{"id":47904,"date":"2022-09-06T15:38:35","date_gmt":"2022-09-06T12:38:35","guid":{"rendered":"https:\/\/www.synevo.md\/?post_type=product&p=47904"},"modified":"2025-12-02T10:22:43","modified_gmt":"2025-12-02T08:22:43","slug":"analiza-cromozomiala-in-sange-cariotip-constitutional","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/analiza-cromozomiala-in-sange-cariotip-constitutional\/","title":{"rendered":"\u0425\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u044b\u0439 \u0430\u043d\u0430\u043b\u0438\u0437 \u043a\u0440\u043e\u0432\u0438 (\u043a\u043e\u043d\u0441\u0442\u0438\u0442\u0443\u0446\u0438\u043e\u043d\u0430\u043b\u044c\u043d\u044b\u0439 \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f)"},"content":{"rendered":"

\u041e\u0431\u0449\u0430\u044f \u0438\u043d\u0444\u043e\u0440\u043c\u0430\u0446\u0438\u044f<\/strong><\/em><\/p>\n

Testarea citogenetic\u0103 constituie parte integrant\u0103 a medicinii clinice deoarece identificarea unei abera\u0163ii cromozomiale specifice poate explica o anomalie fenotipic\u0103 \u015fi poate fi direct asociat\u0103 cu diagnosticul unei boli.<\/div>\n
Din acest motiv este esen\u0163ial s\u0103 se determine dac\u0103 o persoan\u0103 afectat\u0103 prezint\u0103\u00a0 un complement cromozomial ce difer\u0103 de pattern-ul standard al celor 23 perechi de cromozomi cu morfologie cunoscut\u0103.<\/div>\n
Exist\u0103 dou\u0103 categorii mari de anomalii citogenetice detectabile: de tip numeric \u015fi de tip structural.<\/div>\n

Anomalii cromozomiale numerice<\/em><\/strong><\/p>\n

Cariotipul<\/em>\u00a0unei specii, termen introdus de Levitsky in 1924, reprezint\u0103 num\u0103rul de cromozomi prezen\u0163i \u00een nucleul celulelor somatice. Cariotipul uman este alc\u0103tuit din\u00a046 cromozomi, organiza\u0163i \u00een 23\u00a0perechi; prin analiza citogenetic\u0103, cromozomii pot fi identifica\u0163i ca entit\u0103\u0163i structurale discrete, fiecare celul\u0103 uman\u0103 con\u0163in\u00e2nd 22 perechi de autozomi, precum \u015fi o pereche de cromozomi sexuali. Intr-o pereche de cromozomi unul este de provenien\u0163\u0103 matern\u0103, iar celel\u0103lalt de origine patern\u01031<\/sup>.<\/p>\n

Un set de 23 constuie num\u0103rul\u00a0haploid\u00a0<\/em>(N) de cromozomi \u015fi corespunde num\u0103rului de cromozomi dintr-un gamet. In procesul de fertilizare dou\u0103 seturi haploide se al\u0103tur\u0103 pentru a forma zigotul cu 46 cromozomi \u2013 setul diploid (2N) de cromozomi. Erorile survenite \u00een diviziunea celular\u0103 pot genera seturi de cromozomi care au mai mult sau mai pu\u0163in de 46 cromozomi. Prezen\u0163a \u00eentr-o celul\u0103 somatic\u0103 a unui multiplu exact al unui set haploid de cromozomi este denumit\u0103\u00a0euploidie<\/em>, \u00een timp ce pierderea sau prezen\u0163a \u00een plus a unuia sau mai multor cromozomi este cunoscut\u0103 ca\u00a0aneuploidie<\/em>.<\/p>\n

Diploidia<\/em>\u00a0\u2013 starea normal\u0103 a celulelor umane \u2013 reprezint\u0103 o forma de euploidie (eu \u2013\u00a0\u201cgood\u201d, ploid \u2013 \u201cset\u201d)\u00a0. Poliploidiile anormale includ\u00a0triploidia<\/em>\u00a0(3N = 69 cromozomi) \u015fi\u00a0tetraploidia<\/em>\u00a0(4N = 92 cromozomi), abera\u0163ii ce nu sunt compatibile cu via\u0163a \u015fi care sunt depistate \u00een principal \u00een produ\u015fii de concep\u0163ie avorta\u0163i spontan. Triploidia se poate datora unui e\u015fec \u00een gametogeneza ap\u0103rut la una din diviziunile meiotice, ce d\u0103 na\u015ftere unui gamet 2N, care atunci c\u00e2nd este fertilizat de c\u0103tre un gamet haploid provenit de la cel\u0103lalt p\u0103rinte, va produce un zigot triploid. Pe de alt\u0103 parte un set 3N mai poate fi derivat din\u00a0dispermie<\/em>\u00a0\u2013 fertilizarea unui ou haploid de c\u0103tre 2 spermatozoizi \u2013 ce d\u0103 na\u015ftere de obicei la o\u00a0mola hidatiform\u0103 par\u0163ial\u0103<\/em>. Tetraploidia este \u00een majoritatea cazurilor un eveniment postmeiotic care se prezint\u0103 ca o duplicare a unui set diploid (XXXX sau XXYY), ca urmare a unui e\u015fec ap\u0103rut \u00eentr-un clivaj mitotic precoce al zigotului1;3<\/sup>.<\/p>\n

Aneuploidia<\/em>\u00a0are ca mecanism de producere\u00a0nondisjunc\u0163ia\u00a0(lipsa de separare a comozomilor), care poate surveni fie \u00een meioz\u0103, fie \u00een mitoz\u0103. De obicei este afectat\u0103 o singur\u0103 pereche de cromozomi. Nondisjunc\u0163ia mitotic\u0103 precoce \u00eentr-un zigot poate da na\u015ftere la o abera\u0163ie cromozomial\u0103 prezent\u0103 \u00een toate celulele din organism, \u00een timp ce erorile de diviziune survenite mai tarziu conduc la\u00a0mozaicism<\/em>\u00a0\u2013 prezen\u0163a \u00een acela\u015fi organism a dou\u0103 linii celulare ce difer\u0103 \u00eentre ele printr-un cromozom.<\/p>\n

In meioza normal\u0103 o replicare ADN este urmat\u0103 de dou\u0103 diviziuni celulare ce au ca rezultat final\u00a0formarea de\u00a0game\u0163i haploizi. Prima diviziune meiotica se caracterizeaz\u0103 prin reducerea la jum\u0103tate a num\u0103rului total de cromozomi pe celula. A doua diviziune meiotic\u0103 este o simpl\u0103 diviziune de tip mitotic \u00een care are loc separarea centromerilor \u015fi distribu\u0163ia cromozomilor \u00een celulele-fiica. Erorile survenite \u00een meioz\u0103 pot da na\u015ftere la game\u0163i cu un cromozom \u00een deficit sau \u00een exces. Nondisjunc\u0163ia din cursul primei meioze va genera 2 game\u0163i care sunt\u00a0disomici<\/em>\u00a0pentru un cromozom \u015fi la 2 game\u0163i c\u0103rora le lipse\u015fte cromozomul respectiv (nulisomici<\/em>). Atunci c\u00e2nd are loc fertilizarea, primii game\u0163i vor da na\u015ftere la un produs de concep\u0163ie cu trisomie, \u00een timp ce \u00een al doilea caz va rezulta un zigot cu monosomie. Atunci c\u00e2nd eroarea survine \u00een cea de a doua diviziune meiotic\u0103 rezult\u0103 doi game\u0163i haploizi normal, un gamet disomic \u015fi unul nulisomic (vezi fig.19.1.1<\/em>).<\/p>\n

\"Analiza<\/a><\/p>\n

\"Analiza<\/a><\/p>\n

Fig. 19.1.1 Meioza<\/p>\n

A. Meioza normal\u0103; B. Nondisjunc\u0163ie \u00een prima diviziune meiotic\u0103; C. Nondisjunc\u0163ie \u00een a doua diviziune meiotic\u0103<\/p>\n

(Adaptare dup\u0103 medical-dictionary.thefreedictionary.com)<\/p>\n

Trisomia \u015f<\/em>i\u00a0monosomia<\/em>\u00a0pot afecta orice cromozom, \u00eens\u0103 majoritatea acestor abera\u0163ii sunt incompatibile cu via\u0163a \u015fi vor da na\u015ftere la un avort spontan. De exemplu, trisomia 16 este anomalia cea mai frecvent raportat\u0103 la analiza citogenetic\u0103 a produ\u015filor de concep\u0163ie avorta\u0163i ins\u0103 ea nu a fost descris\u0103 la nou-n\u0103scu\u0163ii vii. Trisomiile autozomale care se pot \u00eenso\u0163i de un f\u0103t viabil sunt cele care includ cromozomii 13, 18 \u015fi 21. Mai rar sunt identificate persoane cu mozaicism cromozomial care con\u0163in trisomiile 8, 9 sau 22. Trisomiile cromozomilor sexuali sunt viabile; singura monosomie viabil\u0103 este cea a cromozomului X (45, X)1;2<\/sup>.<\/p>\n

