CURS 1 Genetica MD Feb 2016
Transcript of CURS 1 Genetica MD Feb 2016
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CURS
1 – 29 februarie 2016
GENETICA - MEDICIN! DENTAR !
AUTOR:PROF.DR. EMILIA SEVERIN
UMF Carol Davila
Bucure!ti
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ER
EDITATE
VAR I
ABILI
TATE
CURS 1 - A nu se copia sau distribui fara copyrightGENETICA MD
!
GENETICATermen derivat din lb.greac": GENETIKOS = origine, genez"
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Este un PROCES INFORMATIONAL.
Define#te însu$irea unui individ de a transmite la descenden%icaracterele speciei c"reia îi apar%ine, precum $i o parte dintre
caracterele personale.
EREDITATEA
CURS 1 - A nu se copia sau distribui fara copyrightGENETICA MD
#
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GENOTIP - FENOTIP
!"#$#%!'()(*()+,-
./'.+0 12 '%23#45"6 !.7'(
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INFORMA&IA GENETICA :INSTRUCTIUNI CARE DETERMINA CUM VA AR !TA ORGANISMUL 'I CUM VA FUNC&IONA.
('8+-7.)
$
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GENETICA MD
9 ::; <=$>?
2?@">?A" 2" 3"#$#"
CURS 1 - A nu se copia sau distribui f "r " copyright
%
ORGANISMUL UMAN
BC 2" 3>DEDFDE? GH
3"#$#"#" IDE%<3" 9 :JK;;; L"H"
M6: N O;P =KH
+,-
(>L%H?IE
=#$>?3"#$#%>
celul!
Nucleu
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De la GENE.. . la FENOTIP
&
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EREDITATE
ADN
EXPRIMARE TRANSMITERE
!(,(-
Q'+-.!'7RQ71 +'-
Q'+-.S+Q71 R'(Q17-+
'1RS7!+'1
,?T?F?$H" 3"#$#%>%
STOCARE
INFORMATIA GENETICA
CURS 1 - A nu se copia sau distribui fara copyrightGENETICA MD
'
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GENETICA MD CURS 1 - A nu se copia sau distribui f "r " copyright
(
ARBORELEGENEALOGIC al
FAMILIEIREGALE DINMAREA
BRITANIE
MESAJUL GENETIC SE TRANSMITE IN SUCCESIUNEA GENERA&IILORFAMILIA REGALA DIN MAREA BRITANIE
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Defini(ie:
VARIABILITATEA
ansamblul fenomenelor care
p r o d u c D I F E R E N ! ELEGENETICE dintre indiviziiunei popula(ii.
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)
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FIECARE INDIVIDARE o STRUCTURA GENETICA UNICA #i CARACTERISTICA
La nivel molecular, secventele deADN au o identitate de
99,9% intre indivizii umani.
Identitatea genetica UNICAse datoreaza diferentelor
de 0,1% a secventelor ADNcare produc diferentelegenetice dintre indivizi.
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*+
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VARIABILITATE
)17(*+
'"3DEU?H%>"?HA>%3>DEDFDE?%#%
'"3DEU?H%>"?HA">3>DEDFDE?%#%
V1!/-,+Q71
'"3DEU?H%>"L"HDE?3%
8"H?3"
!>DEDFDE?%#"
8"HDE?3"
)?AD3DH2>?%#"
MIGRA&IA MUTA&IA
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**
RECOMBINAREAGENETICA
MECANISMELE VARIABILIT!&
II GENETICE
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CUM SE POT PRODUCETULBUR !RILE DE ORIGINE GENETIC! ?
