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  • 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