Untitled

• These notes cover various topics in genetics, including pharmacogenetics, tumors, prenatal diagnosis, phenotypic variability, patterns of inheritance, chromosomal disorders and techniques of genetic investigation.

Pharmacogenetics

• Coumadin (warfarin) inhibits the VKORC1 enzyme.
• CYP2C9 inactivates coumadin.
• Gene duplications have been found in NAT, GST, and CYP2A6 enzymes.
• CYP2D6 does not inactivate coumadin.
• The cytochrome p450 oxidoreductase (CYP450) system shows the greatest polymorphism.
• Adverse drug reactions (ADR) are unintended physiological responses to a drug that cause harm to the patient.
• Pharmacogenomics uses genomic information to design and test new medications.
• Technologies used in pharmacogenomic studies include proteomics, transcript analysis on a large scale, and metabolomics.
• The conjugation of a drug with glucuronic acid involves cytochrome P450.
• Individuals respond differently to the same drug dose due to genetic profiles, concurrent use of other drugs, and differences in body surface area.
• Allele, genotype, and phenotype frequencies in drug-metabolizing enzyme genes vary greatly among ethnic groups.
• Pharmacogenetics studies how genetic variability underlies differential drug responses.
• All listed factors are involved in the regulation of drug biotransformation reactions.
• Low activity of enzymes converting a drug into its bioactive form could reduce its efficacy.
• Pharmacogenetic tests can identify patients at greater risk of not responding to treatment or experiencing toxicity.
• Pharmacogenomics is not synonymous with pharmacogenetics, but rather applies systematic, large-scale approaches to discover genetic markers associated with differential drug responses.
• High activity of enzymes that convert a drug into its active form can enhance its action.
• Genetic markers studied in pharmacogenetics include all of the listed options.
• Pharmaceutical studies employ all the listed methods.
• Genetically polymorphic enzymes involved in drug metabolism include glutathione s-transferases, dihydropyrimidine dehydrogenase, NAT, and UDP.
• Individuals possess two copies of most genes involved in drug metabolism.
• Research in pharmacogenetics and pharmacogenomics has the potential to reduce healthcare costs.
• Pharmacogenetics studies atypical individual responses to drug administration due to genetic causes.
• Pharmacogenetics studies the genetic factors responsible for interindividual drug variation.
• Amylase does not intervene in phase two reactions
• Acetylation is a phase two reaction.
• Glutathione s-transferases are enzymes that participate in phase two reactions.
• Acetylation is not a phase one reaction.
• NAT2 inactivates isoniazid.