Deoarece trisomiile \u015fi monosomiile sunt \u00een general incompatibile cu via\u0163a s-a presupus c\u0103 acestea vor conduce inevitabil la avort spontan. Cu toate acestea, analizele moleculare au ar\u0103tat c\u0103 un mic procent al produ\u015filor de concep\u0163ie aneuploizi poate fi \u201csalvat\u201d \u015fi da na\u015ftere la un f\u0103t viabil. In cazul monosomiei \u201csalvarea\u201c este realizat\u0103 prin duplicarea singurului cromozom existent, rezult\u00e2nd o pereche de cromozomi cu\u00a0izodisomie uniparental\u0103<\/em>\u00a0(dou\u0103 copii ale aceluia\u015fi cromozom mo\u015ftenit de la un p\u0103rinte). Acest mecanism este exemplificat de o serie de comunic\u0103ri din literatur\u0103 \u00een care un copil afectat de fibroz\u0103 chistic\u0103 era homozigot pentru muta\u0163ia \u0394F508, de\u015fi analiza molecular\u0103 a ambilor p\u0103rin\u0163i a ar\u0103tat c\u0103 doar unul dintre ace\u015ftia era purt\u0103tor al muta\u0163iei. Explica\u0163ia a fost c\u0103 produsul de concep\u0163ie a prezentat o monosomie 7 ce fost \u201csalvat\u0103\u201d prin duplicarea cromozomului existent care, \u00eent\u00e2mpl\u0103tor, era purt\u0103tor al muta\u0163iei pentru fibroza chistic\u0103. O situa\u0163ie similar\u0103 este posibil\u0103 \u00een cazul trisomiei. Cele mai multe trisomii nu sunt viabile, dar dac\u0103 unul din cei trei cromozomi este eliminat, rezult\u0103 o disomie pentru acea pereche de cromozomi, cu urm\u0103toarele posibilit\u0103\u0163i:<\/p>\n

\u2013 pierderea unui cromozom va da na\u015ftere, \u00een dou\u0103 treimi din cazuri, la o pereche de cromozomi, \u00een care unul are provenien\u0163\u0103 matern\u0103 \u015fi cel\u0103lalt patern\u0103 (heterodisomie biparental\u0103<\/em>);<\/div>\n
<\/div>\n
\u2013 \u00een o treime din cazuri va rezulta o pereche de cromozomi care provin de la acela\u015fi p\u0103rinte\u00a0(heterodisomie uniparentala).<\/em><\/div>\n

In aceast\u0103 situa\u0163ie este important momentul \u00een care survine eroarea de diviziune. Astfel, o nondisjunc\u0163ie ap\u0103rut\u0103 \u00een prima diviziune meiotic\u0103 va genera o\u00a0heterodisomie<\/em>\u00a0uniparental\u0103<\/em>\u00a0(2 cromozomi omologi heterozigo\u0163i proveni\u0163i de la acela\u015fi p\u0103rinte), \u00een timp ce o nondisjunc\u0163ie \u00een cea de a doua diviziune va rezulta \u00eentr-o\u00a0izodisomie uniparental\u0103\u00a0<\/em>(dou\u0103 copii ale unui singur cromozom) \u2013\u00a0vezi figura 19.1.2.;\u00a0<\/em>dar crossing-over poate complica situa\u0163ia.<\/p>\n

\"Analiza<\/a>\"Analiza<\/a><\/p>\n

Fig. 19.1.2\u00a0 Tipuri de disomie uniparental\u0103 produse de erori de diviziune<\/p>\n

(Adaptare dup\u0103 Uniparental Disomy; Gene Reviews\u00a0www.be-md.ncbi.nlm.nih.gov<\/a>)<\/p>\n

De\u015fi se credea c\u0103 a avea o pereche de cromozomi este suficient, datele actuale arat\u0103 c\u0103, \u00een unele cazuri, este necesar ca perechile s\u0103 con\u0163in\u0103 un cromozom de provenien\u0163\u0103 matern\u0103 \u015fi unul patern\u0103. Problemele de disomie uniparental\u0103 vs biparental\u0103 ca \u015fi de isodisomie vs heterodisomie au o importan\u0163\u0103 major\u0103 pentru\u00a0fenomenul de amprentare<\/em>\u00a0(exprimarea diferen\u0163iat\u0103 a genelor \u00een func\u0163ie de originea lor parental\u0103)1<\/sup>.<\/p>\n

Aneuploidii autozomale<\/p>\n

Cea mai obi\u015fnuit\u0103 cauz\u0103 de retard mental, av\u00e2nd o inciden\u0163\u0103 de 1 la 700 na\u015fteri, este\u00a0trisomia 21<\/em>\u00a0\u0438\u043b\u0438\u00a0sindromul Down<\/em>. Nou-n\u0103scutul cu trisomie 21 are lungime \u015fi greutate mai mic\u0103 dec\u00e2t parametri v\u00e2rstei gesta\u0163ionale, prezint\u0103 hipotonie muscular\u0103, hiperextensibilitate \u015fi reflexe comportamentale (de exemplu refexul Moro) reduse. Capul este brahicefalic, cu occiput turtit \u015fi fontanele largi. Fa\u0163a este rotund\u0103, plat\u0103 \u015fi prezint\u0103 o dismorfie sugestiv\u0103: epicantus (un repliu in unghiul intern al ochiului), fantele palpebrale oblice \u00een sus \u015fi \u00een afar\u0103; nasul mic cu r\u0103d\u0103cina turtit\u0103 \u015fi n\u0103rile mici \u015fi anteversate; gura deschis\u0103 \u015fi protruzie lingual\u0103 (datorit\u0103 cavit\u0103\u0163ii orale mici); urechile mai jos situate, mici \u015fi displazice. G\u00e2tul este scurt, cu exces de piele pe ceaf\u0103; m\u00e2inile sunt scurte \u015fi late, cu brahidactilie, clinodactilie (incurbare) a degetului V \u015fi, frecvent, un singur pliu de flexie palmar\u0103 (pliu simian);\u00a0 inconstant sunt prezente unele malforma\u0163ii viscerale (defecte cardiace, atrezie duodenal\u0103, imperfora\u0163ie anal\u0103).<\/p>\n

Aproximativ 92.5% din persoanele cu sindrom Down prezint\u0103 47 cromozomi (sunt incluse 3 copii ale cromozomului 21) ca urmare a unei nondisjunc\u0163ii ap\u0103rute in meioza. Sub 3% dintre pacien\u0163i exprim\u0103 un fenotip mai pu\u0163in sever datorit\u0103 unui mozaicism caracterizat prin 2 linii celulare (47,XX,+21\/46, XX sau 47,XY,+21\/46,XY) \u015fi aproximativ 5% au doar 46 cromozomi, deoarece cromozomul 21 in exces face parte dintr-o transloca\u0163ie robertsonian\u0103 sau un alt tip de transloca\u0163ie. Faptul c\u0103 un copil prezint\u0103 o transloca\u0163ie reprezint\u0103 un indiciu c\u0103 unul dintre p\u0103rin\u0163i ar putea fi purt\u0103tor al unei astfel de anomalii structurale \u015fi de aceea este important s\u0103 se stabileasc\u0103 cariotipul fiec\u0103rui p\u0103rinte pentru a vedea dac\u0103 respectivul cuplu prezint\u0103 riscul de a mai avea un copil cu sindrom Down la sarcinile ulterioare. De\u015fi in majoritatea cazurilor un pacient cu sindrom Down de\u0163ine 3 copii complete ale cromozomului 21, studiile moleculare ale persoanelor cu rearanj\u0103ri ale cromozomului 21 au ar\u0103tat \u00een mod clar c\u0103 sunt necesare doar 3 copii ale regiunii cromozomului 21 ce con\u0163ine benzile 21q22.12-21q22.3, denumit\u0103 regiunea critic\u0103 pentru sindromul Down.<\/p>\n

Celelalte dou\u0103 trisomii viabile sunt trisomia 13 \u015fi trisomia 18. Trisomia 13<\/em>\u00a0\u0438\u043b\u0438\u00a0sindromul Patau<\/em>\u00a0este \u00eent\u00e2lnit\u0103 cu o inciden\u0163\u0103 de 1:4000-1:10 000 na\u015fteri. Se caracterizeaz\u0103 prin microcefalie, defecte ale scalpului, fisur\u0103 labio-palatin\u0103, ciclopie, cataract\u0103, displazie retinian\u0103, polidactilie, pliu simian, c\u0103lc\u00e2i proeminent, defect septal ventricular, polichistoza renal\u0103, uter bifid, criptorhidrie, hipospadias, retard mintal sever.\u00a0Trisomia 18<\/em>\u00a0\u0438\u043b\u0438\u00a0sindromul Edwards<\/em>, are o inciden\u0163\u0103 de 1:8000 nou-n\u0103scu\u0163i; tr\u0103s\u0103turile clinice includ greutate mic\u0103 la na\u015ftere, microcefalie, occiput proeminent, micrognatie, urechi jos inserate cu pavilionul modificat, fisur\u0103 de palat sau palat ogival, anomalii ale dermatoglifelor, haluce in dosiflexie, defect septal ventricular, rinichi in potcoav\u0103, retard mintal sever.<\/p>\n

