Z Sa Sa Se a a a Pa ea a a a ea a a Fe eo eS a Se a Se Be eS int} -The science which study " "inheritance" vheredity” -The science which study how cinerea: "traits" Ad or information transmitted "passed" from one generation to the next. we - The basic (essential) (foundmental) unit of life. (Cell structure: | 1) Cell membrane 2) Nucleus ———> contain genetic material 3) Nucleolus ——— > contain RNA 4) Mitochondria ———» contain DNA vaede Nucleus © IL ce\\ mito chondria membrane POPPE OLE I II LOO OOO LI IEEE ELE LEE IEEE IEEE EEE IEEE EE IEE PROPEL LLL LOLI ELIE EOI EOE EEO EEO ELE EOE EEE OEE OEE EEE EEE. Sperm Zuo $ @ 5 Fusion G>) divided to form Trillions of cells ———— Ovum Zygote GC fo) Fe Sa a ia a My a a Me a a Me Me a a Se a a Me My Ma a Me Me ee Me ee Me Me Me Me Me Me Sea Si a a ua a Pn a a a ae a a ea a a a a a Pe a Pa Me a a Me Me a @} Types of cells 1) Nucleus 2) Number of chr 3) Specialized Cell acco to Nucleus ate Gere 1) ~E cell 2) Eukaryote cell - Cell without nucleus - Cell with nucleus 1- Cells according to number of chromosome FA De, wats 1) Haploid cell 2) diploid cell - Cell has@3)chr = cell has@3)pairs wy ap Ex: Sperm, Ovum zygote, Somatic cells 3) Cells according to specialized Ate ah 1) Stem cel 2) Differentiated cells - Not specializéd - specialized - Can divide -cells that have specialized - Can differentiate in many - use small part of genome PPO PEO OO LOO OO OOO OOOO EOE EOE OEE EOE EE EEE EEE OEE OEE EL Possible kinds of cells alr elt PPPOE L IL OL OIL OOOO EOE E OEE EEE EEE OE EOE EEE EEE OEE ELE Fe Fa Si Fe Sa Ho Re Fu Fe Fa Fa Pa Fa Pa Pa Pa Me Pe Pe Me Me a a Fa Fe Fe Fa Pe PP Pe g g @ @ % 4SESSA ESSERE GEESE —nr ts C) )— Nucleolus (RNA) Chr=DNA+ Protein | - Chromatin=DNA + RNA+ Protein | —___________+ wore 1) Composed of : 2)23 pairs=46 chr = 3) made of two DNA and Protein sister chromatides are held together a. by centromere i Noteey > 22 pairs ( Auto some) 23 pairs 1 pairs ( sex some) * male =44+XY * Female = 44+ XX eee as tro were Cen : (Chremesome) Beaute Raa eRe Rea Bee Me eee Hae Me a Me BeBe Me Mee Me Mee ER ChromatideSePeRe esas ese esa a Ra a eee eee es ee erate ere E Fo a Se a So Gel 1) Deoxyribo 2) Store genetic 3) present in nucleus, nucleic acid information mitochondria 4) Can copy it self 5) Passed from generation to next FR RAI II I tse nN’ - DNA composed of cone tee units aed "Nucleotides" - DNA is polymer (mac alecule} of nucleotides © * si ber - Nucleotides are building blocks of DNA. - Each nucleotide compossed of "sugar+ N.Base + Phosphate" EOL OO OO OOOO OEE EOE OEE EOE OEE EEE EO OEE EEE 1 | w, gree POLEPLELIT LETTE ELLE EE LLL EE EEE E LEE E IIT a a a Sa Pe a Ha Pe a a a Pi a Ha a a a ee Hae Pe Fa He Pe a a Me ee Ha He2 * Back bone: consist of "sugar + phosphate" bind with "Phospho diester bond" between 5 and 3 carbons. *Nucleoside: nucleotide without " phosphate" ar" 8 sup! Se * Nitrogenous Bases* Paci oo (A) (G) (c) (T) (u) Adenine Guanine cytosine thaimine Uracil - Base pairing:- sha} er en To eeSall . eaten ne The arrangement of the bases in the DNA is not random * (A) always bind with (T). A * (G) always bind with (C). G - Base pair (bp):-Unit length of DNA. * If DNA is 120 bp = 240N G=80N c=80N A=40N a T=40N oe, PPO LO FEO OOO OOO OO OEE EEE EEE OEE EOE EEE EEE OO EEE EEE EE PPE PO LILI I SL LO OOOO OOOO EOE IEEE EE EOE EEE EEE EEO OEE EEE ELE z 2 2 2 e e @ xX g e e e 2B e 2 ¥ é e Be ¥ @ e e e eB e e eBe Fie a Pie ea fa a ae a a a ea oF oa ee @ @ @ @ e ¥ Z @ ge 2 jy. - DNA exists as two stranded twisted together to form "double helix" - Each strand is a polymer of "nucleotides" - Two strands being held together by “hydrogen bond". - 5' end of one strand at opposite 3' end of other strand. -Two strands are “Antiparallel" ~23t obsb~ — - Two strands are "complementary", 4 wa Ae ioe 1) The smallest unit of inheritance DNA instructions for making 4) Segment of DNA “Specific protein" t “Qahe oo * Genome: - The Gn of all genes in the cell Foor eo nok SRP E LL LL LI IO OOO LOT OO OEE EEO EEL ELE EEE LE EEE EEO ELE | | g a 4 a a 3 % 2 2 2 j ¥ q 2 2 2 2 ¥ yg j ' 3 3 4 B 2eS a aS a a a a a Fae ae Fa a en ae a He Pe a ee eo 2 “aA * Genome: - The complete set of genetic instructions in the cell include nuclear and mitochondrial DNA. | becation | Nucleus, Mitochondria | Nucleolus, cytoplasm esa eae ee a Number of Two strands One — 4 stants Double helix Single helix GOP PLETE EEE ELLE E ELLE LL TELE LE LE LL EL EL ET TET Eg PEPE ILOILO I OOO LO OOOO OTE EEO EOE OLE OEE OEE EEE OE EEO OE EEE Fa Se fa Sa Se Fe Sa a Fe a a Pe a Fe He a Fe a a Pe Me ae ae a Ha Me Me a Me 2Foe ne i i i FFF 6 Fs Ss Fs a i i i ee a a a ey My a ci Gellevele - Group of events include:- 1) Mitosis (M) phase 2) Interphase (™) (Go) m S e oe ea ia Go:- - et phase ape - Call décide divide die or stay Ji Pfeventiated - f - Outside the cycle 5 col inter phase:- Phase between two mitosis - start with G,,S,G, * Gap1 (G,) — cell increase in size - any damage in DNA must be fixed oar Ones * G,/S check point: control mechanism that ensures that everything is ready for DNA yes replication. -(S) phase (synthesis):- At this phase DNA is replicated Se Sa aS aS a Fa a a Fa FF a a FE HEFF SF FF a Fy i i a a Fa a Fe Pe Se a a a Pi i a i i i i - G,:- - cell continue in growth 2 - Centrioles duplication - G,/M check point: - control mechanism ensures that everything is ready for mitosis Cell replication centriole Volume of DNA duplication - Mitosis (M) phase:- - Cell stop EN. a ‘ - Cell energy foucced on mitosis * (IM) check point: - in "metaphase" - At the end cell divides to two cells . RRR RARE —oshes - Duplication of DNA. ratio - Forniation new copy of DNA * Steps of replication:- ng of en (1) 4 > Ss 2 ‘ 5 FF 4 06 FFF FFF HEHE FEEL EERE3 SSSSESEA ESSER SHAE EU ESSN SENSED SERED ‘ ol Xasw (3) 1) Topoisomerase: Uncoil double helix (relax) fies. Origin of replication Sea ears 2) DNA helicase: break down hydrogen bonds at multi points called “origin of replication" ye - Separate two strands (unwinding) caa INNO ‘ AA £56 7, * Single strand binding protein (SSBP):- Help in keep the strands a part. Wes Teele Lagging strand Leading strand = DNA polymerase a Terai Template ama peonee— +53 aus alss 4) RNA primase:- bind RNA primer at initiation point of replication. 5) DNA polymerase:- Add new nucleotides to syntheses new strand. cee create new strand AAAAAAHAHAAAGDRGAG EGHAMa FV a Fu FF Fe a a la a a Fu i i i ie a He a a Fa a a a a i i He a N « Leading strand:- continuous strand. = * Lagging strand:- dis continuous strand. Okazaki fragments 6) DNA Ligase:- Join(link) Okazaki fragments and two strand ny os ( Conserved) —— ®»® TGTAACGAA CA A. C_A_T JG & 726.7 ALATI GettGcr®r wef TGOTAS Cer sek A&C ATT Sey eT 2 Ol{ooreper)( Pair ex¥ ) Fs ue Fe a Fe Fe iF Fn a a a Pa RMR RU RH Mae DESFie Sia ae Se Se Se a ea eae Se Re Se Me Se Me a a a a Re Re Se Se Me Me ee He Me Me Me a Me athe utjuman genome) * Genome:- The complete set of genetic information in the cell include Nuclear and mitochondrial DNA. @ PRE RE POPPI EEL IL OOO OOO LOO OO OO OOO OOOO OE EIT LOO TOIT sien OD 1) Nuclear DNA i 2) Mitochondrial DNA Nuclear ONAY ei A Ny Ble Sas 1) Gene and gene 2) extra genic Related sequences DNA 25% of DNA - 75% of DNA 1) Coding DNA 2) Non-coding DNA 10% ¢ 90% PPO I OT I I I TO OO TO I OO OI OO GE OI EOI IEEE EEL OEE IEE LS. Bethan e a Mae a Bae Ma Me My ee Mee Me Mea MaMa He My He Me Me Me Me Me Me MOE2 _£Organization of gene* Stopcodon S$ PIII II II I OO LO I OOO OO OOOO EEO OOOO EEO EOE EES EEO EEE EEE ES eon Terminate CAATA GC TATAA exon intron eamscri en box box box * 5' promoter- start codon —exon-intron- exon-stop codon- 3' 1) Promoter:- oh we, bated - Signal for initiating transcription. - Consist of (CAATA — GC — TATAA) box. - ParT oF DwA: 2) Start codon:-_ P eT ans) at - Correct initiation for transcription. - Always (ATG) ——> (AUG) 3) Exon:- sation xed - The functional portion of gene. - The coding region of gene. - Number of exon = Number of introns + 1 4) Intron:- - Non- coding region of gene. = OZ. removed after transcription _~ Separate between two exons. jee PRI I LL IL II IIL OOOO OOOO ILO OEE OOO EEE OEIC I IEEE EEE ILE Be v4 vd Bg yg Be VI e e e Be B e g 3 3 I Bg Bg Bg 3 j Z Bg e 2 e e e e e g 8 e ee g eB g eg eB e % Fe a Fa So a a i Ba a a Sa Ry a Me Sa a a Ba Me Me oY bh 5) Open reading frame:- eg ge es ge 3 % PPI ILI I I LLL LO OT OOOO I OI OOOO OO IO OO IO EOL IIIS Pt cd) e= Sequence with variable length does not contain stop codon. - Start with (ATG). - Can be translated. 