Gonslensed, appears datker on EM (labeled H1 in EY Nu, nucleohus). Sterically inaccessibl ea {ranscriptionally inactive, methylation, NoGectecus)ls mae up of Neterechrmatn, 3 hele Tn fom” of TAMA ued Yo make Aiborones. Less condensed, appears lighter on EM (labeled E in BY), Transcriptionally-active, sterically shanges the expression of a DNA segment ‘without changing the sequence. Involved with ‘aging, carcinogenesis, genomic imprinting, ansposable element repression, and X chromosome. transeriptional DNA exists in the condensed, chromatin fo fit into the nucleus. DNA loops tywice around histone octamer to form a nucleosome (“be: ona string”). Hl binds to the nucleosome and to “linker DNA,” thereby stabilizing the chromatin fiber. Phosphate groups give DNA a © charge. Lysine and arginine give histones a © charge. In mitosis, DNA condenses to form chromosomes. DNA and histone synthesis: occurs during § phase. a Mitochondria have their own DNA, which is circular and does not utilize histones. Vo Linea MONA Nl Sana ave wins Cond fina Changes ASE Heterat condensed. somes) may be lous, Fond t* Feral @ nd In Nin We (oY) Eu = true, “truly transcribed.” uchromatin is Expressed. DNA is methylated in imprinting, typically represses ie tra CpG Methylation Makes DNA Mute, ie is “or Helos Mellylation Mostly Makes DNA! Scanned with CamScannerScanned with CamScannerPurine synthesi * 6-mercaptopurine (6-MP) and its pi azathioprine: inhibit de nove purin * Mycophenolate a ‘monophosph Pur *thotrexate (MTX), trimethoprim and pyrimethamine: inhibit dihyd reductase (+ deoxythymidine mono {PMP} in humans, bacteria, respectively Scanned with CamScannerge deficiencies acids reo Nucleotides a Ribose = recess . a Adenosine ea eo Free hases a a ‘Adenine fo CS ane a mo vik [vnconser babar Alantoin ADA, adenosine deaminase APRT HGPRT, hyporanttine guanine phosproxbesytvester fern phosphorbosstanseas: 10. anthineoidase fcreton (One of the major causes of autosomal fecessive SCID. [ABA tnntbtor~ Cladaibing entestatin HGPRE Hyperuricemia Gout, Vaate stones, Adenosine deaminase ADA is quiver for degradation of adenosine deficiency and ¢ Net ATE yam 1 [a ddd h rane= Maron a irae Lesch-Nyhan Defective purine salvage nt GPR syndrome which converts hypoxanthine to IMP and guanine to GMP, Results in excess.uric acl production aud dé novo pusiue synthesis X-linked recessive. ndings: intellectual disability, ricemia (orange “sand” self-mutilation, aggression, hype [sodium urate crystals in diapen, gout ‘macrocytosis,chenecothatos dystonia, lopurinal or ebuxosta (2nd line). ‘Treatment: all Pissed off (aggression, self-mutilation) Retardation (intellectual disability) DysTonia “ach codon specifies only amino acid Most amino acids are code Wobble—codons that differ in 3rd Cwebble” tion may code for the same tRNAVanino lly required ns of «J by multiple codons, Exceptions: methionine (AUG) and tryp (UGG) encoded by only L codon. Scanned with CamScannertopoisomerases helix to add or remove supercoil Tors as Lomdshpie mice me hibit TOP Mt ee meee in prokaryotes: fluoroquinolones inhibit TOBA DNA gyrase) and TOP AV. tang nh oc Pos A pirat Re GA pe Eukaryotic DNA replication is more complex than in prokaryotes but uses many’ enzymes analogous to ‘hose listed below, In both prokaryotes and eukaryotes, DNA replication is semiconservative, it ‘continuous and discontintious (Okazaki fragment) synthesis, and occurs in the 5 ¥ direction. nces (such as TATA box regions) in promoters and origins of Particular consensus sequence in genome where DNA replication begins. May be single (prokaryotes) or nnultiple (eukaryotes). Ysshaped region along DNA template where Jeading and lagging strands are synthesized. 3 Unwinds DNA template at replication fork Helicase Halves DNA Deficient in Bloom,syndrome (BLM gene. nation), Me Geeted Srovcseal tasty + Brakng SGI ids, Mealy, Ma sath mance Prevent strands from reannealing. #itils helio: In eukaryotes: irinoteean/topoteean inhibit ‘Create a single- or double-stranded break in the topoisomerase (TOP) etoposide/teniposide Makes an RNA primer on which DNA Po pin mb ON mp5, aig dard polymerase III can initiate replic La Thar oe onl an eel Prokaryotes only: Blongates leading strond ‘VA polymerase IIL has 5’ — 3’ synthesis and by adding deoxynuclestides i ads with 3° ~ 5” exonuclease Elongates lagsin: nt Dnugs blocking DNA replication often have a r modified 3” OH, thereby preventing addition of primer of precedi the next nucleotide (“chaintermination”). NA primer Same functions as DNA polymerase Il, also excises RNA primer with 5°» 3” exonuclease. Prokaryotes only. Degeacies replaces it with DNA. Catalyzes the formation of a phosphodiester Joins Okazaki fragments, bond within a strand of double-stranded DNA. _Ligase Links DNA. Fukaryotes only. Ageietwtaascaplae (RNA Often dsf€zulate in canges cells, allowing dependent DNA polymerase) that.kds DNA unlimited replicaionoyrysd age (TTAGGG) to 7 ends of chromosomes to avoid Telomerase TAGS for Greatness and Glory. Joss of genetic material with every duplication, Muted fe baslek recta uae Scanned with CamScannercleotide substitution results n changed amino aid led cons similar chemical structure). Examples include sickle cell disease (substitution of Nucleotide substitution results in early stop codon (UGA, UAA;UAG). nonfunctional protein. Stop the nonsense! tion ofa mabe of nuceides nt dvinbleby-3 ~ misreading gal downstream. Protein may be shorter or longer, and ts function may be diseuples Examples include Ditcherine muscular dystrophy, TayeSaetis disease. i tered function. Retained intzn in mRNA ~ protein with impaired or as ; eames inchade rare causes of cancers, dementia, epilepsy, some types of disease, Marfan syndrome, pla aude > Ciena), Set Mise onan amet Cieee,—uon maton muon coe oO Ba wa Aa Ga Scanned with CamScannerDIRS RIERA ISSIR Hp LALO pENBM Beth helps te TAWA hententpHos _ Lacoperon Classic example of a genetic response to an environmental change. Glucose is the preferred ‘metabolic substrate in Ecol, but when glucose is absent and lactose is available, the fac operon