Dac\u0103 pacien\u0163ii cu sindrom Down pot supravie\u0163ui p\u00e2n\u0103 \u00een cea de-a doua sau a treia decad\u0103 de via\u0163a, cei cu trisomie 13 sau 18 decedeaz\u0103 de obicei \u00een prima lun\u0103. Din aceste motive, consilierea genetic\u0103 include op\u0163iunea de \u00eentrerupere a sarcinii.<\/p>\n

Aneuploidiile cromozomilor sexuali<\/p>\n

Sunt relativ frecvente \u00een popula\u0163ie (prevalen\u0163a globala de 1:500 na\u015fteri) \u015fi exprim\u0103 un fenotip mai pu\u0163in sever \u00een compara\u0163ie cu aneuploidiile autozomale datorit\u0103 efectului de inactivare a cromozomului X precum \u015fi a num\u0103rului limitat de gene situate pe cromozomul Y.<\/p>\n

In majoritatea cazurilor, aneuploidiile cromozomilor sexuali sunt reprezentate de patru afec\u0163iuni mai frecvente: trei trisomii \u015fi o monosomie.<\/p>\n

Cariotipurile aberante ale persoanelor care prezint\u0103 3 cromozomi X\u00a0(femei 47,XXX<\/em>) sau 1 cromozom X \u015fi doi cromozomi Y (b\u0103rba\u0163i 47,XYY<\/em>) trec adesea neobservate \u00een cursul vie\u0163ii. Inciden\u0163a acestora la na\u015ftere este de 1:1000, ins\u0103, cu excep\u0163ia unei staturi mai inalte, nu exist\u0103 alte tras\u0103turi care s\u0103 sugereze o anomalie cromozomial\u0103. Unele persoane prezint\u0103 tulbur\u0103ri de \u00eenv\u0103\u0163are \u015fi pot fi astfel identificate prin programele \u015fcolare de screening. Femeile XXX \u015fi b\u0103rba\u0163ii XXY sunt depista\u0163i, de asemenea, \u00een clinicile de infertilitate, de\u015fi anomalia citogenetic\u0103 nu induce tulbur\u0103ri ale fertilit\u0103\u0163ii. Indivizii XYY au inciden\u0163a crescut\u0103 de tulbur\u0103ri comportamentale, iar date mai vechi, care ulterior au fost infirmate, au asociat anomalia de cariotip cu o rat\u0103 mai mare a criminalit\u0103\u0163ii.<\/p>\n

B\u0103rba\u0163ii cu\u00a0sindromul Klinefelter<\/em>\u00a0(47,XXY) au tendin\u0163a de a fi mai inal\u0163i \u015fi mai slabi \u00een compara\u0163ie cu persoanele de aceea\u015fi v\u00e2rst\u0103 din jurul lor. Principalele tr\u0103s\u0103turi clinice sunt: hipogonadismul postpubertal, dezvoltarea s\u00e2nilor, infertilitate datorat\u0103 testiculelor mici cu tubi hialinizati \u015fi azoospermie. Exist\u0103 o form\u0103 mai atenuat\u0103 de sindrom Klinefelter asociat\u0103 cu un oarecare poten\u0163ial fertil ca urmare a unui mozaic cromozomial: 47,XXY\/46XY; propor\u0163ia relativ\u0103 de celule XY vs celule XXY la zigot \u00een cursul determin\u0103rii sexului este esen\u0163ial\u0103 pentru fertilitate.<\/p>\n

Cea mai frecvent identificat\u0103 aneuploidie a cromozomilor sexuali asociat\u0103 cu fenotip feminin este\u00a0sindromul Turner<\/em>\u00a0-\u00a045,X<\/em>. Aproximativ jum\u0103tate din persoanele cu acest sindrom prezint\u0103 monosomia clasic\u0103 45,X. Singurul cromozom X este de obicei de origine matern\u0103 suger\u00e2nd faptul c\u0103 nondisjunc\u0163ia meiotic\u0103 patern\u0103 constituie cea mai frecvent\u0103 surs\u0103 de eroare. In plus, fa\u0163\u0103 de 45,X pot exista \u015fi cariotipuri mai complexe (de exemplu, dele\u0163ii de cromozom X, prezen\u0163a unui cromozom X inelar sau izocromozom X, mozaicuri cromozomiale: 45,X\/46,XX; 45,X\/46,XY). Cea mai sever\u0103 este situa\u0163ia \u00een care exist\u0103 cel pu\u0163in o linie celular\u0103 cu un cromozom Y par\u0163ial sau complet, datorit\u0103 riscului crescut de gonadoblastom.<\/p>\n

Fenotipul asociat sindromului Turner este foarte variabil. Persoanele afectate au de obicei o statur\u0103 mic\u0103 (<150 cm) cu disgenezie gonadal\u0103 \u015fi tulbur\u0103ri de \u00eenv\u0103\u0163are. Alte tr\u0103s\u0103turi comune includ: o plic\u0103 de piele ce se intinde de la creasta omoplatului pan\u0103 la zona nucal\u0103 (g\u00e2t palmat), torace in form\u0103 de scut, inser\u0163ie posterioar\u0103 joas\u0103 a p\u0103rului, cubitus valgus, malforma\u0163ii cardiace sau renale.<\/p>\n

Hygroma chistic\u0103<\/em>\u00a0este aspectul ecografic prenatal caracteristic, corespunz\u0103tor unei mase chistice septate \u00een regiunea nucal\u0103 fetal\u0103; aceasta apare, cel mai probabil, din cauza dezvolt\u0103rii anormale a limfaticelor mari fetale. Alte semne ecografice majore \u00een sindromul Turner sunt: defecte ale inimii st\u00e2ngi, malforma\u021bii renale \u0219i scheletale, anasarca sau hidrops fetal. Translucen\u021ba nucal\u0103 este, de obicei, crescut\u0103 in trimestrul I de sarcin\u0103.<\/p>\n

Persoanele cu sindrom Turner prezint\u0103, de obicei, un nivel normal de inteligen\u0163\u0103, de\u015fi acesta poate fi variabil, exist\u00e2nd chiar cazuri de handicapuri mentale semnificative. De\u015fi infertilitatea este o tr\u0103s\u0103tura definitorie a acestui sindrom, dezvoltarea tehnicilor de reproducere asistat\u0103 a\u00a0permis ca unele femei afectate (in special cele cu cariotipuri mozaicate) s\u0103 ob\u0163in\u0103 \u015fi s\u0103 duc\u0103 la termen o sarcin\u0103 normal\u01031;3<\/sup>.<\/p>\n

Anomalii cromozomiale structurale<\/em><\/strong><\/p>\n

Cromozomii nu sunt structuri statice, astfel c\u0103 at\u00e2t \u00een cursul meiozei c\u00e2t \u015fi al mitozei au loc fenomene de recombinare. Recombinarea este un proces natural care asigur\u0103 variabilitatea speciilor. Cu toate c\u0103 exist\u0103 un sistem de reglare foarte dezvoltat pentru a preveni erorile de recombinare, acestea se produc totu\u015fi, conduc\u00e2nd uneori la rearanj\u0103ri care schimb\u0103 structura unuia sau mai multor cromozomi. Rearanj\u0103rile pot fi:<\/p>\n

-\u00a0echilibrate<\/em>, dac\u0103 materialul cromozomial este prezent \u015fi func\u0163ional \u00een totalitate \u00eens\u0103 aranjat \u00eentr-o conforma\u0163ie diferit\u0103;<\/div>\n
<\/div>\n
-\u00a0neechilibrate,<\/em>\u00a0dac\u0103 exist\u0103 pierderi \u015fi\/sau duplic\u0103ri ale unui material cromozomial.<\/div>\n

Rearanj\u0103rile echilibrate sunt\u00a0de obicei benigne, din punct de vedere clinic, \u015fi tind s\u0103 se transmit\u0103 stabil; pot cre\u015fte \u00eens\u0103 riscul de erori survenite \u00een meioz\u0103 ce pot genera anomalii cromozomiale la f\u0103t \u015fi nou-n\u0103scut. Rearanj\u0103rile neechilibrate sunt \u00een general asociate cu un fenotip anormal ce include adesea \u00eent\u00e2rziere \u00een dezvoltare \u015fi retard mintal.<\/p>\n