6) Termination codon :- - Sign to end translation. e located at 3' end. - could be (TAA, TAG, TGA). 7) TATAA box:- eye - Function: Direct important enzymes to correct initiation for transcription - Region about 20-30 bases at 5' end. - At the left "start codon" POI OO OOOO OOOO FIFE OOOO TOTO OEE E. oe , x g 2 2 g @ g @ 2 Be Fa Fa Fa Fa a Fe Fa So a Fe Me a Pe Me Ma Me Me Me Me Ma Mo e @ e @ @g 2 y ge Z 8 ge eB @ eB 2 z S B Bg vA va B 3 3 3 2 Be 2 Be 2 3 @ app ass) Sloe 1) Unique single copy genes 2) Multi gene families ae pie) ys | * Coding for polypeptides that z *Many genes do ase aS Perform variety of functions ». similar function s — ae in the cell 1) Classical multi 2) Super gene Gene families’ families lies | * Have high degree bapa, Have limited a of sequence homology degree of woe sequence homology FES IE css 1) Double strands- circular in shape. aint 2) All genes defined in mitochondrial DNA (37 genes) 3) 93 % of gene is coding. 4) Inhertied from mother only. ow POEL LI I LOL OT OI OO OO OI OOO ELE OEE EEL EE IOI EE PIPL IOI IL LIL LT LE LT OO OOOO OO OEE EEL OIE EL EEE IEEE LD: 4 g g 2 e 2 2 g@ 2 2 @ e 2 g 2 2 y 2 g e 2 xy B g ge g Be 2 2 x 2 2 2 2 @ 22 Bg eg 2 2 2 2 2 e 2 2 Y @ Z ¥ z 2 B 2 @ 2 . 2 2 uy 2 ge 2 2 ie Og * Two genes code for *22genescode *13 genes code rRNA for tRNA for polypeptide used by mitochondria FO CK == 1) Every three bases represent "codon" . 2) Every codon represents "amino acid" 3) Number of amino acid 20 AA. 4) Number of genetic code = 64 codon 61 3 f active stop codon POE IE EEL LL EL IL OO ELIOT I IEEE OO OEE LOL IEEE EEO EEL. PREP LOI ILL L OL IO EOE IEE LOO IEEE IEE ELIE EEO IEEE EEO E RA AAASAESARSSARESSARASSRNSARSSSRSNESEeo % POPOL ILO IOI TO OOO OO EOE OEE EEE OEE EEE EEE EOE EEO LEE EE a Fin a Sn eS aS a a Fa a Se Ma aS Fe Re aS Be Se = - Foon mRNA from DNA. @ e e@ @ e e e ayy -The ane of RNA under the direction of DNA Jas - Transfer of genetic information from DNA to RNA. wi - Take place in nucleus in eukaryte cell. ayremineess on - Only one strand of DNA serves as a template for Transcription. - This strand called "Anti-sense strand" or "Anti- coding" ((#5=- Template” - The other strand called "sense strand" or “coding strand" ((non- TEmPlAle? sense strand se AACGTINGC GAAS TAGE eC Me TTC CKAASETT OAT CECE ae G = = - Transcription divide in four stages:- a3! A) Initiation B) Elongation vu c) Termination D) post-transcription processing aw tie 5 aaa aad ah laa ea Pg Z Sa a a Fa Se a Fa Se Sa a Se Sa a a Se Se a Sa Se Ma a Se Me ee Pe Se ae Se Ma Se Re RRPip Ri Bia a a Be Bi Me Bin a ie iy Me Me a a Re Be Me Ma a a a Ry My Ma ee Be Me Mi Be Re Ry Me Bie a Re al aor i Lh pls A)Initiationstage = we TI ion RNA (1) wh e Bpel@teatenm— +! - RNA polymerase Ili OOO OO OOO OL OOO EO EOE OEE OOOO OO OOO OO OOOO OE EOF OO EE FE DNA in the 3'-5' aw wr 4 ble bi 10 to 20 DNA ELL RNA wel 3 RNA : Ba Paeges Cetera ereIonn sass DNA z & és! RNA mage 5 RNA DNA et)hantaee} Aigsy elokeribokage Lalo vaa gap spo aae rest ualsWcsls\s} oma OyS) aeyioy 2) The Ries FAP Hab mooy aR Me Mara INP reKIce!Re S) SHURA ipay a yteteay ot hope pCa ye Fina 1%Sa Si a Sa Ba a Ha Fa Se a Sa Se a a a a He aS a a Hea a Se a Se — ~ “Post- transcription modifications" ys e e 5 af - Include three steps:- 1) MRNA splicing 2) 5'- capping. 3) Poly adenylation. ey e - Remove (spliced out) introns- exons rejoin together = - Pre-mRNA converts to mature mRNA. @\e \ - Addition of a methylated guanine nucleotide to the 5'end * The 5-cap function:- 1) Facilitate ceareparit mRNA to cytoplasm. 2) Facilitate attachment to Ribosome. 3) Protect the RNA transcript from eatin by exon nuclease. die Addition of approximately 200 adenylate residues to 3'end Addition of poly (A) tail. Be g e B g g Be SOPOT OO OT ET OE ESE E FEET OE TE EEE EE OEE EEO EEO OEE. ff i i, ce: : III I OOOO OOOO OEE EEE EON OEE Sa Sa Rea Me Ba Ra Me Ma Ba Mea Ma Me Me Ma Me Se B 2 2 2 2 2 2 g 2 Z a B zEn En En Fe FF FE FE Fn FF FE FFF FF a a eee Pe ee eee aS OR a : - Cleavage of the 3'end of the mRNA from DNA to 8 facilitate transport of the mRNA to cytoplasm. 