is Iupantg Unig of Steer activated to svitch to lactose metabolism, Mechanism of shi TSE, * Lowglucose + t adenylate cyclase activity + t generation of cAMP from ATP ~ activation of Befilaskealresaing catabolite activator protein (CAP) = t transcription. * High lactose + unbinds repressor protein from repressor/operator site ~ 1 transcription ow cee Gees Heo ua oe Qo oe 2S HO— nose om a | » = incase a pace ractiacn | Lac operon STATE ® tons ede ayia opgue | Pa — Coates tor 2 pretend) ena eee A= 3 fe senate o ae 5 = 97 -. a O89 cnet aaa Nekcoe cat Veron bet eon pec os ae a potatoe eon ome DNA repair Budentideexcision Specific endonucleases rele cc ivelin gee cena pice eae repai ligonucleotides contain to repair DNA pyrimidine dimers caused by DNA poly gp, respectively. Resins Sully helivdistorting —Windings: dry skin, extreme light sensitivity, skin lesions. Occurs in Gy phase of cell cycle cancer, feching Ht hyeapinen Nate mnt fs, arabe excision repair Base-specific Glycosylase removes altcred base Important in repair of spontancous/tonie and creates AP site (apurinic/apyrimidinic). d sation. (6 eter) ase avs the UV exposure). ‘One or more nucleotides are removed by ‘GEL PLease” AP-Endonuclease, which cleaves 5’ end AP-Lyase cleaves 3" end, DNA Polymerase-B fillsthe gap and DNA Ligase seals it, Occurs throughout cell cycle ‘Mismatched nucleotides in newly synthesized Defective in Lynch syndrome (hereditary (unmethylated) strand are removed and gap is nonpolyposis colorectal cancer [HNPCC)}. filled and resealed. Occurs predominantly in $ phase of cel eycle Brings together 2 ends of DNA fragments to tepair double-stranded breaks. Scanned with CamScannerInien Gen Iron THR ‘Catftox thon | NGsttcofon stp a scr stat Soting © Mave Nh 4 | Tanston © Protein = [UTR fein of ANA aS! and Slerdé_ hth avert hanglted to pots, SUUTR is mumgaized by Ribmont fe fale tearalelan, OTR Ts itr fer rat PoP Soe erate Regulation of gene expression "promoter Site where RNA polymerase Mf and multiple Promoter mutation commonly results in + feral tanscuipin $404% | other transcription factors bind to DNA dramatic LinJevel of gene transcription Hite tector aca msg Geta) GeiT te! Precis upstream from gene locus (rich upstream sequence with TATA and CAAT boxes) Enhancer DNA locus where regulatory proteins Enhancers and silencers may be located close to, ane Bete ian iyators”) bind, increasing expression of a far from, or even within (in an intron) fhe gene 1e on the same chromosome. whose expression they regulate. Silencer NA locus where regulatory proteins Tees cxogenas nn SiR sors") bind, deereasing expression of a cone on the same chromosome. crue TTaaninator:< Terminator segues fn bectesin cause £0 10 font Holrte sont and tap st ILS thot texutete tandenien RNA processing Initial transcript is called heterogeneous nuclear mRNA is transported out of nucleus to be (eukaryotes) RNA (hnRNA), hnRNA is then modified and translated in eytosol becomes mRNA. mRNA quality control occurs at eytoplasmie ‘The following processes occurin the nucleus: processing bodies (P:bodies), which contain * Capping of end (addition of cxonuecleases, decapping enzymes, and F-amethylguanosine cap)» Coverteretial Pmt’ nicroRNAs; mRNAs may be degraded or ~ Polyadenylation of 3 end (= 200 As) stored in P-bodies for future translation. => Splicing out of introns #y S084 Poly-A polymerase does not sequire.a template. Ee Capped, tailed, and spliced transcripts called mRNA, Sa ode s Scanned with CamScannerfor intton ok rans Tenn” ney repureRho($) fe. RNA polymerases Eukaryotes akes tRNA, the most 1,1, and I] are numbered in the same order common (rampant) type; present only in that their products are used in protein nucleolus. synthesis: FRNA, mRNA, then tRNA. RNA polymerase makes mRNA (massive), ‘-amanitin, foun microRNA (miRNA), and small nuclear RNA cap mushrooms), inhi (snRNA). ‘Causes severe hepatotoxicity if ingested. RNA polymerase llfmakes 5S.4RNA, RNA Actinomycin.D, also called dactinomyein, (tiny). inhibits RNA polymerase in both prokaryotes No proofreading function, but can initiate and eukaryotes y big te OM chains. RNA polymerase II opens DNA at ‘Shiga tenn hls 28s of 68 promoter site, ™®YA ard ENA made in Exdromal Prokaryotes 1 RNA polymerase (multisubunit complex) Rifampin inhibits DNA-dependent RNA. ‘makes all 3 kinds of RNA. polymerase in prokaryotes. Splicing of pre-mRNA Part of process by which precursor mRNA (pre-mRNA) is transformed into.mature mRNA. Alterations.in snRNP assembly can cause clinical disease; eg, in RNP nara ' + ¢8, in spinal.muscularatzophy, snl onan 9 ste assembly is affected due to § SMNpssicin -+ congenital degeneration. of anterior horns of spinal ord ~ gymctaiseakness(hypotrie, ot “opp baby syndrome”) Tenge te” Primary vans cnines ith smarts roonoeepatea ists ane ter protest form spliceasome, Cleavage t 5 spice sitet staped (cop intermediates generated ~ Clevape at ste te: trat Mature mBNA Seated pecs remove inronandjin exons = gaan aay TM a a te Tat AR ine arBad is. D} helps 40 trensport mRNA (for trarbculption) ffm Nucleus %o Wy Changed OWA pao tl Wings eT i ane Manat args a4 of peas pace oper ea eae ane cpm eee ce e Scanned with CamScannerIntrons vs exons | BXGiis contain the. Achal GBAic information — Inte coding for protein sare intervening sequences and stay in the nucleus, whercas exons exit and are expressed. requently combined by © splicing to produce a larger number of unique proteins. er ee Alternative splicing can produce a variety of protein products froma single hnRNA sequence (¢g, transmembrane vs secreted Ig, {tropomyosin variants in muscle, dopamine receptors in the brain), im seit thts ses, [ses | ma A : Cn a — Ee ee ee rT ~ & & ®. a Tag compara of thas of AA band tegeiia, rgd Zine stow vie Uninge ¢ pteine “Fey em OMA binding demain - © ae trgen pra eran gO eo th es Vigna Coes A tl Reet Se Sos ST Cea gh hed hms of IEE geet sng “henge ptavia Aacepler. Binds vae., Te" velate om Ot, Lexenation ; Tostecblast stimulating Preesteoclart Aitfesubiahion he [ ter: Sinks eR Uatineld X receptor) as grat reguiler in many cals