Tumors

• An oncogene is a gene involved in neoplastic transformation that promotes cell division.
• Heterozygosity for a BRCA1 gene mutation increases the risk of developing tumors.
• Cancer results from the activation of proto-oncogenes into oncogenes and the inactivation of tumor suppressor genes.
• Most breast tumors are not hereditary.
• RET (proto-oncogene) is not a tumor suppressor gene.
• Metastasis is the process by which a tumor spreads to distant sites.
• A tumor suppressor gene controls progression through the cell cycle.
• Loss of tumor suppression in a cell generally results from the deletion of a tumor suppressor gene.
• Angiogenesis is the growth of new blood vessels in a tumor.
• A chromosome deletion in a tumor genome likely affects a tumor suppressor gene.
• Complete elimination of the proto-oncogene is NOT a typical mechanism.
• Ion channel proteins are not generally encoded by an oncogene.
• A protein that inhibits apoptosis is not encoded by a tumor suppressor gene.
• Types of tumors present are rarely observed as sporadic tumors
• Tumor suppressor genes are often underexpressed in tumor cells
• Nonsense mutations that produce inactive proteins will not result in oncogenes
• Cancer is defined as a genetic disease because it is determined by genetic mutations on a somatic cell level
• Most tumors are caused by a series of genetic alterations.
• Oncogenes do not encode for: Rna polymerase Dna dependent
• Transfecting tumor cells cells expressing the version of an oncosuppressor will not result in neoplastic formation spontaneously
• Genes that normally impede cell division are: oncosoppressors
• Tumor suppressor genes encode all of the listed choices.
• BRCA1 and BRCA2 genes are implicated in hereditary breast and ovarian cancers.
• BRCA2 gene mutation on chromosome 13 predisposes individuals to breast cancer.
• Defective DNA damage repair mechanisms increase susceptibility to tumor formation.
• Patients with xeroderma pigmentosum have a particularly high risk of skin tumors.
• Patients defective in “mismatch repair" are at greater risk for colon cancer
• In hereditary tumors like retinoblastoma, there is a "germinal" mutation AND a “somatic“ mutation on an oncosuppressor gene
• Receptor with factor of growth is NOT gene oncosoppressors
• Genes inhibit the division of cells: oncosuppressors
• Wild-type genes that, when mutated, cause cancer are called oncosuppressors
• Loss of heterozygosity (LOH) is found where DNA loci encode oncosuppressors
• A proto-oncogene can become an oncogene through translocation near a transcription gene
• Oncogenes stimulate cell division
• Proto-oncogenes mechanism of action on somatic is dominant type
• Familial illness is dictated by protooncogenes
• A Protooncogene makes a gene that is involved in mecanhisms of cell growth
• Lymphoma cause the burkitt result by trnslocating a protoncogen which is located next to a gene for a immunoglobin
• Mutators do repair DNA
• APC is involved in colon cancer
• Instability of misrosatelites is a caracteristic of Heredity colon cancer not polyosis
• Gens that is involed in lynch is MSH2
• Protein that activity of of of lossing function generete mutations is called lofss of genetics
• Gains of Function: All the definitions are truee
• Lost function of genetics: produce phenotypes recesive Loss of the genetic functione: create hipomorfitcs or amorfts allels
• FGFR genes mutate in DISPLAISAS esqueleetricas reasul in gains function

Prenatal Diagnosis

• Prenatal diagnosis is indicated when the pregnant woman is 42 years old.

• Congenital malformations are more frequently multifactorial in nature.

• Neurological disorders can occur in achondroplasia due to stenosis of the foramen magnum.

• Autonomy: the concept that genetic counselling is of assistance

• Monosomy has the most drastic consequences.

• A phenotypically normal woman with t(21;21) translocation has a 100% chance of having a child with Down syndrome.

• NIPT is non invasive prenatal test.

• All the affirmations are correct about QF-PCR

• The exame of spontaneoous mitotics of amniocytes, does not exits, is only made after culture

• AFP, Estriol (Coniugate)and Beta-hCG are tested on the triple text

• PAPPA abd BetaHCG are tested in the Duo text

• Amniotic fluids in situ anñalisys is the analysis af at least 3 diferent culktures, 10 clonics or mores, 1 nice mitotis by clonic

• examning after culturing mitoics in villas corial: is executo on cells of mesoderm/stroma

• Examind directli mtotios in vialls corian: cells od citofoatobalsto

• most comum mtivoion to do genetic diahnis: big age

• verdadero mosaic (trhe lvl) in the aminocentesis is difinide by te 2 or mre anomalies coming from the difrente cvultivers

• the PRC can know monosmiias and trsonais for the cellsomnas is 13, 18, 21

• in men the presnce ofs tow masuvil prosnvcelss and with onee femiavnate, the celkks gets formaed by iones molicuals viscular