8 4) DNA regions that can be transcript are called 8 “structural genes" ais le . @,,. f 8 z oe} : 3 : s : : | : Oise ee ee PPI LOI IOI OSE OI EL IEEE EEO OLE EEO EEZs. - RNA directed synthesis of a polypeptide. oF, Convert genetic information on mRNA to polypeptide. aedos - Take place in cytoplasm on ribosome. & z 8 & ‘ 5 & & & & & & & & & s s - mRNA template - Ribosomes- rRNA 8 5 & & 8 & & : : : & R - Transfer RNA - GTP(source of energy) - Trees¢ripten divide in + stages:- yw &. = wy A) Initiation B) Elongation c) Termination iw) er sw - mRNA migrate to cytoplasm. - MRNA bind with a small subunit of ribosome. (BvZo Me initiator tRNA with the anti-coding (UAC) base- pairs with the start codon (AUG) —_ x =f ~ Arrival of large subunit of ribosome completes the PRI E ELI L II LOL LOO OOO OOOO EEE L EOL ELE L EEE O IEEE EOL IEEE ES- The initiator tRNA carry the amino acid methionine (Met) - The initiator tRNA is the (P) site. sie : - The (A) site is avanaliie to the tRNA bearing the next (A.A) POP IOI EOE E LIS - The second tRNA base-pairs with the mRNA codon in the (A) site. a - rRNA molecule of the large subunit catalyzes the formation of peptide bond between the new (A.A) in (A) site with (A.A) in ( P) site. - The ribosome translates the tRNA in the (A) site to (P) site. - The first tRNA in (P) site moves to E site to release. - The next tRNA is coming . - When ribos: reaches a stop codon, The (A) site of the ribosome accepts a protein called "a release factor” instead of tRNA Se os . abt 7 The two ribosomal subunits and the other components of ‘the assembly dissociate aa POI LI IEEE ELLE ELE LEE O OOOO LEE EEE EEE OEE TOLLE LEE EEE EELS PELE LESLIE LOO OOOO EOE OOOO CECE EEE EO OL IE: % 8 g @ g g @ @ e @ g g @ eB eB Be eB B % Bg @ @ @ eB % Be B @ Be e 2 B g e @ @PII IIE IOI OOO IOI OOO SOO OEE OOO EEE EL EE EE EEL ES SPIae eg Bg Bg ge ge ge Bg Bg Bg vd Vd y Z Bg ge Bg Vd vd ge ge @ e B Be eB Z eB g ge ge ge oe e 4) Translation the second stage of gene expression. otha - The process of the transfer of the genet DNA to RNA to protein. formation from - Protein cannot be converted into RNA or DNA. cw, - Sequence of bases which codes for the order of amino acids in polypeptide. (2) Ribosomal rRNA). Y2F - Join with various proteins to form ribosome. SRIF LILI LEI LE LTO OOO I OO OOOO EE OIE LEE IEEE LILO EEO E LE & - Ribosome = rRNA + 55 proteins o£ . Vital in translation. etAieeslt - Correct spatial orientation of aa. 3) Transfer (¢RNAs ~ 4) Small molecule (73-93)nucleatides. 2) Lower MW than rRNA. 3) Single stranded (clover leaf shape) eee 4) Two ends a) Binds a.a at one end. b) Binds mRNA at the other end. ge g g g g g @ g @ @ g 2 eg eg eg e 2 ¥ e @ @ e e @ e g @ @ @ g g @ @j ; eB eB Bg eB 4 2 g g ; 2B eg S ge eg 2 eB eg Bg eB Be ge e 2 3 2 ; eB e 3 Y se ee i} ys - Adaptors to correctly order a.a on mRNA for protein synthesis. 2 - Sites which base pair with mRNA - present at tRNA - The site of protein synthesis. - Composeg of(rRNA + Protein) Endep - lactated in cytoplasm (Free) or attached on (ER) ere ie - Two subunits (small and large) - Large subunit consist of (A) site, (P) site, E site. a - Translation of information encoded in the mRNA. ar. Holds mRNA and tRNA together. - Form peptide bond between a.a. POI LOL L LO LL IT OO OIL OI LO OIE ELLIE - Enssures accuracy of protein synthesis. wee a> POPPI L LE IIL LEE EO OOOO OO OOO IEEE LOO IE LO OLE EEL O EOL OE EES A a a a a he a She a Se a Fo a Fe a See See oe Fe ee Se i ae ee Re Pe Se a He ReLec 6 RE S ow Vary Canta :- The science which study chromosome and cell division . usr $ * Chromosome: Formed of DNA embedded in protein. é 4 e hed one species oye ~ Acts as factor which disti from another. - Facilitate the transmission of all genetic information FeSO IO ICI Kk PMS ght - Chromosome made up of - Chromosome: Supercoils of DNA * consist of two sister - Chromatids. * Divide by centromere rece (shert)} into two Sims. eles tip of each chr1) Telomere : sign to aging and cancer. 2) Telomere: effected by the activity of enzyme called Pye) 2“ “"Telomerase" seek iar =a : tk Chromosome classified according to three parameters: esence orChromosome according position of centromere @ - Chr has two - Chr has one short [caiece ee - Chr has one equal arms. arm and one long KON - Chromosome divided into 7 groups according to the above parameters. arm and satellite. 