Aaa see eee aGensth and atfferentiation of many cells. &g-ATRA I A Retna [Retinal Receptors = Binds j i oe BoB euien Be many genes in Up and och mates By. Rte (PAR x), Tee CPPARAT) NprPaR Tie inde rae » Gis Ont — Po oe Disc ie ae ent badrg nmin) ret om eas Stel, Besa ee ee wr eh nde 1 cn a cn) ao anh ays for many ein tds aA (Tint L-¢, TEN, Prolachn, Mest tegred®. Banca Si Me RES arr ate an, tr dele eee et ae at GB Pans, sete Hadgehegs HOGER > Scanned with CamScannertRNA i Structure 75-90 nucleotides, 2° structure, clover anticodon end is opposite weylend. AN tRNAs, both eukaryotic and prokaryotic, have CCA aL3" end along with a high percentage of chemically modified bases. The amino acid is covalently bound tg the, end of the RIA Coa Can Carry Amino acids. %EEAisily tin solecna: © pet {ESEH: contains the TC (ribothymidine, pseudouridine, cytidine) sequence necessary for tRNA- ribosome,binding, T-arm Tethers RNA molecule to ribosome. Daim: contains Dihydrouridine residues necessary for tRNA. recognition by.the.correct aminoacyl- tRNA synthetase. D-arm allows Detection of the RNA by aminoacyl-tRNA synthetase. -Attachmentsite: the 5-CGA3" is the amino acid acceptorsite Charging ‘AminoacyltRNA synthetase (uses ATP; | unique enzyme per respective amino acid) and binding of charged tRNA to the codon are responsible for the accur uct ang acid selection. Aminoacyl-tRINA synthetase: matches.an.aminoacid to the RNA by. S@AUSTZNE the amino acid before and after it binds to tRNA. If an incorrect amino acid is attached, the bond is hydrolyzed. A mischarged tRNA reads the usual codon but inserts the wrong amino acid. & As ty Con ee Mates No Pairing Structure Charging {aminoacylation} (codon-anticodon) “ina 3c “y oy n H pee AIP ANPEPR, Fema” Ges 5 syatnetae 6 Avicodon (5-CAU-5 -C as position ‘mRNA MMU ANDAMAN Colon (5-AUG-3) Start and stop codons MRNAstartcodons AUG (or rarely GUG). AUG inAUGurates protein synthesis, Eukaryotes Codes for methionine, which may be removed ee before translation is completed. a __Prokaryotes Codes for N-formylmethionine (fMet). £Met stimulates.neutrophil chemotaxis. UGA,.UAA,.UAG. UGA = U Go Away. UAA =U Are Away. UAG =U Are Gone. TAPAS TR eA ar om iden tok clemnlaf shar. bu oon tke ain tape Scanned with CamScannerNSH i = . Mo ace initiation factor (el) identify ukaryotes 408 + 60S = 80S (Even). Sree Prokaryotes: 308 + 50S = 70S (Prime). + ell’ help assemble the 40S ribosomal : y ribosomal nl from N-terminus to subunit with the initiator tRNA, reemeu termini elf released when the mRNA and the i bosomal 608 subunitassemble with the ALP-—#RNA Actsation (charging), complex, Requires C11 GIP—tRNA Gripping and Going places @ aminoacyl-tRNA binds to site (except for msloction). inWator methionine, which binds the P site, ‘Think of “going APE": && t #- Tequires an elongation factor and GTP. Asite = incoming AminoacyltRNA. @ RNA (tidorsine" catalyzes peptide bond ste = accommodates growing Peptide. formation, transfers growing polypeptide to _-Esite= holds Empty INA as it Exits amino acid in A site. @Ribosome advances 3 nucleo 7 ye ence 5 6c Ree a ‘eotides toward 3” ee NGR ca aa -end of mRNA, moving peptidyl tRI ae gee vesmadta. » moving peptidyl tRINA to P ie Thaw big 20 “site (translocation an eaten eanee'® alamnde, Tofesmadin sure 2 ate Eukaryotic release factors (eRFS) recognize the Shine fet Gaane Aemuerce » 16s reNA te entpaale Mee (oe Ghent te rine del QRine stop codon and halt translation ~ completed Tose, et since Ritoneme Binding: polypeptide is released from ribosome. Requires GTP, ‘Sal Sitmal ls (3688). nds mth Caading frame) ak — caer ends £W0A nee) ye nibeoral Sibu (See, 4e4) Contains pertdyttranafeinue Btn Sialyees uptite bend (ore? belween 8 Intstce @ rans Ee vie : \exera \ Elongation ay {or C-terminal propeptides from zymogen to generate mature protein (€g, trypsinogen to trypsin). Hertons, Fl aptonincy ermine, brim lation, methylation, acetylation, and ubiquitina Scanned with CamScanner“Checkpoints control transitions between phases of cell eye ‘cyclin-dependent kinases (CDK9), and tumor suppressors. ilaphase, anaphase, includes mitosis (prophase, prometaphase, le. This process M phase (shortest phase of cell cycl {elophase) and cytokinesis {cytoplasm splits in two). Gy and Gy ate of variable duration. Constitatively expressed but inactive when not Coa hte by pad ren hence bound to cyclin. “rribing as pho Regulatory proteins that control cell cycle events; phase specific; activate CDKs. Phosphorylate other pldteins to coordinate cell cycle progression; must be activated and inactivated at appropriate times for cell cycle to progress (p53 = p2l induction + CDK inhibition + Rb Lypophosphorslation (activation) + GS progression inhibition. Mutations in tumor suppressor genes can result in unrestrained cell division (eg, biskraumeni syndrome)-$844 Growth factors (eg, insulin, PDGF. EPO, EGI bind tyrosine kinase receptors to ; cell from G, to S phase Enter @ from @o when stimulsted ‘Never goto Ge, divide rapidly with a short Cy Most affected by chemotherapy. Site of synthesis of secretory (exported) proteins nc. _ ad of Noinked oligosaccharide addition to gh aprons lysosomal and other proteins, _Nissl bodies (RER in neurons)—synthesize “, p55 modulate G,restcton pint 1s, skeletal and cardiac mustle, RBOs Hepatocytes, lymphocytes, BCT, periosteal cells: Bone marrow, gut epithelium, skin, hair follicles, germ cells Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are tich in RER. Proteins within organelles (eg, ER, Golgi bod lysosomes) are formed in RER.