ADN ARN PROTEINA
FENOTIP(tr"s"tura,caracter)
MUTA&IE
MODIFICARI ALESECVENTEI ADN,ANOMALII
CROMOZOMIALE
MODIFICARI ALEEXPRESIEI GENICE,SINTEZA UNORMOLECULE ARN
ANORMALE
MODIFICARI ALEACTIVITATIIENZIMATICE,DEFECTE DE
STRUCTURA ALECELULELOR SAU&ESUTURILOR
MODIFICARI ALESTRUCTURII SI
FUNCTIEI UNUIORGAN, ERORIINNASCUTE DEMETABOLISM,DEFECTE DEDEZVOLTARE
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*#GENETICA MD
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CELULA
EUCARIOTA vs. PROCARIOTA
!1S/S+
1/!+'7(Q+
!1S/S+
R'(!+'7(Q+
-/!S1(7,-/!S1(S
-/!S1/
'7W(*()7
)7Q(!(-,'71
)1)W'+-+ !1S/S+'+
VS+81S
!+R./S+
R1'1Q1 !1S/S+'
CURS 1 - A nu se copia sau distribui fara copyrightGENETICA MD*$
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CROMOZOMI – GENE - ADN
15GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright*%
CROMOZOM
ADNGENA
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CARTI
PROPOZITII
S7Q1'1
!'()(*()7
81-1
+,-
NIVELE DE ANALIZA GENETICA
GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright*&
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5METABOLOMICA – studiul tuturor metabolitilorcare iau parte la un proces biologice.
GENOMICA – studiul structurii, organizarii sifunctiei genomului uman.
4INTERACTOMICA – studiaz" interactiunilecomplexe dintre genom, transcriptom si proteom.
3PROTEOMICA – studiul functiei unor structuri pebaza expresiei globale a proteinelor.
2
1
IERARHIA SPATIILOR “OMICE”
TRANSCRIPTOMICA - studiaz" profilul expresieigenice.
FENOMICA – studiul tuturor fenotipurilorexprimate de o celula, tesut, organ, organism.6
GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright*'
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GENETICA #i GENOMICAtermeni similari sau distinc(i?
GENETICA GENOMICA
un hibrid rezultat din casatoria
biologiei molecularecu genetica clas ica s i adoptat de sti intacomputationala ).
GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright
Principala diferen(a dintre GENETICA si GENOMICA:
Genetica studiaz" structura si functia unei singure gene in timp ce genomica studiazatoate genele si interrelatiile dintre ele cu scopul de a identifica influenta lor
combinata asupra cresterii si dezvoltarii organismului.
*(
Studiul eredit"(ii sivariabilit"(ii.
Domeniul geneticii
care se ocup" custructura #i func(iagenomului .
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GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright
MEDICINA GENOMIC!
X studiaz" func%iile $iinterac%iunile tuturor genelordin genom $i interac%iunilegenomului cu mediu asupra
fenotipului normal $i patologic, în starea de s"n"tate $i boal"
pentru to(i indivizii.
X va fi o medicin" individualizat" care va schimba cu certitudinepractica medicinii, furnizând
îngrijiri medicale adaptate lanecesit"%ile individului.
*)
,-./0/12 3-14,/05
P4 – medicina predictiv",preventiv", personalizat" $i
participativ".
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CE TEME SE VOR STUDIALA CURSUL DE GENETICA MD ?
STRUCTURA ADN
FUNC!IILE ADN
GENACROMOZOM
GENOM(nuclear si mitocondrial)
FENOTIP(caractere umane)
7E%L?H" =>"#$3>%A%./'.+0 YZ=0[[H"\IKUU3K3DK$][Y?["HL#?IY[IA%<3[?H^2"=AY[I3?^A"3Y[:;;;[Y$E%H^L"HDE"[2"@%$#AKIAE
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CAPITOLUL 1
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BAZELE MOLECULARE ALE EREDIT!)II
!*
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NATURA MATERIALULUI EREDITAR
Unde este
stocat" informa%iagenetic"
încelula Ek ?
Ce component
nucleararerolul
important inereditate ?
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1.Unde este stocat" informa%ia genetic" în celula Ek ?