1) A=1-3 2) B=4-5 3) c= 6-12 +X 4) D= 13-15 5) E=16-18 6) F=19-20 7)G=21-22+Y VA Seon - Homologous pair of chr:- a pair of chromosome with the same genes one from mother and one From father. Re Fu Re Fao Fie Ra Fu So Fie Sie Re Siu Se Mia Mo My Mieig Types of banding Toe se |2)G- Banding! Ri Fe Rie Ren Ro Sie Rie Ro Bu My Ma My My My My iy iy My By My E pele! Ib wt i Banding (stainifig) techniques i so os : | “ iy ghee mportance pe E =e a =e sb & Sui) x wt = 0 ee eke ze Be Two main forms 5 Py BD Heterochromatin, a Be iit [SRC in i wcawsacat) wes actve mind active ee = pu we we ® wb 4)Q- Banding. 2)R- Banding. 4B: s Bocas Ex) 1) G-Banding e 5 ae =) eZ sa | | trypsin then stained: ob SO OOO SO FO FO SO SO SOS 0 Seo Bio Ro Ee Ee SyPa Rel el i So a ai aa eee IS 1) R-Bands 2) G-Bands - Stain light - Stain dark - GCrich - At rich g5 - Have the highest ~ Have relatively gene density a2 few genes than R-Bands See Oboe - Itis similar to that - requires examination 4* obtained with "Giemsa with “ultraviolet tidy ufstent mnietoscope" Fleurscent wicrescope 2) FORE Telemave - The chromosomes are " heat — denatured" then staining with "Giemsa" eas SR RR ERE Conern eve - The chromosomes are pretreated with "acid" followed by “alkali" then "Giemsa" ws 2 he Fa Fan Fe Fu Fe Fay So Siu Me Hie Se Me iy Ro My Ma MyPFs Pa Pe a Pea a Pe 1) Female = XX 2) Male = XY e The "Y" chromosome:- is much smaller than (X) chr. SSO EI RE 1) (SRY) genes ee 2) Other genes important - Testis determining in “maintaining sgereto Factor Bap S fer mategencs wae rey 1 wo Tie Fhe Fan Re Fa Fie Fou Fis So Fie Sie Riu Me Bie Ba Re Se MePE Annes Cell division IPS . iy —— . 1) a 2) Meiosis leas - “ek in - Occured in (germ cells) w shinai cells" | Me. Cell of sex organs SkinLiver LungKidney J. O wi @m (4 ee ped Testis Ovaries 2" diploid 6 e” ae aur - 2 daughter cell - 4 daughter cells ee Fe FR Fe Fa Fe Ti Fi Fl i Sy Se Me Me Se Me Mi My Hu By i lySSS Sei S ih GSU CEST STEER RETRY "ae | 4eqygnep Zz aonpoid (Z / : — ES ee1) Prophase ~~~’ (mitotic) OP5,% spindle fiber — ohn Centeriolles aa 2)centeriolle jot 3) Appearing |e of spindle fiber the cell ua Sa Sa Sa Fa a a Sa Sa a a a aa aa Me ELCESS RAN 2) Promote phase wD eS! 5A) Nuclear membrane breaks up oe XD chr spread around the cell OD sian Centeriolles move to opposite poles of the cell fey Attached Each chr become ed from its centromere with *R >» mitotic spindle Ade MISBE Sole FEE 3) Meta phase obas seek Chr become align equatorial plane or plat of the cell Chr become maximally Cee ‘ contracted "easily visible sy \—> BS a) Chr reassembles (X) letter ack chromatids separate but — remain attached by centromere paral hu Fa Fa FF Ph Mu Pi Si Si Hy Fe Me Me Mi i Ma Me a Se4) Anaphase Ss Centromere of each (chr) divide longitudinally ,) oom Two group of chromdatides ave formed. OH) see Mitotic spindle contracted then a pulls chromatides FEE I I OHIO * Telo phase -Each group of chromatids envelop by nuclear membrane ® o <— ie Fi Fe i Fa FR Fi Fe Fe Pe Mi ie Mi Mia My He Me My Bi -Each group of chromatidsseparate completly ° Cytoplasm dividion (cytokinesis) ire NNLN1) Occured in | t a" germ cell" sa Lan i a a Ho Fa Hi May a a Se a a a Ma Ma aaahProphase B.-5 aa «. *Include 5 stages Sete - . eS = FEISS IO IIE * Leplotene* 4 1) chr begin in ; : i 2) chr become yey a z pes FIRE ye Fe ee a He Ha Ha aa a a a Sa He Ny a Me a a aCAESARS a *Zygotene* WA) Suge wy ¥, Homologous chr align directly opposite each other ® Held together at several points Be begin in pairing Fone ek * Pachytene * “D, Each pair of homologous chr become "Tightlycoild " (Zoy-i,.1- a Each pair of homologous chr formed " Tetradis » zolehs Fan Fa Fu Fe Fu Fu Fa Fa he Fi Sa Me Mi a Sl Mi a Hh Sua Fu Su FR a i Mi a i a Ba Fy a i a ee i i iy 1 Diplotene as Chiasamata on ee over Sue asl Seesesteare erect ey ehn nqc Vetter ae Tie omelogeus chre mo Some - * Diakinesis * - between Two —— <- io : Begeed sel EOE Fe FF FF Fh he ee He Ha aM Ma Mi My: Fa Fu FF Fe Fu i in Fe a Re MH a Hy a Be a My a ey iy * Metaphase | * = ‘D. Nuclear membrance break up 23 The chr becomes align on the equatorial plane of the cell "Z\ The chr become attached to the spindle fiber JSS Sx * Anaphase | * % Spindle fiber contract Centromere not divide @ The chr now separate to opposite poles of the