(Atached Rikoaa FP RER« t pron Sythe prema cna Pens) Scanned with CamScannerSeer for i i proteins and fj CR Posttranslational events in, Golgi include Gene Sic se ted fone z ‘on serine and threonine, and adding mannose-6-phosphate to proteins fo ng centets for material from outside the cell or from the Golgi, sending it to |ysosomes for destruction or back to the membrane/Golgi for Further use. ‘Weel dis@ase (inclusion cell diseasehmcolipid isorder m cell disease/mucolipidosis type Il) —inherited lysosomal storage disorder {autosomal recessive; defect in N-acetylghicosaminyl-L-phosphotransferase — failure ofthe Golgi to phosphorylate mannose residues (1 mannose-6-phosphate) on glycoproteins — proteins are secreted extracellulatly rather than delivered to lysosomes. RSUIG in coarse facial features, ginal per a, clouded corneas, restricted joint movements, law hand deformities, syphoscoliosis, c Often fatal in childhood. — il oye eae nama less of bamscml suave, Often lal ictal a en or pa SC ‘cytosolic ribonucleoprotein that Endosomes are so F Lraffies polypeptide-ribosome complex e from the cytosol.to the RER. Absentor a a i ees Mir, = X dysfunctional SRP — accumulation.of Qf ene ! ‘ > rercaase vos" 3a {GOPI:Golei = Golgi (etrograde);ci-Golgt BS icone | 1 ieee! —Q —GOPIK ER ~ cis- Golgi (anterograde) “Two (CPI steps forward (anterograde); one (COPI) step back (retrograde)” ‘rans.Golgi ~ Iysosomes; plasma ‘membrane -> endosomes (receptor . apporats fe Sep mediated endocytosis [eg, LDL receptor aa activity) endopiac 3 e In BR al in Fok focstins == Ginter oe Eat tal pron hem tse ces eoveope SS prgustn, Zen, eigen docant requre: Naber Membrane-enclosed organelle involved in: = oxidation ofvery-ong,chain fatty acids (VLCEA) Gtietly peroxisomal process) « qeoxidation of branched-chain fatty acids (strictly peroxisomal process) + ami and ethanol( te cian) + Synthesis of cholestrol, bile acids, and plasmalogens (important membrane phospholipid n) womal recessive disorder of peroxisome biogenesis due to Is, early death, ‘especially in (ne master) Zee syndome genes eateso) (Refsuim dis autosomal recessive disorder of a-oxidation - ph oe Boar inact S20 Skin, aaxi,eataractslnight blindness, shortening of th i st Treatment: diet, plasmapheresis. ser i sive disorder of B-oxidat Scanned with CamScannerme cases of 3 ary ovtet Poukneos Cytoskeletal elements A network of protein fibers within movement, and cell division, PREDOMINANT FUNCTION Muscle contraction, cytokinesis Maintain cell structure filaments Microtubules Movement, cell division Microtubule Positive ends) eosin A Gylindrical outer structure composed of a helical array of ed hete of @-and B-iubulin. Pach dimer has 2 GDR bound. ted into flagella, cilia, mitotic only, collapses quickly slow axoplasmnic transport in if Also inyo neurons. Molecular motor proteins —transport cellular cargo toward opposite ends of microtubule, © REtrograde to microtubule (+ + -)—DYnein * Anterograde fonicrotubule (~-+* +)—Kinesin. + Clostridium tetans, retrograde transport + Reoctivalion of Rormant Virus =| ims, ‘poliovirus, and rabies virus use dynein for ee Parkinson disease, A! 50 the eytoplasin that supports cell structure, cell and organelle NPL Actin, microvilli. Vimentin, desmin, cytokeratin, lamins, glial fibrillary acidie protein (GFAP), neurofilaments, Cilia, flagella, mitotic spindle, axonal trafficking, centrioles ‘Drugs that act on microtubules Microtubules Get Constructed Very Poorly) * Mebendazole (antihelminthic) * Griseofulvin (antifungal) * Colchicine fantigout) + Vincristine/Vinblastine (anticancer) * Paclitaxel (anticancer)~ pestis. Negative end Near Nucleus Positive end Points to Periphery. REaDY? Attack! yale arent maa Dajan Aranda unr re Scanned with CamScannerGilia structure Sedoublet+2 singlet arrangement of microtubules Basal body (base of cilium below cell membrane) consists of 9 microtubule Uwiplets 9 with no central microtubules ATPase that links peripheral 9,doublets and causes bending of itm by differential sliding of doublets. Gap junctions enable coordinated ciliary movement. Sodium-potassium Nat-K®ATBase is located in the plasma pump ine with ATP site on cytosolic side ATP consumed, 3 INa" Ieave the cell p phosphorylated) and 2 K° enter the mp dephosphorylated) Plasma membrane is an asymmetric lipid bilayer containing cholesterol, phospholipids, sphingolipids, glycolipids, and proteins. Extracellular 3Nat “0. space ‘s ot 99 peg” oC pam TION ei a membrane |) |) eee { sapanaaire Seg tip @ | Kartagener syndrome (1° ciliary dyskinesia) — immotile cilia due to a dynein.arm defect Festa areke: ‘Autosomal fecessive. Resulls in F myaleand sau wgatty female fertility due to immotile spetm and’ art dysfunctional fallopian tube cilia, respectively + risk of ectopic pregnancy. Can cause bronchiectasis, recurrent sinusitis, chronic car infections, eonductive hearing loss, and situs inversus (eg, dextrocardia on CXR f) 4 nasal nitric oxide (used as screening test) (Kartagener’s restaurant: take-out only; there's node ee es Pumpkin = pump K° in. ‘Ouabain (a cardiac glycoside) inhibits by binding to K° site Cardiac glycosides (digoximand digitoxin) dieetly inhibit the Na'-K ATPase, which leads to indirect inhibition of Na’/Ga®* exchange — t [Ca‘*], + t cardiac contractility ai are PARE Poy red a ae peri ncr, ya ea Scanned with CamScanneree tne hyaline), vitreous body, - ae eel lamina), lens ermal Sptiearel yunclon, Plaseta, Aabiumtne Lang yeragid foe and structure ‘Type IV: under the floor (basement membre Defective in Alport syndrome; targeted by autoantibodies in Goodpasture syndrome. Classe ener Sanles (Tepe 2) @ synthesis—translation of collagen a chains © Preprocoagen 7 0 Prectan nnn tan Homo of pain and e Lay Iyer vam oy ~~ oby Sugar YN Ocoee ot Cleavage of procollagen ese Paoullagen Pepidate (preprocollagen)—usually Gly X<¥ (X and. Y are proline or lysine). Collagen is glycine; glycine content of collagen is less variable than that of lysine and proline. of collagen. @ Hydroxylation— hydroxylation of: specific proline and lysine residues. Requires vitamin G; deficiency > scurvy. © Glycosylation—glycosylation of pro-o-chain hydroxglysin residues and formation of procollagen via Problems forming triple helix — os imperfecta. Exocytosis—exocytosis of procollagen into extracellular space. . dlisulfide-rich terminal regions ~ insoluble tropocollag Scanned with CamScannerOsteogenesis imperfecta enelie bone disorder (brittle bone disease) caused by a variety of gene defects (inost commonly COLIAL and COLIA2). Most common form is autosomal dominant With # production of otherwise normal typelL