Anomaliile cromozomiale structurale sunt reprezentate de:<\/p>\n

1. Dele\u0163ie\u00a0\u2013 pierderea unei por\u0163iuni dintr-un cromozom ce conduce la monosomie par\u0163ial\u0103; dele\u0163iile variaz\u0103 \u00een dimensiuni (de la foarte mici la\u00a0largi) \u015fi pot fi\u00a0terminale<\/em>\u00a0(pierderea cromozomial\u0103 include \u015fi telomerul) sau\u00a0intersti\u0163iale<\/em>\u00a0(pierderea unei por\u0163iuni interne a cromozomului); dele\u0163iile pot ap\u0103rea ca urmare a unei rupturi cromozomiale, a unui crossing-over inegal sau a nondisjunc\u0163iilor (vezi figura 19.1.3<\/em>).<\/p>\n

\"Analiza<\/a><\/p>\n

Fig. 19.1.3 Dele\u0163ie<\/p>\n

(Adaptare dup\u0103 Genetic Homes Reference \u2013 Chromosomal Deletion)<\/p>\n

2. Duplica\u0163ie\u00a0\u00a0\u2013 prezen\u0163a unei copii suplimentare a unui segment cromozomial ce conduce la o trisomie par\u0163ial\u0103; acest\u0103 anomalie poate fi de asemenea\u00a0terminal\u0103<\/em>\u00a0\u0438\u043b\u0438\u00a0intersti\u0163ial\u0103<\/em>; se produc printr-un mecanism similar dele\u0163iilor \u015fi cu c\u00e2t segmentul duplicat este mai mare cu at\u00e2t anomaliile clinice vor fi mai severe (vezi figura 19.1.4<\/em>).<\/p>\n

\"Analiza<\/a><\/p>\n

\"Analiza<\/a><\/p>\n

Fig. 19.1.4 Duplica\u0163ie<\/p>\n

(Adaptare dup\u0103 Genetic Homes Reference \u2013 Chromosomal Duplication)<\/p>\n

3. Inversie\u00a0\u2013 amplasarea unor segmente cromozomiale \u00een pozi\u0163ii inversate fa\u0163\u0103 de configura\u0163ia normal\u0103 a genelor; necesit\u0103 cel pu\u0163in dou\u0103 puncte de ruptur\u0103 la nivelul cromozomului; inversiile pot fi\u00a0paracentrice<\/em>\u00a0(cele dou\u0103 puncte de ruptur\u0103 se g\u0103sesc de aceea\u015fi parte a centromerului, pe acela\u015fi bra\u0163) sau\u00a0pericentrice<\/em>\u00a0(punctele de ruptur\u0103 se g\u0103sesc de o parte \u015fi de alta a centromerului \u015fi implic\u0103 ambele bra\u0163e ale cromozomului); majoritatea inversiilor sunt echilibrate, dar dac\u0103 ruptura se produce \u00een interiorul unei gene este perturbat\u0103 sinteza produsului genei respective\u00a0\u015fi pot fi generate anomalii clinice; exist\u0103 un risc crescut de erori survenite \u00een cursul meiozei, iar purt\u0103torii de inversii prezint\u0103 adesea infertilitate sau pierderi precoce de sarcin\u0103 ca urmare a unor produ\u015fi de concep\u0163ie cu dezechilibru cromozomial; astfel, \u00een cazul inversiilor paracentrice pot ap\u0103rea, ca urmare a recombinarii meiotice, cromozomi acentrici sau dicentrici non-viabili (teoretic, nu practic), iar \u00een cazul inversiilor pericentrice este posibil s\u0103 fie genera\u0163i game\u0163i cu duplica\u0163ii \u015fi\/sau dele\u0163ii (vezi figurile 19.1.5 \u015fi 19.1.6<\/em>).<\/p>\n

\u00a0<\/strong>\"Analiza<\/a><\/p>\n

\"Analiza<\/a><\/p>\n

Fig.19.1.5\u00a0\u00a0\u00a0 Inversie paracentric\u0103<\/p>\n

\"Analiza<\/a><\/p>\n

Fig.19.1.6\u00a0\u00a0 Inversie pericentric\u0103<\/p>\n

4. Transloca\u0163ie clasic\u0103 (reciproc\u0103)\u00a0\u2013 rearanjare care implic\u0103 unul sau mai mul\u0163i cromozomi neomologi; fiecare cromozom prezint\u0103 un singur punct de ruptur\u0103, iar segmentele rezultate i\u015fi schimb\u0103 locul \u00eentre ele generand doi sau mai mul\u0163i cromozomi deriva\u0163i; la fel ca \u015fi inversiile, majoritatea transloca\u0163iilor sunt echilibrate \u015fi\u00a0 principala problem\u0103 o reprezint\u0103 riscul crescut de anomalii cromozomiale la produ\u015fii de concep\u0163ie ai purt\u0103torilor de transloca\u0163ii; astfel, \u00een cursul meiozei pot rezulta game\u0163i cu dele\u0163ii\/duplica\u0163ii, dac\u0103 \u00een anafaz\u0103 cromozomii deriva\u0163i nu segreg\u0103 \u00eempreun\u0103 (p\u00e2n\u0103 la o treime din cazuri); cromozomii pot urma \u015fi un model de segregare 3:1 \u00een care 3 cromozomi sunt separa\u0163i unul \u00eentr-o celul\u0103 \u015fi unul \u00een cea de-a doua celul\u0103 (vezi figura 19.1.7<\/em>).<\/p>\n

\"Analiza<\/a>\"Analiza<\/a><\/p>\n

Fig.19.1.7\u00a0 Transloca\u0163ie clasic\u0103<\/p>\n

(Adaptare dup\u0103 Genetics Primer \u2013 http:\/\/members.cox.net)<\/p>\n

5. Transloca\u0163ie robertsonian\u0103\u00a0\u2013 constituie o variant\u0103 a transloca\u0163iei clasice; se produce \u00eentre doi cromozomi acrocentrici prin pierderea, de obicei, a unui segment din bra\u0163ele scurte, cu p\u0103strarea bra\u0163elor lungi; de obicei nu sunt consecin\u0163e clinice deoarece pe to\u0163i cromozomii acrocentrici sunt localizate copii multiple ale genelor ARNr; purt\u0103torii acestui tip de transloca\u0163ie au un num\u0103r de 45 cromozomi, deoarece doi cromozomi au devenit unul singur din punct de vedere func\u0163ional \u015fi prezint\u0103 acela\u015fi centromer activ; exist\u0103 un risc crescut de nondisjunc\u0163ii meiotice rezult\u00e2nd produ\u015fi de concep\u0163ie cu trisomie fa\u0163\u0103 de unul din cromozomii rearanja\u0163i; cel mai obi\u015fnuit exemplu este transloca\u0163ia ce implic\u0103 cromozomii 13 \u015fi 14 ai c\u0103rei purt\u0103tori pot da na\u015ftere unor copii cu trisomie 13 (cariotip cu 46 cromozomi, 2 copii de cromozom 13 \u015fi transloca\u0163ie robertsonian\u0103 13;14); de obicei transloca\u0163ia implic\u0103 doi cromozomi neomologi, \u00eens\u0103 pot exista situa\u0163ii \u00een care sunt afecta\u0163i cromozomi omologi: de exemplu, transloca\u0163ia robertsonian\u0103\u00a0de novo<\/em>\u00a021;21 ai c\u0103rei purt\u0103tori pot da na\u015ftere unor copii cu sindrom Down (vezi figura 19.1.8<\/em>).<\/p>\n

\"Analiza\u00a0<\/a>\"Analiza<\/a><\/p>\n

Fig. 19.1.8 Transloca\u0163ie robertsonian\u0103<\/p>\n

(Adaptare dup\u0103 Cytogenetics \u2013 www.ucl.ac.uk)<\/p>\n

6. Izocromozom\u00a0\u2013 reprezint\u0103 un cromozom ce apare ca urmare a unei erori de diviziune a centromerului: sunt generate dou\u0103 copii ale unui bra\u0163 cromozomial cu lipsa celuilalt bra\u0163; rezult\u0103 astfel doi cromozomi deriva\u0163i, unul cu o duplica\u0163ie inversat\u0103 a bra\u0163ului lung, cel\u0103lalt cu o duplica\u0163ie inversat\u0103 a bra\u0163ului scurt; dac\u0103 ambii izocromozomi sunt men\u0163inu\u0163i \u00eentr-o celul\u0103 va rezulta o trisomie pentru cromozomul de baz\u0103, condi\u0163ie ce este de obicei incompatibil\u0103 cu via\u0163a; dac\u0103 \u00eens\u0103 este men\u0163inut doar un singur izocromozom \u00een celul\u0103 va rezulta o trisomie pentru unul din bra\u0163ele cromozomiale duplicate \u015fi o monosomie pentru cel\u0103lalt bra\u0163; cel mai cunoscut exemplu este izocromozomul bra\u0163ului lung al cromozomului X care poate s\u0103 apar\u0103 la unele paciente cu sindrom Turner (monosomia pentru bra\u0163ul scurt al izocromozomului X induce o dezvoltare anormal\u0103) (vezi figura 19.1.9).<\/em><\/p>\n