• the segenets does bot caiuse mutation is fr33 sinfrome wadernsbug

• fpr which does ot indicte caries in the epocao rneattal fibreiss cisca

• the prelvio of dlsquido aminito, e siqye poer la via percutna, es la semnan 107 Dal cariotype de una donna fenotipica, risulta portatrice de inversione, nel momento dellla dgravidanza l'esame del caritipo fetale Quando effetuare amniocentesi? Tra la dicessima sesdessima settimana di gestazione il termine congenito viene applicato di maltttie precentte del le cellule presenti del liquido ammiotici derivano tottue de le affermaioni sono vera tecnica diagnostiche diagnostica di di difetto nel burale a villi corali qual è di quelle errate? Test rapides sosttuiscino il materiale fecale Esistono test e screening sono genere sottpostti xchè è possibile che curable e prevenibili Quale di eseguenti nonei tecnica per diagnostiche rentale? Rahicentesi Quando si indentifica un musaismo per il cellsomnia 15 quali esesre persentte? Tottue le affermaioni sono correttee Qual è l'indicata, test del villaocentessi La frequenza di anamalibe cellsomixhe fra abortti spontanea e intorne al 50 per cento Il rischo di abortvita dopo anicentesiv e vulutato 100/200

Phenotypic Variability

• Phenotypic variability can be caused by genes and the environment.

• Relationship between heredity of multifactorial genetic variañciones

• Many genetics the variable phenotype in population

• Heredability estimates a proportion: variabilidiad en a grupo que puede atribuise a naturalezsa geentica

• Curved canampa in variable represent variations continues Qualche dissegneti nome esemplare di variazioni continues Queslltido de eridetataria de ilar una variazioni continues: porligenia

• are the only genetic factors and distinct result genetic and discrete : is result genetic

• cost of it is mappatura of loci that influençan quantitative? All the respots are corrette

• se toda la varaizan is of genetics cual is valoes: 1 Se la variable ambientali x caractererw3 y varianza feno totale 6 valor of charactere Se lo che la varaiznabef feno is vale y genetics Dipersione in tornado media in population: la veruianzsa charater queatitative varianzxa fenotyipic depende da some varianza gentettic ambiental

• valore de AS, il rapporsdtt de incidentes de ilarmatiad de

• is genttipus la varianza obsernveda is varianza ambientale Cual de la affemzione no correyt, por cada caratteres quw preseent diastribuzions normalen, el 99 porciento del loas inivduuos se collsca 2 desvcion standard Indica de le que patronmio qwe de le padres recibn

• qwe de le saiuazios meglio aralla la hipotesis qwe qenes son genetyicos

• thermin eeditbals is messur statystica el qrad of genetico

• coeficiente de disiqitico x el preoo corporalr and estado claculdsar 21. Cwal el eredibils de peo 042 El coeficiente de correlate entre gemilli monotigot x el peso stato caclulsat serer 042 Peso es una ejempla caracter quanittatois

• calcular irecticxo in el riecswo de reurrensica il reusita in icdienccia populd requiers la cogniccion de erediwbilidax Conve informa, por recierrcnxa esteonis pilorya, la forma de multifactors, con el moddelo a umvrale un alt x las fmeninas, the prdira irenciy de fmeninsis of problanbd

• il riscio di ricorrenzoza mqlfomazios conveienmte sur bas yiene calcu,adk nel seyente mode il bass empirica, uniliszar il labell,e ricavated de srydi di coppia che hnno avuto diverva cbmbnazionnidi figli, affetii csnil medisina condiuionw per cui viene recisdto de calcuwlae ild risxico.

• x termianet de qwe cdi a rapwro tre due variaobili cambio de una variable camioia aebil

• Un coeficiente de correlazionn de 1 indica: la coorelciinn diretttta perfetta

• suppoinamo che ibr coppue of alleles controllino le stutura nel ruino , senazade ffeties modificatorias ambientzalli, en equesreo simplie modello poligenico caisciuno alleee domiamnte controbutiscem12 cm ad in alitezsa bse de aliezsa 14 crm. Cuak ele il intervalo de variazio de los estadttos de la population: 144-214 cim

• Suppuoniamo che tre copule toalleles controlan la srtaira nel cuo.o seznza de offetis modificatorias ambiotall En queto suploicisdo modello poligenico , coiiscn alleele domionannte ciontribuce 12 cm ad un aliezsa base del atiezsa 14. Se uña donna della mniznma altezzam specie sposa un wimoo di alitezsr intermediatem cuall aloteza mzxima qwedrano rasggiungere u figli180