collagen. Manifestations include * Mollipe ictre and bone deformities afte * Bluesclerae E¥due tothe transtn connective tissue over choroidal veins + Some forms have tooth abnormalities, including opalescent teth that wear easily duc to lack of dentin (dentinogenesis imperfecta) + Conductive TE Asp cohesperessede bone density Mentoring LATTES uy Gon be ARO well whTch ually Gore have mid In CLLAL ard ee LtAD Ehlers-Danlos Faulty collagen synthesis causing i byt Snares and tendency to bleed (easy bruising) Multiple types. Inheritance and severity vary Can be autosomal dominant or recessive. May be associated with joint dislocation, berry.and. rela aortic aneurysms, organ rupture, Hypermobility.type (joint instability): mos ‘common type. “ster Classical type (joint and skin sympioms} ‘caused by a mutation in.type V-collagen (eB, COLSAI, COLSA2). Vasculantype (Fragile tis {eg, aorta, muscles, and organs tha to rupture [eg, gravid tera]: mutations 2 type ll procollagen sues including vessels (eg, COL3AD). « caused by impaired copper abs ‘is ATPIB in Wilson disease). Low copp' \ysyl oxidase (copper is anes hair, growth.setardation, hypotonic Xelinked recessive connective tissue di “Ine to defective Menkes protein (ATP2A, Jevels in Wilson disease). Leads be a is Peete collagen. Results in brittle, “kink aneurysms. Menkes disease mal trauma (eg, during birth)- * deter Osea ing loss (abnormal ossicles) susie sin E, hypermail joints EX {tare prone May be confused with child abuse. ‘Treat with bisphosphonates to 4. fracture.risk Patients can't BITE: Bones = multiple fractures I (eye) = blue sclerae Teeth = dental imperfections Ear = hearing loss sorption and transport er levels (vs high cessaty cofactor) * “brisk of cerebral Scanned with CamScannerElastin Stretchy protein within skin, lungs, large arteries, clastic ligaments, vocal cords, ligamenta flava (connect vertebrae -+ relaxed and stretched conformations). <. Dy» Rich in nonhydroxylated proline, glycine, and lysine residues, vs the hydroxylated residues of collagen. Ne Sig tok ge, Ne hynensin 1 Gieznylhion, Sexe ‘Tropoelastin with fibrillin scaffolding. lain soe ‘Cross-linking takes place extracellularly and gives elastin its elastic properties. Broken down by-elastase, which is normally inhibited by oy-antitrypsin. 4-Antitrypsin deficiency results in unopposed elastase activity, which can cause COPD. @ (Changes with aging’ 4 dermal collagen and elastin, # synthesis of collagen fibrils; cross-linking temains normal. Marfan syndrome—autosomal dominant (with variable expression) conncetive tissue disorder affecting skeleton, heart, and eyes. FBNI gene mutation on chromosoyne, 15 (fifteen) result defective fibrilliy, a glycoprotein that forms a sheath around elastin, aa an with long extremities; pectus carinatum (more specific) or pectus excavatum By; hypermobile joints; long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta; aortic root aneurysm rupture or dissection (most common cause of death); mitral valve prolapse. Subluxation of lenses, typically upward and temporally @@ downward and medially in homocystinuria), wmnerstinusth ise Tested by Adam Forced Tet rieaibead desi ECHNIQUES: Polymerase chain Molecular biology lab procedure used to amplify a desired fragment of DNA. Useful as a diagnostic. reaction tool (eg, neonatal, HIY, herpes encephalitis), «ute 5 5 5 a 5 5 sf DNA primer. i 5 oN ‘werrerennn — @ e aN pause x so 8 Repeat 5 Dowble-svanded DNA es ‘aan, — Taannnn, — SETI —~ igen of nA ri, 5 5 5 : moy eos a © Denaturation—DNA is heated to ~95°C to separate the strands, © Annealing—Sample is cooled to ~55°C, DNA primets, a heat-stable Dy ple is .c.0 a heats INA polymerase (Tag), and deoxynucleotide.riphosnhates (ANE are added, DNA primers anneal tothe specie sequence to be amplified on each strand. © Elongation—Temperature is increased to ~72°C, DNA strand to replicate the sequence after each primer, Polymerase attaches ANTPs to the Heating and cooling eyeles continue until the DNA sample size is sufficient. ‘en leverse transcriptase Detects and quantifies mRNA | na staand levels ina sample, Uses reverse transeript jolymerase:chain complementary DNA template that is amplified vin standard POR neon rete a Sonplepepian DNA empl lat amplified vig standard PCR procedne . eerie from ROA SAR futin fe Cote» es Scanned with CamScannerUST 7 7 Redaete Dequence = 4 STRUTT er? " ere Ren) dene a RTS tral aa inet yacht gS 4 AAR oF ein fe OS 4 Raa tein) CRISPR/Cas9 A genome edit ing tool derived from baeteria. Cx complementary ton target DNA ve Consists of a guide RNA‘ i Sela fo arBeL DNA sequence and an endoncense (Cas) on ania sas anal beak a the get site @. Break imperfectly repai oly logue inning ut = eee imeshift muta jos (hock) ©, ors don Ne Not used clinically. Teall heh D0 Se - al applications include temov dineasccasingallde of gene eit as and pe civtnstngtamees hy variants, and spy , "Bie Pine copes ented by Gene. Tarogy- Viral Cesaceakis seaged expen [oat expmson eve Te nego i ee reat ate (lk of Brest Lege et Ov, (argo) EMA ye sue ree ‘igo ct) ee ee reheat) wad mati re EL ea at eng rae Men pas th cn ake fect neping ate Mt 2 ee ea oS rere SESE are’ eventualy foot = Peer machina meget perro Rote Virus + Thaarh thelr Anrense ‘parscbed O44 mmr ah Be a en TY nig Py cece EN Bhagat wed © 1 0 me , of evinces Ged Tn ii Se Satna ominge Cat th ol Fam Sn ee eimgimaat atom "Oman a ; ral Vcc gs Umer Wh cn in gdengig an Blotting procedures Southern blot 1. DNA sample is enzymatically cleaved into + For Gene. Reamangement? smaller pieces, which are separated.on.agel oe “ by electrophoresis, and then transfreed toa | Oe. ane SE pnaygia of Ungh of filter. fregmants of gene by 12, Filter is exposed to radiolabeled DNA ivecnen wee robe that recognizes and anneals to its patate ta! Aner probe that recognizes and annea ‘complementary strand. 