\"Analiza<\/a>\"Analiza<\/a><\/strong><\/p>\n

Fig. 19.1.9 Izocromozomi<\/p>\n

(Adaptare dup\u0103 Genetic Homes Reference \u2013 Isochromosomes)<\/p>\n

7. Cromozom inelar\u00a0\u2013 reprezint\u0103 un cromozom ce rezult\u0103 prin pierderea ambelor telomere \u015fi fuziunea circular\u0103 a por\u0163iunii restante \u00een vederea refacerii stabilit\u0103\u0163ii cromozomiale; \u00een majoritatea cazurilor acest tip de structur\u0103 este instabil, \u00eens\u0103 exist\u0103 unele situa\u0163ii \u00een care cromozomii inelari pot fi transmi\u015fi la celulele-fiice (vezi figura 19.1.10<\/em>).<\/p>\n

\"Analiza<\/a>\"Analiza<\/a><\/p>\n

Fig. 19.1.10 Cromozom inelar<\/p>\n

(Adaptare dup\u0103 Genetic Homes Reference \u2013 Ring Chromosome)<\/p>\n

8. Cromozom marker\u00a0\u2013 constituie un cromozom cu un centromer ce este transmis stabil la celulele-fiice, dar care nu poate fi clar identificat, fie datorit\u0103 dimensiunii sale prea mici, fie datorit\u0103 aspectului la bandare prea ambiguu. Tehnica SKY (Spectral Karyotyping) constituie un instrument util pentru determinarea originii marker-ilor1;2<\/sup>.<\/p>\n

A fost descris un num\u0103r semnificativ de sindroame asociate direct cu o anomalie cromozomial\u0103 structural\u0103.<\/p>\n

Sindroamele\u00a0de dele\u0163ii autozomale<\/em><\/p>\n

Dele\u0163iile sau duplica\u0163iile ce pot fi identificate citogenetic (clasic \u015fi molecular)\u00a0pot cauza tulbur\u0103ri de dezvoltare (retard de cre\u015ftere,\u00a0psihomotor) \u015fi malforma\u0163ii congenitale, fiind asociate de cele mai multe ori cu un fenotip caracteristic.<\/div>\n
Cele mai importante dele\u0163ii\u00a0 sunt reprezentate de: 4p-, 5p-, 11p-, 11q-, 13q-, 18p- \u015fi 18q-.<\/div>\n
O alt\u0103 categorie de dele\u0163ii subtelomerice sunt detectabile doar prin tehnica FISH sau prin alte metode moleculare.<\/div>\n
Majoritatea dele\u0163iilor \u015fi duplica\u0163iilor survin\u00a0de novo,\u00a0<\/em>dar exist\u0103 \u015fi mo\u015ftenite \u00een ~10% din cazurile de sindrom dele\u0163ie 22q11.2<\/div>\n

Dele\u0163ia 4p- (sindromul Wolf-Hirschhorn)<\/em><\/p>\n

Se caracterizeaz\u0103 clinic prin retard de cre\u015ftere, retard mintal sever, facies \u00een \u201ccoif de razboinic grec\u201d cu frunte \u015fi glabela proeminente, spr\u00e2ncene arcuite \u015fi nas lung, ochi \u00eendep\u0103rta\u0163i (hipertelorism) \u015fi \u00eendrepta\u0163i \u00een jos (fante antimongoliene), pliu cutanat suplimentar \u00een unghiul intern al ochiului (epicantus), strabism, colobom\u0103 \u015fi alte anomalii oculare, nas turtit, gura cu buza superioara scurt\u0103, despic\u0103tura labial\u0103 sau palatin\u0103 (\u201cbuz\u0103 de iepure\u201d sau \u201cgur\u0103 de lup\u201d), b\u0103rbie mic\u0103 (microretrogna\u0163ie), urechi jos implantate, mari, cu forma anormal\u0103; surditate, malforma\u0163ii cardiace, pulmonare sau renale, hipospadias.\u00a0Dele\u0163iile bra\u0163ului scurt al cromozomului 4 pot avea dimensiuni variabile; uneori sunt at\u00e2t de mici \u00eenc\u00e2t nu pot fi detectate dec\u00e2t prin tehnica FISH.<\/p>\n

Dele\u0163ia 5p- (sindromul Cri-Du-Chat)<\/em><\/p>\n

Descris \u00een 1963 de c\u0103tre Lejeune \u015fi colaboratorii s\u0103i, acest sindrom include un fenotip caractersitic: laringe anormal dezvoltat ce reprezint\u0103 cauza \u0163ip\u0103tului ascu\u0163it (ca cel al unei pisici), microcefalie, microgna\u0163ie, hipertelorism, fante antimongoliene, pliu palmar unic, hipotonie, retard mintal.\u00a0Dele\u0163iile pot avea dimensiuni variabile, \u00eens\u0103 regiunea critic\u0103 este 5p15.2.<\/p>\n

Sindroamele\u00a0de microdele\u0163ii<\/em><\/p>\n

Prin defini\u0163ie, microdele\u0163ia reprezint\u0103 o dele\u0163ie foarte mic\u0103, care afecteaz\u0103 doar o por\u0163iune dintr-o band\u0103 cromozomial\u0103. De\u015fi dimensiunile microdele\u0163iilor sunt mici, acestea sunt semnificativ mai mari (>500 kb) dec\u00e2t dele\u0163iile moleculare tipice, astfel \u00eenc\u00e2t unele pot fi detectate chiar prin efectuarea cariotipului clasic; majoritatea microdele\u0163iilor sunt \u00eens\u0103 identificate prin tehnica FISH.<\/p>\n

De\u015fi s-a crezut ini\u0163ial c\u0103 este vorba de dele\u0163ii \u00een cadrul unor gene singulare s-a descoperit c\u0103 multe sindroame se datoreaz\u0103 de fapt unor dele\u0163ii care cuprind por\u0163iuni din gene adiacente diferite. M\u0103rimea dele\u0163iei \u015fi num\u0103rul genelor implicate sunt variabile, astfel c\u0103 fenotipul exprimat poate s\u0103 difere semnificativ \u00eentre persoanele afectate. Aceste sindroame mai sunt denumite\u00a0sindroame de contiguitate genic\u0103<\/em>:<\/p>\n

Sindromul Miller-Dieker<\/em><\/p>\n

A fost asociat cu o microdele\u0163ie a por\u0163iunii distale a bra\u0163ului scurt al cromozomului 17 (17p13.3). Elementele clinice caracteristice sunt aspectul particular al fe\u0163ei \u015fi anomaliile cerebrale: lisencefalia (suprafa\u0163a neted\u0103 a emisferelor cerebrale), agenezia de corp calos \u015fi calcific\u0103rile de pe linia median\u0103 ce explic\u0103 retardul\u00a0 mintal sever \u015fi convulsiile. Lisencefalia izolat\u0103 a fost recunoscut\u0103 ca entitate separat\u0103 asociat\u0103 cu o muta\u0163ie a genei LIS1. Sindromul Miller-Dieker este mai complex fiind afectate cel putin dou\u0103 gene.<\/p>\n

Sindromul Prader-Willi<\/em>\u00a0si\u00a0sindromul Angelman<\/em>\u00a0sunt cele mai cunoscute sindroame de microdele\u0163ie. Ambele prezint\u0103 aceea\u015fi dele\u0163ie intersti\u0163ial\u0103 a por\u0163iunii proximale a bra\u0163ului lung al cromozomului 15 \u2013 del(15)(q11.2q13) \u2013 \u00eens\u0103 tabloul clinic este semnificativ diferit. Acest fapt este explicat prin fenomenul de amprentare: dac\u0103 dele\u0163ia afecteaz\u0103 cromozomul de origine patern\u0103 rezult\u0103\u00a0sindromul Prader-Willi<\/em>, iar dac\u0103 este implicat cromozomul de origine matern\u0103 se dezvolt\u0103\u00a0sindromul Angelman<\/em>.<\/p>\n

Pacien\u0163ii cu sindrom Prader-Willi prezint\u0103 hipotonie sever\u0103 \u015fi greutate mic\u0103 la na\u015ftere, \u00eens\u0103 \u00een cursul primului an de via\u0163\u0103 \u00eencep s\u0103 c\u00e2\u015ftige rapid \u00een greutate. Dac\u0103 nu se instituie o diet\u0103 corespunz\u0103toare se instaleaz\u0103 obezitate prin hiperfagie. Alte tr\u0103s\u0103turi clinice includ m\u00e2ini \u015fi picioare mici, hipogonadism, retard mintal moderat \u015fi un comportament particular cu reac\u0163ii violente. Pe de alt\u0103 parte, pacien\u0163ii cu sindrom Angelman prezint\u0103 un retard mintal sever, tulbur\u0103ri de vorbire, discursul fiind \u00eentrerupt adesea de accese de r\u00e2s inadecvate situa\u0163iei, hiperactivitate, statur\u0103 mic\u0103, microcefalie, convulsii \u015fi ataxie.<\/p>\n