cells Fh Th Fi FFF Fh Su SM PH ee Se Me Mi Me lS lya Fig FR hi in Sa He aH Me ya a Ry a yy 4) Telophase | a OS completely to opposite ends. - The cell cleaves into two new "daughtergametes " = - Daughter gametes called " oocytes" or" spermatocytes " aero 3 Meiosis II we - This is essentially similar to an ordinary " mitotic division" - The cell splits leading to the formation of two new daughter gametes known as " spermatides " or" ova" s2ph' E ~ Each set of haploid chromosomes has now separated me Fe Compare between Mitisisvs Meiosis Fae Fa Fu FF FF Ss ly Fl ee Hy a a le Sl Sy= - Gross lesions - Accounts for Cede: rH ivigguuuna een ‘* Mutation * - at change in nucleotide sequence. * The cause of mutation : Pe 1) Exposure to mutagen! ic agents.( induced hb ae — a ae 2) Errors during DNA replication and repair.(Spontaneous ) 5 * The level of Mutation * i 1) Chromosomal level 2) DNA level S A i" Less than 8% - Microlesions - Accounts for more than 92% ean esti)! | 2) Structural abnormalities The occurrence of An increase in the number of One or more extra’ be haploid sets (23) in a cell or missing chr. Suh wry a Fhe Fhe Fl Hi Hi Mi Me eM Mo Ma Me Me My a a i iy Mh hyPRE ae Z people have normal one chr ae pair of chr plus an Be | ~2n= 2048) F extra chr consist of -Turner ? || two identical short syndrome _afms and centromere | -444+x0 ine ; -Down syndrome - Kline falter we ye we ze oe a Pao Se 45 +XY = 44 + XXY ie - 45 +XX - Chr (23) = - Chr (21) = Se Ee & HeonE oe eo By y xe - 1)" Tri riplold yin, ee) Tetra 1 Ploidy _ & z Oe al 1 é People have Four a | | haploid sets of chr ina :| ale § if P4 Gn) —(Bchr per cet | @)Baenrpercen Ay = ey & ae Fr nnnnnennnre reed ee Te Se Bly Ma Ma Be Ps Fea a Fe Hh he Bla My a hy hy Bip iy Ma iaEne Fe iF Fa iF a iF al a aa | | aoe oe : r ob, wu! zs ey 3) inversion 4) Translocation 1) Deletion 2) Insertion Loss Add part of chr part of | part of separate and | chr | chr , feattached in < \ om ee RAG ee position wor as 1) Somatic cell 2) Germline cell 2) Coding ~ Sequences 2} Non-toding : , Not affect (2 Recognized as an inherited disorder , cle we . * Polymorphism:- change with no effect in the phenotype . - Common variation greater than 1%. * Mutation : Rare genetic change alter the function of protein. -Lessthan1%. "7a ASEH cab Hoek wy ia Fa Fa Fa Pi a Mi Hl Hl Hla Re Ha Ma Mie Me Mi Mo My Me My Ma Myinto MMos oad * Splice site mutation * . FEC E REE EE dibot Inserts or deletes in a number of nucleotides in the site splicing of anintron. .\3\, Lead to abolishment of the splicing sit Results in one or more introns remaining in mature mRNA Lead to the production of aberrant proteins. 5:35. eee os * Several genetic diseases may be result of splice site mutation. Eg. Mutations that cause the in correct splicing of B-globin Causes lassemiat? e JaecorerE EEE : ea dupes o of mutation according to he v p22) | 7 Transmitted unchanged - Undergo are S262 (Unaltered) __ they are transmitted P 0 ea eae aan ~ * Fixed / stable point mutations can be classified according to immgic naiee molecular _—_ sation 2) insertions rerions || os Deletion eu \ o> 4) Paallcationeoly v1 Sige | iB) 1) Substitution: is the replacement of a single nucleotide by another. eee EEE EERE Substitution 1) Transition 2) Transversion C for T or vice versa A for G or vice versa Jobcoeeeeoee 2) Insertion: Addition of one or more nucleotides into gene. - Ifan insertion OCCURS in a coding sequence and involves one, two or more nucleotides which are not a multiple of three, ee - It will disrupt the " readingframe” 3) Deletion:- involves the loss of one or more nucleotides. eee * Dynamic/ Unstable mutation * oe Oe Swe - Consist of " Triplet repeat sequences " - Occur increased copy number when compared to the general population. eeeF. as cai Structural effects of mutations on the protein * 1) Synonymous/ Silent 2) Non- Synonymous - Mutation does not alter - Mutation lead to an The polypeptide product of alteration in the encoded The gene polypeptide - Asingle a pair substitution = - fanereton OF the amino Result in another triplet acid sequence of the Which codes for the the protein " Same amino acid" aa East he ae - No Alteration in the properties of protein aoe * Non- Synonymous mutations occur in one