3, Resulting double-stranded, labeled piece of DNA is visualized when filter is exposed to film, Similar to Souther blot, except that an RNA sample is electrophoresed. Useful for studying MARNA levels, which are gefletive of gene expression. RNA Western blot Sample proteit iesepaated vin gel eletrophores—Wesory = Protein vind transferred toa membrane. Lae ‘antibody is used to bind tosclevat prot Southwestern blot Identifies DNA-binding Drm (5 ohm, “eLfos [leucine zinper motif) using nbc’ J probes: hele Jee fy le-stranded NA double standed DNA prt le SouTveme oT erm gre eget a aed ERA A oy Sino " eee tee Northern blot DNA Scanned with CamScannerTinton hgghtnatin eats Check —caadan Aaitedy_ ond Patgens ee Aaaletiain Tet» ST mi Atal fe mehingsmna Flow cytometry Laboratory: and protein expression (immunophenotype) of individual cells in a, fetal RBCs jn 3 and TOT Av il immunodeficiencies ee ells C Sa CD#* cell count in HIV). . Cells are tagged wit Auorscent surface or intracella be q are then tagged with a unique fl Antivody- te dye, Sample is analyzed one cell at atime by . focusing a lascr on the cell and measuring ‘AnU-CDS Ab Sa light seatter and intensity of fluorescence. oiscOB A 7 Fcrescenee ”] ‘edeectes. Wy oiedcels GO recounted \ Data ae plotted either as histogram (one ‘meastte) or scatter plot (any two measures, as shown). In illustration: * Calls in left lower 4 and CDS. * Calls in right lower quad \drant © for both CD8. © for CD8 and © for CD3. In this example, right lower quadrant is emply because all CDS -expressing cells also express CDS. + Calls in left upper quadrant ® for CD3 and © for C8. *+ Cells in right upper quadrant ® for both CD8 and CDs. Microarrays ‘Thousands of nuclefe acid sequences are arranged in grids on glass or silicon, DNA or fA probes are hybridized to the chip, wer detects the relative amounts of complementary binding. Used to profile gene expression Jevels of thousands of genes simultaneously to study certait: diseases and treatments. Able fo deleet single nucleotide polymorphisms (SNPs) and copy numbex cluding genotyping, clinical genetic testing, ashy aaron) fizymestnked Immunologic test used to detect the presence of cither.a specific anit entibyina pai at's nesorbentassay blood sainple. Detection inwolves the use of an antibody linked to an enzyme, Added substrate ne, producing a detectable signal. Can have high sen: less specific than Western blot, Hiv p 24 Ag debestion via Kondwith 35h: 2 BS oscil than Western Hot Es a As aoe Yenct LUSH ALT Faken Tobe tented Banas ial pIGFE= Aigan emaned te Bona ; Tas aS FOF F take, sath wamy FAT oo Upbsled Ab) srzidhe to ag" rbaah ascart Unboned he hang subsbole ghee colar Daoged Dyacc ag RE Tindireot ELLA 1 Ad danunt for aralys (Uke is), Add Ab te My of Intent: (Ab anetengyne tnt): ta, assy worbaund A Tapa bay pe baking tian pret Fe Semple Nina add ergy Sebeedeerdaly “Al thy Birds bes AL, Aad auhoprale, © Coler charge —> Ldenbifcr ef Ay In serurns Gray Hip Ab trcioclly binds A ty and specificity, but is Scanned with CamScannerPIC Golehicine i added to cultured cells to halt ‘hvomosomes in metaphase. Chromosomes are tained, ordered, and numbered according to morphology, size, arm-length ratio, and rows in EY point to exter +d on a sample of blood, bone cow, amniotic fluid, or placental tissue. Used to diagnose chromosomal imbalances tosomnal trisomies, sex chromosome Fluorescent DNA or RNA probe binds to specifi gene sit of interest on chromosomes {Grows in BY point to abnormalities in a cancer cell whose karyotype is seen aboxe; each Auorescent color represents. a chromosome- specific probe). dan 6 don nhl pee Used for specific localization of genes and direct visualization of chromosomal anomalies at the molecular level * Microdeletion—no fluorescence on a cliromosome compared to fluorescence at the same locus on the second copy ofthat homosome. + Translocation—Aluotescence signal that corresponds o one chromosome is found in a different chromosome {two white arows in BY show fragments of chromosome 17 that have translocated to chromosome 19) * Duplication—a second copy ofa, chromosome, resulting in a tison tetrasomy (two blue arrows show dy chromosome 8, resulting Fluorescencein situ “hybridization Molecular cloning Checders of Ves ty =. SIDS Production of a recombinant DNA molecule in a bacterial host. ning Redraien faguets> 1. Isolate eukaryotic mRNA (post RNA processing) of interest. Rand 2. Add reverse transcriptase (an RNA-dependent DNA polymerase) to produce complementary OUP Rar wane kaatns) DNA (CDNA, lacks introns “Transform (inset Insert DNA fragments into bacterial plasmids containing antibiotic resistance genes. nbfnant plasmid into bacteria Surviving bacteria on antibiotic medium produce cloned DNA (copies of cDNA), Radtotwnmoasagy + lb Fedviqe Bat wee ‘ana of anion Proert hah fg ant neactithy measured Ratna No change tn Antone wile ‘Yaniger me” ao. ne shod BE APTS: Sra iC Abe and a Fron auanlly of Radiolabcled aubger to datowume the Sample Specie Als agetnsh’ Kineust ankigen etfached to casey plate. Next: Grad ancunt of Atalolabwled Ay ard varying quanthes ey Urlabled Af added: Tan f washed to tn nactoacnsy % TY come pe Meat stare game. epics Ord omy ‘quali’ for Ae bang A> Grey Scanned with CamScanner0 mB 1 Siete DOES Lis PB gen = Nothing happened: A Gene expression ‘Transgenic strategies in mice involve: | modifications + Random insertion of gene into mouse Kno inserting a gene. f genome: * Targeted insertion or deletion of gene Random insertion—constilulive expression. 