Experimentullui
HAMMERLING
La Ek informa(ia genetic" estestocat" în nucleu.
Folose"te algamonocelular!
marin! ACETABULARIA.
Demonstreaz! rolul nucleului în
activitateacelular!.
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'"L?$H"
U%F%#%
Acetabulariacrenulata Acetabulariamediterranea 7HA">I3Y?EU H$3#"%>
-$3#"$
-$3#"$# >"L"H">"%F%
=_#_>?%
GENETICA MD
!$
Experimentul lui J.HAMMERLING
-$3#"$
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ROLUL NUCLEULUI ÎN DETERMINISMULCARACTERELOR FENOTIPICE
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CONCLUZIE
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6789 :;<= >;9;
?
!"#$% '( )** +(,- './'0 ?
!"#$% '( )** +(,- './'0
Celulele stocheaz" informa(iagenetic" în nucleu.
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2. Ce component nuclear are rol în
EREDITATE ?
! ACIZII NUCLEICI ! PROTEINELE .+/
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DEZBATERE 'TIIN&IFIC! INTERNA&IONAL!
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!'
DOVEZI experimentale ale
ROLULUI ADN în EREDITATE
*)!( *)$$ *)%!
EXPERIMENTUL
LUI
GRIFFITH
EXPERIMENTUL
LUIAVERY
EXPERIMENTULLUI
HERSHEY&CHASE
EXPERIMENT
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EXPERIMENT
F.GRIFFITH, 1928
Se utilizeaz":
Dou! tulpinidiferite de
pneumococi careproduc pneumonie:
#oareci pentrutestarea
patogenit!$iibacteriilor.
Pneumococitip S
capsulati,patogeni
Pneumococitip R
necapsulati,nepatogeni
SCOPUL EXPERIMENTULUI:
Cum se poate ob(ine un vaccinimpotriva pneumoniei
bacteriene?
GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright!(
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GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright
!)
STREPTOCOCCUS PNEUMONIAE
COLONII de tip R COLONII de tip S
Tipul R este benign,lipsit de o capsula
protectiv" este atacatde sistemul imun al
gazdei.
Tipul S este virulent,cu o capsula protectiv" este dificil de detectat
de sistemul imun algazdei.
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TRANSFORMAREA BACTERIANA Diplococcus (streptococcus) pneumoniae
Experiment de CONTROL
Tipul R (rough): Bacterii necapsulate,nevirulente, colonii cu aspect rugos
Tipul S (smooth): bacterii capsulate,Virulente, colonii cu aspect neted
Tipul S omorat prin incalzire
Amestec tip Rsi tip S omorat
prin caldura
Izolare de bacteriitip S vii,virulente
IN VIVO
Experimentul lui GRIFFITH, (1928)
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EXPERIMENT
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EXPERIMENT
AVERY, MacLEOD si McCARTY, 1944
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ADN este materialul genetic ?
Experimentul in vitro utilizeaz" ADN izolat de la otulpina de pneumococi S capsulati, patogeni,
#i pneumococi R necapsulati, nepatogeni în cultur".
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Celula bacteriana este descompusain componentele
esentiale
ARN proteinaADN
TESTAREA CAPACIT!&II de TRANSFORMARE a diferitelor tipuri de molecule
lipid carbohidrat
Bacterii tip R Bacterii tip R Bacterii tip S Bacterii tip R Bacterii tip R
EXPERIMENTIN VITRO
Colonie bacteriana S
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Pneumococi tip S
EXPERIMENT
AVERY, MacLEOD si McCARTY, 1944
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CLARIFICA “PRINCIPIULTRANSFORMARII”
GENETICE:
ADN
este “agentultransformator ” #i are
capacitate detransformare
genetic".
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ADNeste material
genetic.
EXPERIMENT
AVERY, MacLEOD si McCARTY, 1944
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#%
TRANSFORMAREA GENETICA
TRANSFORMAREAGENETIC!