of three ways* 1) Missense - Asingle base pair substitution can result in coding for a “different amino acid" 1) Conservative substitution | 2) Non- conservative yo Nd v sists - If mutation coding - If mutation coding — Amino acid which is _ ino acid which is chemically ically similar il | - Result in complete loss or ) gross reduction of biologicalCy * 2) Non-sense sats as - Asubstitution of base pair leads to the generation of stop codon. Sel WY Lead to premature termination of translation. Result in reduce the biological activity of the protein. Involves the insertion or deletion of nucleotides which are not a multiple of three. A frame shift mutation causes the reading of codons to be different. Bai It will disrupt the reading frame. The protein being created could be abnormally short or long. Frame shift mutations result in severe genetic diseases such as "Tay- sachs" Responsible for some types of "familial hypercholesterolemia" PREYS EY eeeeanneeeeeeee Cause either reduced - Result in either increased Activity or complete loss _ levels of gene expression or The gene product the development of a newfg) Loss of Facchten Gan of fumed: igs L Ju - Haploinsufficiency :- associated with _- increased levels of Half normal levels of the protein gene expression Product responsible for (CIMT) - Occurs when a diploid organism Only has a single functional copy of gene. FO II IOI IK Notes 54. oy e Dominant — negative mutations: A mutation whose gene product adversely affects the normal gene product within thesamecell. e Usually by " dimerize" "combining" with it. Heo eee \empanbaes genetics importance of mutation * ** Low activity_pebedy Shes Mutagenic agents peas HoneEEE rs iS Mutagensis:- the process in which genetic information for gee \\) individual are changed in a stable maner. Mutagens:- environmental agents which causes mutations. See Types of mutatio 1) Chemical 2) Physical 3) Biological FESO RA Kr bemical Muta ene ce 5 Whemical Mutagens” 2s - Contribute by 35% of cancers.3) Agents alter DNA structure cpt Free radical (OH) 4) Agents Altering _ Base (Nitrous Oxide) FOS oR ck (apizestor™ - Length wave ———» 260nm _> Poor penetrance, _ #230"! u&* Absorbed by DNA and RNAbases. - Result in "pyrimidine dimmers" ((CC-TT)) SoHE EIX-Ray Gamma-Ray Particles - Gamma-Ray —» Cause See aS H On a Affected in DNA structure Fe 1) Transposon _2) Jumping genes 3) antbiegem x resistance Insertion into me ies genes Transposable elements move ¥ in different Disrupt reading position on chr frame — v Loss function- DNA repair mechani - DNA repair mechanism exist to "correct DNA damage" - DNA damage due tom” 1) Environmental mutagens. 2) Accidental base disincorporation during replication. _Types DNA-repair pages Excision repair Mismatch repair Double- repair Excision repair - Removing one strand with damage DNA site. - Excision repair can be. ee Base-excision repair Nucleotide-excision repair <5 | 1) Recognize by repair protein complex (XPA,XP5 ,XPc ) ~ 2) Excision by exonuclease Excision (27 N) before and (29N) after. 3) Synthesis and link by ligase. Sau Podymeras epire Mismatch repair system - Correct the errors of replication. - Eight gene loci ( MSH , MLH , PMS) 1) Begin by removing the strand which has an error base. 2) DNA polymerase II! Synthesis strand replace the ns damages strand. Notes: - Failure in mismatch repair leads Ro s Micro satilate instability (msi. ye! © +~“— Sporadic tumers have HNPCC Tumers have 10-15 5% (MSI) _ a 95% (Ms!) seeseeerenenenenees Replication repair system DNA damage interferes with replication and transcription. In replication: DNA damage will affect the leading strand. RNA polymerase: cannot use leading strand in transcription HEE ERE Do ble DNA-re pair Double-strand damage is a common consequence of gamma radiation. The process require 3 important gene 1)ATM 2) BRCA1 3) BRCA2See ee 77 Pe Fe wi Patterns of inheritance FEO OIE EEE . vu! peso Je - The manner in which a particular genetic trait or disorder is passed from one generation to the next. FEO IE Modes of inheritance 1) Autosomal dominant —- “=? %— 6) Y. Linked: 2) Autosomal recessive ——- “** “~~ = 3) X-linked dominant ——— * es cS 4) X-linked recessive ——- ~*~ ene iieeiect 5) Mitochondrial inheritance Ae z FORE HK adhe * Pedigree: A chart of the genetic history of family over several generations. see EERE EE Definitions ye : A piece of DNA that encodes a particular Trait. : An alternate form of a gene. y= : The ph physical expression (aapeerenes) ofa gene or allele. 