm ha cho transposase, do khng th t di chuyn m phi phthuc vo Ac element.

-Retrotransposon bao gm: LTR retrotransposon (long terminal repeat)Non-LTR retrotransposon:

LINEs (Long Interspersed Elements)SINEs (Short Interspersed Elements)

YU T DI TRUYN CHUYN V EUKARYOTE

SINEs (Short Interspersed Elements)

LTR retrotransposon (long terminal repeat)- LTR retrotransposon ph bin nm men (v d: Ty elements) v rui gim (v d: copia elements. ngi, LTR retrotransposonchim khong 4% ADN h gen.

Cu trc ca LTR retrotransposon

C ch di chuyn ca LTR retrotransposon:- on ADN ca LTR retrotransposon khng b ct v chn vo

v tr ch m c phin m thnh bn sao ARN.- Phn t ARN c phin m ngc to ra ADN nh s xc tc

ca reverse transcriptase.- Bn sao ADN c ct v chn vo v tr ch trn h gen nh

s xc tc ca integrase (ging vi qu trnh ct v chn cs xc tc ca integrase (ging vi qu trnh ct v chn cxc tc bi transposase).

- LTR retrotransposon cha gen m ha cho reverse transcriptaseand integrase.

C ch copy-and-paste

Bng chng bng thc nghim chng t qu trnh chuyn v caLTR retrotransposon thng qua bn sao ARN. Th nghim s dngLTR retrotransposon nm men, l Ty element.

Non-LTR retrotransposon:

ng vt c v, dng retrosposon khng cha vng LTR l phbin hn (Non-LTR retrotransposon).

Non-LTR retrotransposon c hai dng chnh l: LINEs (Long Interspersed Element) SINEs (Short Interspersed Element) SINEs (Short Interspersed Element)

ngi, LINEs c kch thc khong 6 kb, SINEs c kch thckhong 300 bp.

S chuyn v ca Non-LTR retrotransposon: thng qua bn saoARN

LINEs (Long Interspersed Element)- ngi c 3 h chnh gm: L1, L2 v L3.- LINEs xut hin khong 900,000 v tr khc nhau trn h gen,

chim khong 21% h gen ngi. - Cu trc ca LINE: ORF1 1 kb, ORF2 4 kb. ORF 1 m ha

cho protein lin kt vi ARN, ORF2 m ha cho enzyme reverse transcriptase v ADN endonuclease

C ch di chuyn ca LINEs

- LINEs ADN c phin m to thnh LINEs ARN nh enzymeARN polymerase II v c gn ui poly A .- LINEs ARN c vn chuyn ra ngoi t bo cht sinh tnghp protein ORF1 v ORF2. Protein ORF1 v ORF2 lin kt viLINEs ARN to thnh mt phc hp. Phc hp ny c vnchuyn tr li nhn.- LINEs ARN c phin m ngc to bn sao LINEs ADN vchn vo h gen.

SINEs (Short Interspersed Element)

- SINEs chim khong 13% ADN h gen ngi.- di ca SINEs bin i dao ng t 100-400 bp- SINEs khng cha gen m ha cho protein m ch cha vng trnht giu A/T u 3.- C ch chuyn v ca SINEs cng thng qua phn t trung gianARN. ARN c phin m nh ARN polymerase III.ARN. ARN c phin m nh ARN polymerase III.- Phn ln SINEs cha v tr ct duy nht ca enzyme ct gii hnAluI, nn thng c gi l Alu elements. Alu elements phn b rikhp h gen ngi, thng khng gy nh hng n s biu hinca gen vng ch do v tr chn thng vng gia cc gen, vngintron ca gen hoc vng 3-UTR.

Vai tr v ngha ca yu t di truyn chuyn v: - ng vai tr nh tc nhn gy t bin. V d: SINEs (Alusequences) v LINEs gy ra mt t l t bin nh ngi, y lnguyn nhn gy nn mt s bnh nh : bnh mu kh ngHemophilia A (Factor VIII gene) v Hemophilia B (Factor IX gene), suy gim min dch cp lin kt NST X (SCID) [gene for part of the IL-2 receptor]IL-2 receptor]- C vai tr trong tin ha: nhn p gen, nhn p exon/xo trn exon do hin tng trao icho khng tng ng ti v tr transposon S chn ca transposon vo vng iu ha hot ng gen c th tora t hp mi ca cc trnh t iu ha enhancer, qua nh hngn s biu hin ca gen.

Trao i tro khng tng ng gy nhn p gen

Trao i tro khng tng ng gy xo trn exon

ADN TY TH (mtDNA) V LC LP (cpDNA)

- ADN c cu trc dng vng, kch thc mtDNA ngi l 16 569bp, nm men 78 kb, da hu 330 kb; kch thc cpDNAkhong t 120kb-160 kb.- Mang gen m ha cho cc sn phm cn thit cho bo quan. V d:rARNs, tARNs, v tiu n v ca phc hp vn chuyn in t- ADN khng tun theo quy lut di truyn ca Mendel, m tun theo- ADN khng tun theo quy lut di truyn ca Mendel, m tun theoquy lut di truyn theo dng m.- M di truyn ty th c s sai khc vi m di truyn trong nhn.V d: UGA l stop condon, ty th ngi UGA m ha chotryptophan. AGA, AGG m ha cho arginine, nhng ty th ngvt c v th chng li l stop codon, ty th rui gim chng mha cho serine.- S lng ADN ty th v ADN lc lp c th t n hng nghnbn sao trong mt t bo.

Ty th v lc lp l kt qu qu trnh ni cng sinh

t bin xy ra ADN ty th gy bnh him ngho ngi

- Hn 200 t bin ADN ty th gy bnh c xc nh, bao gmcc bnh lit c (myopathy), lit no (encephalomyopathy), hichng d dy rut (gastrointestinal syndromes), bnh lit c tim(cardiomyopathy), i ng, m, ic, bnh Alzheimer, bnhParkinson v bnh ung th.

-c im quan trng v c th trong di truyn ty th l hin tng-c im quan trng v c th trong di truyn ty th l hin tngkhng ng nht (heteroplasmy) v ng nht (homoplasmy) caADN ty th.

ADN ty th c coi l ng nht khi tt c bn sao cagenome ty th l nh nhau. ADN ty th c coi l khng ng nht khi c hai hoc nhiugenotype ty th.

t bin xy ra ADN ty th gy bnh him ngho ngi

- Trong trng hp khng ng nht ADN ty th, mc ngng tbin c gi tr quan trng i vi s biu hin lm sng v c nhngbiu hin ha sinh ca bnh. V vy, xc nh c mc khngng nht ca t bin ADN ty th c ngha cao trong chn onbnh ty th.

Phng php chuyn gen vo lc lp

-u im: gen lc lp di truyntheo dng m nn trnh c spht tn gen, s lng h gen lc lp ln nn gip gen nghincu c biu hin mc caocao

- Thnh cng: to ra cy khngsu, khng thuc dit c, snxut dc liu v vaccine thcvt

H GEN HC (GENOMICS)

- H gen hc cu trc (Structural genomics)- H gen hc chc nng (Functional genomics)- H gen hc so snh (Comperative genomics)- H gen hc so snh (Comperative genomics)

-Ngn hng gen: The GenBank, National Institute of Health, Maryland The EMBL Sequence Data Base, European Molecular Biology Laboratory, Germany

H GEN HC (GENOMICS)

- Lm th no bit chc nng ca mt gen?

-BLAST (basic local alignment search tool)

- Phng phpcho php phntch s biuhin ca hngnghn gen cng mt lc

DNA MICROARRAY

cng mt lc