1 & i : through homologous recombination with ‘Targeted insertion—conditional expression 1 mouse gene j Cre-lox system ‘Can inducibly manipulate genes at specific developmental points (cg, to study a gene whose | i deletion causes embryonic death), | i RNA interference Process whereby small non-coding RNA molecules target mRNAs to inhibitgene expression. | to MiccoRNA(IRNA) Naturally produced by the cells hairpin [Abnormal expression of miRNAs contributes | im in Aucional deviant de structures, Loose nticleotidle pairing allows to certain malignancies (cg, by silencing an | } broader targeting of related mRNAs, mRNA from a tumor suppressor gene) { Mocking tansation and secceratng RNA | : degradation, (Gxdagenas ailenceg), | Smallinterfering Usually derived from exogenous dsRNA source Can be produced by invitto transcription for | RNA (SIRNA) (cg, virus). Once inside a cell, RNA requires gene “knockdown’ experiments. | complete nucleotide pairing, leading to highly. } specific MRNA targeting. Results in mRNA | cleavage prior to translation. te Gere mincing (beageneu) | TR ERS BAS TE ET - | | i | | Genetic terms 7 | ia ann ‘an 7 | : Codominance Botl alleles contribute to the phenolype of the Blood groups A, B, AB; ayantittypsin | i heterozygote. deficiency; HLA groups. | _Natlableexpressivity Patients with the sae genotype have varying 2 patients with neurofibromatosis ype (NFU, oa: Reh te” phenotypes ‘may have varying disease severity ‘Incomplete Not all individuals with a mutant genotype BRCAL gene mutations do not always result in penetrance show the mutant phenotype. breast oF ovarian eancer % penetrance x probability of inheriting sgenolype = fifk of expressing phenotype (PKU) manifests with Untreated phenylketo ‘ y, and musty body light skin, intllee odor; Mages jer,0x “Trimucleotide repeat diseases (eg, Huntington disease), inhetits or develops a mutation in @ tumor suppressor gene, the complementary allele mut be deleted/imutated before cancer deyelops, This is not true of oncogenes ‘5 Hetero 7 inMatt fed ence ve nih, € nuchition aich dict Thy gene exprsiton 4 in ewpertmental group? ei rn i rt, me dye ° | eromon {which lle of Cre gece affects phordhyle Cxpmauen of alleles tn arslher gene | Eptaiae» Scanned with CamScannerGenetic terms (continued) Tea eon URE } Dominant negative Excris a dominant effect. A heterozygote “Assingle mutated p53 tumor suppressor gene mutation produces a nonfunctional altered protcin that results in a protein that is able to bind DNA and } also prevents the norinal gene product fiom _ block the nonmutated p§3 from binding to the | functioning promoter. Linkage “Tendency for certain alleles at 2 linked disequil loci to occur together more or ess often than expected by chance. Measured in a Population, notin a family, and offen varies in different populatios Presence of genetically same individual ‘Somatic mosaicism—mutation arises from ‘mitotic errors after fertilization and propagates through multiple tissues or organs. Gonaidal mosaicism—mutation only in egg or sperm cells. If parents and relatives do not ease, suspect gonadal (or germline) inct cell lines in the ions at different loci ean produce a similar phenotype. Locusheterogeneity ee ome gone Se te Allelic heterogeneity JdeoNlopin genes =» Bgl Jovan. it mutations in the same locus produce the same phenotype. Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease. Uniparentaldisomy Offspring receives 2 copies of « chromosome from Sr ath end ue 1 parent and no copes from the other parent. Meter: 4¢ and 210: affcoiions trong) indicates a meiosis [fc Aks Tene = ama Seem ™Tertor, lsodlsomy (homozygous indicates + C0 stetaedoony = 2 rtm.” meiosis ll error or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the other of the original pait. Heteroplasmy se urs tbh test ae it McCune-Albright syndrome —duc to Grprotcin (od. | ‘activating mutation, Presents with’nilateral STCSUTRT pots BY with ragged edges,(omtotMamd polyostotic fibrous dysplasia (bone is replaced by collagen and fibroblasts[“and at least one endocrinopathy (eg, precocious puberty)ar Spay Lethal if mutation occurs before fertilization (affecting all cells), but survivable in patients ‘with mosaicism epraae ue) Awe 0 Buthalassemia. mtDNA passed from mother to all children. Uniparental is euploid (correct number of chromosomes). Most occurrences of uniparental disomy (UPD) ~ normal phenotype. Consider isodisomy in an individual manifesting a _recessive disorder when only one parent is a carrier. ExanipleS Pradec Willi and Angelman syndromes, Complete, “Ae- _ Hardy-Weinberg Population genetics fp and q represent the frequencies of alleles ‘Nand, respectively, in a population, then pack rT vol 7 wr ‘oa ma | a a0) og |e feequeney, ‘Therefore, the sum of the frequencies ofthese genotypesis p? + 2pq + 4? = 1 ‘The frequency of an X-linked ffecessive disease Hardy-Weinberg law assumptions include: * No mutation occurring at the locus * Natural selectio + Completely random mating, * No net migration * Large population Ifa population isin Hardy-Weinberg ‘equilibrium, then the values of p and q remain constant from generation to generation. ae Ne true fen maton canes “Qarieees 1 we To pechae ef Dene = Tait Scanned with CamScannerDisorders of miprinting’ Imprinting—one = parent-of-ori Prader-Willi syndrome ‘AngelMan syndrome WHC NES SENT Maternally derived Paternally derived UBE3A is silenced Disease occurs when the Paternal allele isdeleted Disease occurs when the Maternal allele is deleted or mutated (or mutated ‘seus ano svurrous Hyperphagia, obesity, intellectual disability, Seizures, Ataxia, severe Intellectual disability, ‘CHROMOSOMES VOLVED Chromosome 15 of paternal origin UBE3A on matemal copy of chromosome 15 ones 25% of cases are duc to maternal uniparental _5% of cases are due to paternal uniparental disomy disomy Prader has no Dad (Paternal Deletion) MDs are angels (Maternal Deletion) es 2 Scanned with CamScannerModes of inheritance 7 ‘Autosomal dominant Often duc to defeets in structural genes. Many Often pleiotropic (multiple apparently unrelated generations, both males and fernales are affected. _ effects) and variably expressive (different far between individual), Family history crucial ; B to diagnosis. With one affected (heterozygous) & parent, on average, % of children affected. .: With 2 carrier (heterozygous) parents, on average: Often due to enzyme deficiencies. Usually seen 4% ofchildeen will be affected (homozygous), _in only I generation. Commonly more severe % of children will be carriers, and % of than dominant disorders; patients often present chil wer affected nor carriers. __in childhood. Aa {risk in consanguineous families. Jnaffected individual with affected sibling has a A gag a 2B probability of being a carrier. P %linked recessive ‘Sons of heterozygous mothers have a 50% ~ Commonly more severe in males. Females chance of being affected. No male-to-male _usually must be homozygous to be affected. 