Transform"rilesunt
SPECIFICE,
DEFINITIVE
"i EREDITARE.
DEFINI&IE:Transferulinforma(iei
genetice cuajutorul ADN.
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EXPERIMENT
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GENETICA MD
#'
EXPERIMENT
HERSHEY #i CHASE, 1952
BACTERIOFAGUL T2 "i celula gazd! E.coli
ADN
Capsida înveli# proteic
CAP
Cro#etede fixare
CURS 1 - A nu se copia sau distribui fara copyright
EXPERIMENT
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ADN viral marcat cu 32P Capsida viral" marcata cu 35S
CURS 1 - A nu se copia sau distribui fara copyrightGENETICA MD#(
CAP
COADA
•
infectarea celulelor gazd" E.coli cu bacteriofagi marca(i diferit:
ADN viralneradioactiv,
nemarcat
ADN viralradioactiv,
marcat cu32P
EXPERIMENT
HERSHEY #i CHASE, 1952
Proteina viral" radioactiv",marcat" cu
35SProteina viral"
neradioactiv",nemarcat"
EXPERIMENT
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GENETICA MD
#)
EXPERIMENT
HERSHEY #i CHASE, 1952
Celulele bacterieneinfectate
sunt puse intr-unagitator
pentru a desprindecapsida virala
Mediu celular
radioactiv cu 35S
Celula bacteriana
radioactiva cu 32P
Bacteriofagiiinfecteaza
celula gazda(E.coli)
ADN viralmarcat cu 32P
Capsida viralamarcat" cu 35S
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EXPERIMENT
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GENETICA MD CURS 1 - A nu se copia sau distribui fara copyright$*
EXPERIMENT
CONRAT #i SINGER, 1957
Demonstreaz! experimentalrolul genetic al ARN .
Se utilizeaz" RIBOVIRUSURI:•
VMT (virusul mozaicultutunului)•
HR (virusul Holmes ribgrass)
EXPERIMENT
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Proteina VMTIzolare VMT
Virus hibrid
infectata
GENETICA MDCURS 1 - A nu se copia sau distribui fara copyright $!
EXPERIMENT
CONRAT #i SINGER, 1957
ARN HRHR
Proteina HR
Degradare
Degradare
ARN VMT
Infectareafrunzei de
tutun
Leziuni de tip VMTVMT
Proteina HR
Proteina VMT
Infectarefrunz! de
tutun
Leziuni de tip HR
Proteina VMT
ARN HR
ARN VMT
Virus hibrid
Virus hibrid
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07@ABCD Logo$#
CURS 2 - A nu se copia sau distribui fara copyrightGENETICA MD
CONCLUZII
- poart" mesajulgenetic #i NU
proteina.
- este materialulgenetic al
ribovirusurilor.
ARN
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Unele din imaginile prezentate în curs au fost preluate dindomeniul public (internet).
• http://images.google.com •
www.google.com•
http://www.juliantrubin.com/bigten/dnaexperiments.html•
http://nucleus.cshl.org/CSHLlib/DNAinNY/Case5/Case_5.htm• http://www.allometric.com/tom/courses/bil255/bil255goods/09_dna.html• https://wikispaces.psu.edu/display/230/DNA+and+Chromosomes
•
https://deltawire.delta.ncsu.edu/around-campus/making-metabolism-easier-to-digest/
•
http://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-19/CB19.html
Genetica MD CURS 2 - A nu se copia sau distribui fara copyright
• YZ=0[[\\\KIAD#%@K"2$[="D=#"[L?%HH?H?[`%IY%H?E%A[ED#L"H"<3I[A>%HI3>?=<DHKI\@
REFERIN&E ELECTRONICE
$$
Pentru clarificarea unor probleme legate detematica predata la curs se pot trimite
intrebari la adresa:[email protected]
NE REVEDEM
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NE REVEDEMS!PT!MÂNA VIITOARE !
LUNI7 martie800 a.m.