27 : genetic composition of an individual : The location of a gene on a chromosome. POPOL LOSS : expressed whether alone or in pairs. : expressed only in the absence of a dominant allele. 8) a: the genetic composition of an individual. ats SH Sa HF Sa Hae PreprereremmerremrenerrTEtt Sa oy souFa Fe Fa Fa Fa Fa a a a My Ma a a i Ma i i i i i (2 Genotype = Bare ee Ses a) Homozygous b) Heterozygous & * Containing a pair of the same * Containing two iy alleles TT, tt different alleles Tt & BN ete), > & {© Autosomal Dominant inheritance ~ : 1) Mutation in only one allele is enough to express the disease. Sop Sys & 2)The disease is observed in multiple generations. : 3) The offspring have 50% chance to have disease. 4) An affected person has at least one affected parent. 5) Both male and female affected. Se Ald of | Be | Bs S Examples Jivfas bye 1) Mar Fan syndrome: - * Connective tissue disorder. * Gene in chromosome 15 q 2) HuntingtenDisease: - * choric movement disorder. 2S * Gene in chromosome 4 P. WisesLeo be [2] _ Autosomal recessive inheritance NE) Atooninsicionaee FREE RE BS sf ts 1) Both gene alleles need to to be affected in order express the disease. f & 2) The disease is observed in only. single generation. = = i” 3) Trait often skips generations © 4) An affected person is usually born to unaffected parents. & 5) Both male and female affected. a) ene a fibrosis (CF) z 6) Consanguinity: js CharacterisTi'c for AuteSemaL recessive- A single disorder, Trait caused by mutations in genes at different chromosomal Loci. 8 i at L ds, ~ ween inheritance: i nf . Hee Locushetero geneity:- ingle.dl me Traits are controlled by genes on the sex chr. fa 2) X-linked-recessive 3) Y-linked Bea BohLS ise, oe? linked dominant 1) Affected males produce all affected daughters and no opi affected sons. 2) Hetero zygous affected female will transmit to half of her children.( sons or daughters) s me C= 3) More females than males. hn eereeererrss Mee ole < x X-linked recessive ‘ RR a : 1) Usually affected only males. 2) Affected males usually have unaffected parents. 3) Trans mission through unaffected females to male. 4) No male to male transmission Affected men born from carrier mother, With50% risk of disease. eSa Fe Fe Fe Ru a $a a Me Su fl i i Me i ya ie sooo Y-Linked - Only male are affected. - Male infertility ©: @ he Fe uaF i Ma Ma Me ee Hi Me ey a My Me Myac Mitochondrial inheritance ~ Fo EE Oe gy 1) Inherited in non-mendelian fashion. an) 2) The disease is inherited only maternally. 3) Both males and females can be affected. 4) All off spring of an affected female are affected. . a iy Jue ww ° & : é 2 & oa eee Determine If the pedigree shows an autosomal or X-linked disease. : 1) Most of the males are affected —> X-Linked 2) 50/50 between male and female —> Autosomal. L a Fe Fu Fe Fhe a Pe Fy Se Me Me Mi Ma a Sy My Mu My Ma a hyDetermine dominant or recessive 1) |s dominant —+ one the parents must have the disorder. 2) Is recessive +——> neither parent has to have the disorder. hel ae : 8 s Notes:- 1) In Autosomal recessive: when both parents are hetero zygout. Aa x Aa ©e @@ AA Aa Aa ea 25% 2) In autosomal dominant: when one parent is affected and the other in unaffected approx. 1/2 of the offspring will Approx1/4 of the progeny will be affected. be affected. * Unaffected parents do not transmit the Trait. AA x aa Aa aa Aa Aa aa aa he Fu Fl Fu la a Ma Me Me a Mi a Ma Mi Me a My My He Me MMSAAS 3) In X-Linked dominant Affected fathers will pass the trait on to all their daughters. e Affected mothers (heterozyogous) pass to 1/2 of their sons and 1/2 of their daughters. Affected: xPx? xy xPx? XY xx ox xx? x’y Unaffected FRR RR IS : PIP SOG LS 4) In X-Linked recessive: e Affected sons are usually born to unaffected mother (Carrier) 1/2 of carrier mother's sons are affected. e All daughters of affected fathers are carriers. Carrier: Px? x*Y xx? ty mx oy. Affected x®x® xy me oxy XP ory ON POO LO LONE PIO ea a Pe i Me Ma Ee a a My Me a i a Ma a My oe e