Prin tehnica citogenetic\u0103 conven\u0163ional\u0103 poate fi detectat\u0103 dele\u0163ia 15q la aproximativ 60% din persoanele cu sindrom Prader-Willi \u015fi doar la 10-20% dintre cele cu sindrom Angelman. Prin tehnica FISH pot fi detectate dele\u0163ii \u00een 80-85% din cazuri, pentru ambele sindroame. Faptul c\u0103 nu pot fi detectate dele\u0163ii \u00een toate cazurile a ridicat suspiciunea existen\u0163ei unui alt tip de anomalie. La ora actual\u0103 se consider\u0103 ca\u00a0sindromul Prader-Willi<\/em>\u00a0\u0438\u00a0sindromul Angelman<\/em>\u00a0sunt asociate cu defecte de amprentare, iar procesele muta\u0163ionale cauzatoare de boal\u0103 sunt mult mai complexe dec\u00e2t o simpl\u0103 dele\u0163ie a ADN-ului.<\/p>\n

Sindromul Williams<\/em><\/p>\n

A fost asociat cu o dele\u0163ie\u00a0 ce cuprinde inclusiv\u00a0 gena elastinei (ELN) localizat\u0103 \u00een por\u0163iunea proximal\u0103 a bra\u0163ului lung a cromozomului 7 (7q11.23). Se caracterizeaz\u0103 clinic prin anomalii cardiace, hipertensiune arterial\u0103, voce r\u0103gusit\u0103, \u00eemb\u0103tr\u00e2nirea prematur\u0103 a pielii, tulbur\u0103ri comportamentale la care se adaug\u0103 hipercalcemie \u015fi\/sau hipercalciurie. Dac\u0103 absen\u0163a elastinei explic\u0103 multe dintre anomaliile fizice asociate cu acest sindrom, totu\u015fi aceasta nu poate fi asociat\u0103 cu tulbur\u0103rile comportamentale. In concep\u0163ia curent\u0103,\u00a0sindromul Williams<\/em>\u00a0este un sindrom de contiguitate genic\u0103, iar variabilitatea fenotipic\u0103 este dependent\u0103 de num\u0103rul genelor adiacente afectate de dele\u0163ie al\u0103turi de ELN.<\/p>\n

Diagnosticul se stabile\u015fte prin efectuarea cariotipului pentru identificarea rearanjamentelor cromozomiale care pot include regiunea 7q11.23, urmat de testul FISH, cu sonde ADN pentru regiunea critic\u0103 deletat\u0103 care include genele ELN \u015fi LIMK1.<\/p>\n

Sindromul WAGR<\/em><\/p>\n

Este un sindrom de contiguitate genic\u0103 bine definit, ce include tumora Wilms, aniridie, defecte genito-urinare \u015fi retard mintal. Cu excep\u0163ia defectelor genito-urinare care par s\u0103 fie cauzate de o variant\u0103 a muta\u0163iei de la nivelul locusului tumorii Wilms, fiecare din cele 3 anomalii este asociat\u0103 cu o anumit\u0103 gen\u0103; aceste trei gene sunt dispuse \u00een tandem pe bra\u0163ul scurt al cromozomului 11. Fenotipul variaz\u0103 \u00een func\u0163ie de m\u0103rimea dele\u0163iei. Statistic, 1:3 din copiii cu aniridie vor dezvolta tumora Wilms, \u00een timp ce doar 1:50 din copiii cu tumora Wilms asociaz\u0103 aniridie.<\/p>\n

Sindromul dele\u0163iei 22q11.2 ( Sindromul Shprintzen) include: Sindromul DiGeorge si Sindromul Velo-Cardio-Facial<\/em><\/p>\n

Reprezint\u0103 probabil cel mai frecvent sindrom cu microdele\u0163ii, dar adesea este dificil de identificat datorit\u0103 spectrului larg de manifestari clinice. Acest spectru include hipoplazia sau aplazia timusului (deficite imune) \u015fi a glandelor paratiroide (hipocalcemie), anomalii cardiace, dismorfie facial\u0103 sugestiv\u0103, despicatur\u0103 palatin\u0103 sau insuficien\u0163\u0103 velo-palatin\u0103, anomalii reno-urinare, anomalii scheletice, \u00eent\u00e2rziere \u00een dezvoltarea psihomotorie \u015fi tulbur\u0103ri psihice, dificult\u0103\u0163i de \u00eenv\u0103\u0163are \u015fi altele. P\u00e2n\u0103 la 15% din copii au un p\u0103rinte afectat de aceea\u015fi dele\u0163ie, dar cu un fenotip mult mai pu\u0163in sever. Se pare c\u0103 dele\u0163ia de 3Mb din por\u0163iunea proximal\u0103 a bra\u0163ului lung al cromozomului 22 (22q11.2q11.2) se datoreaz\u0103 recombin\u0103rii ce are loc \u00eentre secven\u0163ele repetitive ce flancheaza regiunea ce este \u00een mod obi\u015fnuit deletat\u0103. Aceste recombinari intracromozomiale vor genera o structur\u0103 \u00een form\u0103 de bucl\u0103 ce va fi detectat\u0103 ca un defect de c\u0103tre enzimele de reparare. Enzimele vor exciza ADN-ul din bucl\u0103 \u015fi vor reface por\u0163iunea linear\u0103 a cromozomului; va rezulta astfel o dele\u0163ie cu pierderea tuturor genelor asociate. Dele\u0163ia 22q11 este de obicei prea mic\u0103 pentru a fi identificat\u0103 prin examenul citogenetic de rutina \u00eens\u0103 poate fi demonstrat\u0103 prin tehnica FISH1;3<\/sup>.<\/p>\n

Recomand\u0103ri pentru determinarea cariotipului constitu\u0163ional<\/em><\/strong><\/p>\n

\u2013 \u00een scop de diagnostic la nou-n\u0103scu\u0163i sau copii mici ce prezint\u0103 semne sau simptome clinice sugestive pentru o anomalie cromozomial\u0103 (malforma\u0163ii congenitale multiple \u00eenso\u0163ite de tulbur\u0103ri de cre\u015ftere \u015fi retard psihomotor);<\/div>\n
<\/div>\n
\u00a0\u2013 persoane cu ambiguitate genital\u0103 (pentru stabilirea sexului genetic \u015fi identificarea unei anomalii a cromozomilor sexuali);<\/div>\n
<\/div>\n
\u00a0\u2013 pacien\u0163i cu retard mintal de cauz\u0103 neprecizat\u0103, mai ales dac\u0103 se asociaz\u0103 cu dismorfism\u00a0cranio-facial \u015fi cu o anamnez\u0103 familial\u0103 pozitiv\u0103;<\/div>\n
<\/div>\n
\u00a0\u2013 cupluri cu infertilitate, nou-n\u0103scu\u0163i mor\u0163i, nou-n\u0103scu\u0163i vii plurimalforma\u0163i sau avorturi spontane recurente (\u00een vederea depist\u0103rii unor anomalii cromozomiale echilibrate)1;3<\/sup>.<\/div>\n

Specimen recoltat<\/em><\/strong>\u00a0\u2013 s\u00e2nge venos4<\/sup>.<\/p>\n

Recipient de recoltare<\/em><\/strong>\u00a0\u2013 vacutainer ce con\u0163ine heparin\u0103 ca anticoagulant4<\/sup>.<\/sub><\/p>\n

Cantitate recoltat\u0103\u00a0<\/em><\/strong>\u2013 5 mL s\u00e2nge4<\/sup>.<\/p>\n

Cauze de respingere<\/em><\/strong>\u00a0a probei\u00a0<\/em><\/strong>\u2013 folosirea unui alt tip de anticoagulant; probe vechi, coagulate, hemolizate sau contaminate bacterian4<\/sup>.<\/p>\n

Stabilitate prob\u0103<\/em><\/strong>\u00a0\u2013 maxim\u00a072 ore<\/em>\u00a0din momentul recolt\u0103rii probei p\u00e2n\u0103 la intrarea acesteia \u00een lucru4<\/sup>.<\/p>\n

Metoda<\/em><\/strong>\u00a0\u2013\u00a0tehnica clasic\u0103 de bandare G; se va suplimenta cu testarea FISH \u00een func\u0163ie de suspiciunea clinic\u0103; sunt analizate 15 metafaze dintre care 5 sunt cariotipizate4<\/sup>.<\/p>\n