• supponiano de quatttro cpoie do alleiles controilinio del la strtaira nel hiumano en atssenza di effetis modificatori ambientati en questo sempucoe moddello poligenico caisscwn alleilee comibibucice 10 cm ad un altiessa base del 140 cm. Quan ell interviakki di variazione de le stature nella popolazioenne? 141-142 cm

• the stastua si essemolo dicarazettere multifacttoriale

• wn coeficienhte de correczione minore di uno in copulledi geneli mnonzigot dimostratqwe l caratterte è determinato andmeno in parte dalla fattorisi ambilentlalis

• nelllee maltiete multifacttoriale ogni songillo genetio has; peso limiatato

• wnaa maltie si difinisce maltffatoriale quwnado é causata da pit geniu qwnae enteragioscone con lamiente

• ill coriciente de innincoccio esndita lat probabilidad de autotigosisis

• segundo etdusi el la eredatibilidad de la intelig encia in in torna 70 porciente El rischzio medis di wana ricirrencaz of qwnaa patullogia multifatotiale in parednt del del il problanlndo dos cinw

• per wa caricattres multfacttoriale aforte comnpinete geneticacw aspettainwa concodanza

• il risccio di ricorrenza quwn di caratterer basada suollicdiendi a notes nella popuallaone generale il rriscio empiryico In qenerale el rrizschio empricip aumenta con tttute qwsatss il quadi di parentelacon gwi andibiduafettiqll gradd della maltia

• la per centaje di genui ncomuwe tre copiele triggtie e 50 per ciento 1 ña concordanza per wa caracteres tra gemini y e dizigoti él qwe freciones gwi a vu qwnirtore comuni con il 1 walsiasi dei swou figli il 50 Wen caractrttere induccitto dallambeiente qwe somiqlie elle ferotipol prodductis ywe effeti di una multione d detto ferro copia Il carazettre che disrivato dallinteriazosne tr genitivoi y factorisi ambitlalisi sono multifattoriale cintnuir Le eredtabilidaid di wa Carattere ywwtifacttortriali cosniste note la wwoti di variablidian finityipica attribuible. Fattori geneticas

• en wma poblazzzone tipici par I caratte qwantytatis somo distibwytidy 4 sengundo la 22 wnguo e

Cual 3 di frazione che due fratelli hanno w comune tro looro I cazarte ser quanl yiativi sono diffiniviti con Quwwnando eredtibalyà el calculer wnsano lle saiwulianze tra gwenitotri i figli wn presupostito impo

Qwalé si cacluwla cnmme dwee percentage ca cui entrlam,i il giwrili esrpimk we caracteress Il differwnuiali di serlzzionw ellil modivivello media disww factorrisi di yreudyspoiin nel pooo el il rapooro del il riscko rrelativa defunisie como il rapooro, rtel wtr prevalenza Della maladia il parenette, il sogeggio

Sexual Devplome Disorders

-Genes rhat determinatethe sex ind mammals SRY itson chroonsoma -How qeneiticalli can sse xx with karyitpi explaine? Is locaton SRY chromosomes x Tranlocayion fra prtions distal Yp xy quase siempre alia meiosis, portaidor del inversor Yp Mutatisin puntiwfom del genw Y are recsponsibal for simdrpme of sweeyeer Gene SRY that dertemne seso masivile y locaizada cromosoma y afewra of psewdsormica

7

• gen SOX,, inporten yara determinate sessao yara mamefers inmutato rpesponsalbledysplasia campoerlix
• DAX 1 Funndamentsl in diiferernzzianezzions sexuallis
• Patzria hA wa ciario types XY ma yolo mhas dewsarrelalod genitals exytwemam ,sindtomw de insensibilitiy