4 ler | transmission. Skips generations. x ox x x x mm Km x « ‘Transmitted through both parents. Mothers transmit to 50% of daughters and sons; fathers toaall daughters but no sons. 1, Alport syndrome, Ga {also called Xlinked scimal tubule ~ rickets-like presentation, Cormuety yon uty) Re 7 rept (chan gr 23Qenpmatel in Bore = meee S ca Yow rm ‘Transmitted only through the mother. All Mitochondrial myopathies—rare disorders; offspring of affected females may show signs of often present with myopathy, lactic acidosis, disease. and CNS disexse, eg, MELAS syndrome Variable expression ina population or even (itochondyiaencephalomyopathy, lactic within a family due to heteroplasmy. acidosis indtvoke-ike episodes). 2° to MERE (yedoe tits Red mage ibm fed)» failure in oxidative phosphorylation Muscle q beat biopsy often shows “tagged red fibers” @ue to FI syeias = eRWA Lysine dafechs 5 accumulation of diseased mitochondria in the saad eet subsarcolemma of the muscle fiber. Leber hereditary optic neuropathy-cell q death in optic nerve neurons ~ subacute rales, Usually permanent. T)-woteced male; [teed ma: Q)=wnatecederae: @=ateced tee 4 Polygente Grhedtanca p Many Woltslay depend on malin genes, Bp. Wadroganle Alapasin, Eplemsy, Glancora, HON, CAS, Gohiaay Mulljactortal Zbessenca so Geos Liaagetntrorment= Sense: Sean Im Yoni x By Bion, Okey pl py Ele pate Scanned with CamScannerAutosomal dominant diseases onsinant polyystic kidney disc hypercholesterolemia, hereditary hemorrhagic telangiecta syndrome), hereditary spherocytosis, Huntington disease, | syndrome, Marfan syndrome, multiple endocrine neoplasias, myotonic museular dystrophy, neurofibromatosis type 1 (von Recklinghausen disease), ncurofibromatosis type 2, tuberous sclerosis, von Hippel-Linelau disease, lial adenomatous polyposis, (Oster Weber Rendit Autosomal fecessive diseases recessive polycystic kidney disease (ARPKD), eystic glycogen storage diseases, mucopolysaccharidoses (except Hunter syndrome) sphingolipidoses (except Fabry disease), thalassem wemochromaloss, Kartage ylketonura, sickle cell PaTHoPnioUaGy across courucanions mestwext Cystic fibrosis ‘cenencs Autosomal recessive; defect in CFTR gene on chromosome 7c a deletion of P08, ‘Most common lethal genetic disease in Caucasian population. Staret pete jeding ant the CETR encodes an ATP-gated Cl channel that scerctes Cl in lungs and G1 tract, and reabsorbs, ‘Cl- in sweat glands, Most common mutation = misfolded protein ~ protein retained in RER and nol transported to cell membrane, eausing | CI (and H,0) secretion; 1 intracellular Cl results in compensatory 1 Na" reabsorption els (ENaC) ~ 1 H,0 reabsoxption = abnormally thick mucus seereted into hangs and Gl tract. 1 Na’ reabsorption also causes more I potential difference.» t= r= iu OR mane sual thay duced sweat tes is di effects analogous to a ps tic. Can present with contraction isand hypokalemia (ECF nt taking a loop diuretic) becanse i (of ECF HO/Na'* Josses via sweating and concomitant renal K'/H* wasting. immunoreactive trypsinogen (newborn sereening). nme noe ‘Saaureus [infancy and early childhood], P aeruginosa or Stpsae spergillosis {ABPA), chronic bronchitis and {adulthood|, allergic bronchopu tasis ~ reliculonodular pattern sufficiency, malabsorption with steatorrhea, fat-soluble vitamin deficiencies (A, D, E, EteHMOSs, liver disease. Meconiuin ileus in newborns Wer srt) logenesis may be unaffected) and subfertility in. s clearance, " saiuomy PES ene replacement therapy frp | lh Phe508 deletion: c« of amacafior(oncels misfolded rotenteaad improves | spot to cell surface and incall (opens C- channels improved horde anspor | AY o Hon 9. CET a ation nl TOT Pada TE Has Paar ONE IOS CE A iim Scanned with CamScannerBIOCHEMISTRY Xlinked recessive disorders Ornithine transearbamylase deficiency, Fa disease, Wiskoll Aldrich syndrome, Ocular albin Braton agammaglobulinemia, Hemophilia Aand B, Lesch-Nyhan syndrome, Duchenne {Gnd Becker) muscular dysteophy. Xinactivation ion)—one copy le X chromosome forms a GGPD deficieney, Hunter syndrome, Females with Turner syndrome (45,XO) are more likely to have an X-linked recessive disorder. ‘Xlinked disorder typically due to frameshift deletions or nonsense mutations — truncated or absent dystrophin protein ~ progressive ‘myofiber damage, Weakness begins in pelvic girdle muscles and progresses superiorly. Pscudohypertrophy of calf muscles due to Sibrofty replace of muscle BY Wading Onset before 5 years of age. Dilated Cardiomyopathy is common cause of death uses upper extren help stand up. Classically seen in Duchenne ‘muscular dystrophy, but also seen in other ‘muscular dystrophies and inflammatory’ ‘yopathies (eg, polymyositis). Becker Xelinked disorder typically due to non feameshift deletions in dystrophin gene (partially functional instead of truncated) Less severe than Duchenne (Becker is better). Mvetonie dystrophy Autosomal dor Tyre expansion in the DMIPK gene ~ abnormal "Serer a ewe expen of motonin potin Kinase SETG Tetranieae rep ~ myotonia (cg, difficully.rcleasing hand, ‘rox handshake) imusele wasting, cataracts, testicular atrop! ee) x a a Onset in adolescence or early adulthood. offen auasive tel Soa, int. CTG trinucleotide repeat Cataracts, Toupee (early balding in men), Gonadal 21s Meg othnd Ye, 205 De frontal balding, arrhythmia, Duchenne = deleted dystrophin. Dystrophin gene (DMD) isthe largest protcin:coding human gene = t chance of spontaneous mutation. Dystrophin helps anchor muscle fibess, primarily in skeletal and cardiac muscle It he intracellular Cytoskeleton lactis ho te toners” proteins a- and B. Recut which are connected to the extracellular matrix (ECM), Loss of dystroy 1.GK and aldolase; genetic testing confirms degen BE PGRN mtn rds | ig art Y Ts nao ‘oan a Deletions can cause both Duchenne and Becker muscular dystrophies. % of cases have large deletions spanning one or more exons. atrophy. Hen Sheen affeial= rolled sha, Ung menses Ferma hy pepenen easteaane PF lyre, Tapas VReeine e Scanned with CamScanner