Raportarea \u015fi interpretarea rezultatelor<\/em><\/strong><\/p>\n

In vederea raport\u0103rii rezultatelor se va folosi urm\u0103toarea nomenclatur\u0103 pentru cariotip (\u00een conformitate cu ISCN = International System of Cytogenetic Nomenclature):<\/p>\n

\u2013 precizarea num\u0103rului total de cromozomi;<\/p>\n

\u2013 precizarea cromozomilor sexuali;<\/p>\n

\u2013 precizarea oric\u0103rei anomalii cromozomiale.<\/p>\n

Cele 3 tipuri de date sunt separate prin virgule.<\/p>\n

Exemple:<\/strong><\/p>\n

\u2022 Femeie cu cariotip normal: 46,XX;<\/p>\n

\u2022 B\u0103rbat cu cariotip normal: 46,XY;<\/p>\n

\u2022 Dac\u0103 sunt prezente dou\u0103 sau mai multe linii celulare (mosaicism sau chimerism)\u00a0acestea vor fi indicate secven\u0163ial \u015fi separate prin semnul \/ iar clona diploid\u0103 normal\u0103 (dac\u0103 exist\u0103) va fi men\u0163ionat\u0103 ultima: 45,X\/46,XX; alte clone vor fi prezentate \u00een ordinea dimensiunii acestora, clona cea mai mare fiind prima men\u0163ionat\u0103 \u2013 num\u0103rul de celule din fiecare clon\u0103 va fi indicat de un num\u0103r trecut \u00een parantez\u0103: 45,X(15)\/47,XXX(3)\/46,XX(12);<\/p>\n

\u2022 In cazul anomaliilor numerice autozomale, num\u0103rul total de cromozomi va fi crescut sau redus pentru a indica modificarea global\u0103, iar cromozomul specific dob\u00e2ndit sau pierdut va fi precizat la sf\u00e2r\u015fit: 47,XX,+13 (trisomie 13 la o persoan\u0103 de sex feminin); 45,XY,-8 (monosomie 8 la o persoan\u0103 de sex masculin);<\/p>\n

\u2022 In cazul anomaliilor numerice constitu\u0163ionale ale cromozomilor sexuali, nu vor mai fi folosite semnele + sau -: 45,X; 47,XXX; 47,XXY, 47,XYY; pe de alt\u0103 parte dac\u0103 anomaliile numerice ale cromozomilor sexuali sunt dob\u00e2ndite \u00een unele linii celulare maligne vor fi folosite semnele + sau -: 45,X,-Y (o persoan\u0103 de sex masculin care a pierdut cromozomul Y ca rezultat al unei afec\u0163iuni maligne);<\/p>\n

\u2022 Dac\u0103 sunt prezente, anomaliile cromozomiale structurale vor fi indicate la sf\u00e2r\u015fitul nomenclaturii pentru a clarifica statusul cromozomului rearanjat; vor fi folosite abrevieri ale anomaliei urmate de cromozomul implicat \u015fi de punctele de ruptur\u0103 corespunzatoare:<\/p>\n

\u2013 46,XX,del(4)(p15): dele\u0163ia terminal\u0103 a bra\u0163ului scurt al cromozomului 4, la banda 15;<\/p>\n

\u2013 46,XX,dup(11)(q13q23): duplica\u0163ia intersti\u0163ial\u0103 a bra\u0163ului lung al cromozomului 11;<\/p>\n

\u2013 46,XY,t(4;9)(q21.2;p22): transloca\u0163ie \u00eentre bra\u0163ul lung al cromozomului 4 \u015fi bra\u0163ul scurt al cromozomului 9;<\/p>\n

\u2013\u00a0 46,XY,inv(9)(p11q21.1): inversie pericentric\u0103 la nivelul cromozomului 9 \u00eentre benzile p11 \u015fi q21.1.<\/p>\n

La buletinul final va fi ata\u015fat\u0103 \u015fi cariograma pacientului respectiv1;4<\/sup>.<\/p>\n

\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/strong><\/p>\n

1. Constance K. Stein. Applications of Cytogenetics in Modern Pathology. In Henry\u2019s Clinical Diagnosis and Management by Laboratory Methods- Sauders Elsevier 21-Ed 2007, 1267-1281.<\/p>\n

2. Chromosome Abnormality. www.web-books.com. Reference Type: Internet Communication.<\/p>\n

3. Eberhard Passarge. Karyotype-Phenotype Relationship. In Color Atlas of Genetics, Georg Thieme Verlag KG, 3rd Edition, 2007, 412-416.<\/p>\n

4. Laborator Synevo. Referin\u0163ele specifice tehnologiei de lucru utilizate 2010. Ref Type: Catalog.<\/p>","protected":false},"excerpt":{"rendered":"

\u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 \u2013 \u0446\u0438\u0442\u043e\u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435, \u0438\u0437\u0443\u0447\u0435\u043d\u0438\u0435 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u043e\u0433\u043e \u043d\u0430\u0431\u043e\u0440\u0430 \u0447\u0435\u043b\u043e\u0432\u0435\u043a\u0430, \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u044e\u0449\u0435\u0435 \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0438\u0442\u044c \u043e\u0442\u043a\u043b\u043e\u043d\u0435\u043d\u0438\u044f \u0432 \u0441\u0442\u0440\u0443\u043a\u0442\u0443\u0440\u0435 \u0438 \u0447\u0438\u0441\u043b\u0435 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c.\u00a0\u041e\u043d\u043e \u043f\u043e\u043c\u043e\u0433\u0430\u0435\u0442 \u0432\u044b\u044f\u0432\u0438\u0442\u044c \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u0432\u0435\u0440\u043e\u044f\u0442\u043d\u043e, \u043d\u0435 \u0432\u043b\u0438\u044f\u044e\u0449\u0438\u0435 \u043d\u0430 \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u0435 \u0447\u0435\u043b\u043e\u0432\u0435\u043a\u0430, \u043d\u043e \u0442\u0435\u043c \u043d\u0435 \u043c\u0435\u043d\u0435\u0435 \u0432\u0430\u0436\u043d\u044b\u0435 \u0434\u043b\u044f \u043f\u043b\u0430\u043d\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u044f \u0431\u0443\u0434\u0443\u0449\u0435\u0439 \u0431\u0435\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u0438 \u0434\u043b\u044f \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u044f \u0431\u0443\u0434\u0443\u0449\u0435\u0433\u043e \u0440\u0435\u0431\u0435\u043d\u043a\u0430 (\u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0438 \u043f\u043b\u043e\u0434\u0430, \u0430\u043d\u043e\u043c\u0430\u043b\u0438\u0438 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f).<\/em><\/p>\n

\u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f \u2013 \u044d\u0442\u043e \u043f\u043e\u043b\u043d\u044b\u0439 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u044b\u0439 \u043d\u0430\u0431\u043e\u0440 \u043a\u043b\u0435\u0442\u043a\u0438 \u0447\u0435\u043b\u043e\u0432\u0435\u043a\u0430. \u0412 \u043d\u043e\u0440\u043c\u0435 \u043e\u043d \u0441\u043e\u0441\u0442\u043e\u0438\u0442 \u0438\u0437 46 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u0438\u0437 \u043d\u0438\u0445 44 \u0430\u0443\u0442\u043e\u0441\u043e\u043c\u044b (22 \u043f\u0430\u0440\u044b), \u0438\u043c\u0435\u044e\u0449\u0438\u0445 \u043e\u0434\u0438\u043d\u0430\u043a\u043e\u0432\u043e\u0435 \u0441\u0442\u0440\u043e\u0435\u043d\u0438\u0435 \u0438 \u0432 \u043c\u0443\u0436\u0441\u043a\u043e\u043c, \u0438 \u0432 \u0436\u0435\u043d\u0441\u043a\u043e\u043c \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c\u0435, \u0438 \u043e\u0434\u043d\u0430 \u043f\u0430\u0440\u0430 \u043f\u043e\u043b\u043e\u0432\u044b\u0445 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c (XY \u0443 \u043c\u0443\u0436\u0447\u0438\u043d \u0438 XX \u0443 \u0436\u0435\u043d\u0449\u0438\u043d). \u041a\u0430\u0436\u0434\u0430\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u0430 \u043d\u0435\u0441\u0435\u0442 \u0433\u0435\u043d\u044b, \u043e\u0442\u0432\u0435\u0442\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u0435 \u0437\u0430 \u043d\u0430\u0441\u043b\u0435\u0434\u0441\u0442\u0432\u0435\u043d\u043d\u043e\u0441\u0442\u044c. \u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f 46, \u0425\u0425 \u2013 \u0441\u043e\u043e\u0442\u0432\u0435\u0442\u0441\u0442\u0432\u0443\u0435\u0442 \u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u043e\u043c\u0443 \u0436\u0435\u043d\u0441\u043a\u043e\u043c\u0443 \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0443, \u0430 \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f 46, XY \u2013 \u044d\u0442\u043e \u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u0439 \u043c\u0443\u0436\u0441\u043a\u043e\u0439 \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f. \u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f \u043e\u0441\u0442\u0430\u0435\u0442\u0441\u044f \u043d\u0435\u0438\u0437\u043c\u0435\u043d\u043d\u044b\u043c \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 \u0432\u0441\u0435\u0439 \u0436\u0438\u0437\u043d\u0438.<\/p>\n

\u041d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u043e\u0433\u043e \u043d\u0430\u0431\u043e\u0440\u0430 \u043c\u043e\u0433\u0443\u0442 \u044f\u0432\u043b\u044f\u0442\u044c\u0441\u044f \u043f\u0440\u0438\u0447\u0438\u043d\u043e\u0439 \u043d\u0430\u0441\u043b\u0435\u0434\u0441\u0442\u0432\u0435\u043d\u043d\u043e\u0439 \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0438, \u0431\u0435\u0441\u043f\u043b\u043e\u0434\u0438\u044f, \u043d\u0435\u0432\u044b\u043d\u0430\u0448\u0438\u0432\u0430\u043d\u0438\u044f \u0431\u0435\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0441\u0442\u0438, \u0440\u043e\u0436\u0434\u0435\u043d\u0438\u044f \u0440\u0435\u0431\u0435\u043d\u043a\u0430 \u0441 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u043c\u0438 \u043f\u043e\u0440\u043e\u043a\u0430\u043c\u0438 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f.<\/p>\n

\u0414\u043b\u044f \u0446\u0438\u0442\u043e\u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u0447\u0430\u0449\u0435 \u0432\u0441\u0435\u0433\u043e \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u044e\u0442 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u044b \u043a\u0440\u0430\u0442\u043a\u043e\u0432\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0439 \u043a\u0443\u043b\u044c\u0442\u0443\u0440\u044b \u043a\u0440\u043e\u0432\u0438, \u0440\u0435\u0436\u0435 \u043a\u043b\u0435\u0442\u043a\u0438 \u043a\u043e\u0441\u0442\u043d\u043e\u0433\u043e \u043c\u043e\u0437\u0433\u0430 \u0438 \u043a\u0443\u043b\u044c\u0442\u0443\u0440\u044b \u0444\u0438\u0431\u0440\u043e\u0431\u043b\u0430\u0441\u0442\u043e\u0432.<\/p>\n

\u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 \u043a\u0443\u043b\u044c\u0442\u0443\u0440\u044b \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432 \u043f\u0435\u0440\u0438\u0444\u0435\u0440\u0438\u0447\u0435\u0441\u043a\u043e\u0439 \u043a\u0440\u043e\u0432\u0438 \u0447\u0435\u043b\u043e\u0432\u0435\u043a\u0430 \u2013 \u0441\u043b\u043e\u0436\u043d\u043e\u0435 \u043c\u043d\u043e\u0433\u043e\u0441\u0442\u0443\u043f\u0435\u043d\u0447\u0430\u0442\u043e\u0435 \u0446\u0438\u0442\u043e\u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435, \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u0441\u044f, \u043a\u043e\u0433\u0434\u0430 \u043a\u043b\u0435\u0442\u043a\u0438 \u0432\u0445\u043e\u0434\u044f\u0442 \u0432 \u0444\u0430\u0437\u0443 \u043c\u0438\u0442\u043e\u0437\u0430 \u2013 \u043d\u0435\u043f\u0440\u044f\u043c\u043e\u0433\u043e \u0434\u0435\u043b\u0435\u043d\u0438\u044f \u0441 \u0442\u043e\u0436\u0434\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u043c \u0440\u0430\u0441\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u0435\u043c \u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u043c\u0430\u0442\u0435\u0440\u0438\u0430\u043b\u0430 \u043c\u0435\u0436\u0434\u0443 \u0434\u043e\u0447\u0435\u0440\u043d\u0438\u043c\u0438 \u043a\u043b\u0435\u0442\u043a\u0430\u043c\u0438. \u041e\u043d\u043e \u0432\u043a\u043b\u044e\u0447\u0430\u0435\u0442 \u0432 \u0441\u0435\u0431\u044f \u0441\u043b\u0435\u0434\u0443\u044e\u0449\u0438\u0435 \u044d\u0442\u0430\u043f\u044b:<\/p>\n

    \n
  • \u041f\u043e\u0441\u0442\u0430\u043d\u043e\u0432\u043a\u0430 \u043a\u0443\u043b\u044c\u0442\u0443\u0440\u044b \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432, \u0440\u043e\u0441\u0442 \u043a\u043b\u0435\u0442\u043e\u043a \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 72 \u0447\u0430\u0441\u043e\u0432. (\u0420\u043e\u0441\u0442 \u043a\u043b\u0435\u0442\u043e\u043a \u043c\u043e\u0436\u0435\u0442 \u0431\u044b\u0442\u044c \u043e\u0441\u043b\u043e\u0436\u043d\u0435\u043d \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u044b\u043c\u0438 \u0444\u0430\u043a\u0442\u043e\u0440\u0430\u043c\u0438: \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u043e\u043d\u043d\u044b\u0445, \u0445\u0440\u043e\u043d\u0438\u0447\u0435\u0441\u043a\u0438\u0445, \u043f\u0440\u043e\u0441\u0442\u0443\u0434\u043d\u044b\u0445 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0439; \u043f\u0440\u0438\u0435\u043c \u043b\u0435\u043a\u0430\u0440\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432; \u0434\u0438\u0435\u0442\u0430; \u043f\u0440\u0438\u0435\u043c \u0430\u043b\u043a\u043e\u0433\u043e\u043b\u044f \u0438 \u0442.\u00a0\u043f. \u0412\u0441\u0435 \u044d\u0442\u0438 \u0444\u0430\u043a\u0442\u043e\u0440\u044b \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c\u043e \u0438\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u044c \u043f\u0435\u0440\u0435\u0434 \u0441\u0434\u0430\u0447\u0435\u0439 \u0430\u043d\u0430\u043b\u0438\u0437\u043e\u0432).<\/li>\n
  • \u041e\u0431\u0440\u0430\u0431\u043e\u0442\u043a\u0430 \u043a\u0443\u043b\u044c\u0442\u0443\u0440 \u043b\u0438\u043c\u0444\u043e\u0446\u0438\u0442\u043e\u0432: \u043a\u043e\u043b\u0445\u0438\u0446\u0438\u043d\u0438\u0437\u0430\u0446\u0438\u044f, \u0433\u0438\u043f\u043e\u0442\u043e\u043d\u0438\u0437\u0430\u0446\u0438\u044f, \u0444\u0438\u043a\u0441\u0430\u0446\u0438\u044f.<\/li>\n
  • \u041f\u0440\u0438\u0433\u043e\u0442\u043e\u0432\u043b\u0435\u043d\u0438\u0435 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u043d\u0430 \u0441\u0442\u0435\u043a\u043b\u0435.<\/li>\n
  • \u041c\u043e\u043d\u043e\u0445\u0440\u043e\u043c\u043d\u043e\u0435 \u0438 \u0434\u0438\u0444\u0444\u0435\u0440\u0435\u043d\u0446\u0438\u0430\u043b\u044c\u043d\u043e\u0435 \u043e\u043a\u0440\u0430\u0448\u0438\u0432\u0430\u043d\u0438\u0435 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u0430.<\/li>\n
  • \u0410\u043d\u0430\u043b\u0438\u0437 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432 (\u043f\u043e\u0434\u0441\u0447\u0438\u0442\u044b\u0432\u0430\u0435\u0442\u0441\u044f\u00a0 \u043e\u0431\u0449\u0435\u0435 \u043a\u043e\u043b\u0438\u0447\u0435\u0441\u0442\u0432\u043e \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u0441\u044f \u043e\u0446\u0435\u043d\u043a\u0430 \u0441\u0442\u0440\u0443\u043a\u0442\u0443\u0440\u044b \u043a\u0430\u0436\u0434\u043e\u0439 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b). \u0410\u043d\u0430\u043b\u0438\u0437 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u043e\u0441\u0443\u0449\u0435\u0441\u0442\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043d\u0430 \u0440\u0430\u0437\u0440\u0435\u0448\u0435\u043d\u0438\u0438 \u0432 400-500 \u043f\u043e\u043b\u043e\u0441 (\u0431\u044d\u043d\u0434\u043e\u0432).<\/li>\n<\/ul>\n

    \u0420\u0430\u0437\u043b\u0438\u0447\u0430\u044e\u0442 \u043d\u0435\u0441\u043a\u043e\u043b\u044c\u043a\u043e \u0432\u0438\u0434\u043e\u0432 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0439 \u0441\u0442\u0440\u0443\u043a\u0442\u0443\u0440\u044b \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c:<\/p>\n

      \n
    • \u00a0 \u0442\u0440\u0438\u0441\u043e\u043c\u0438\u0438 \u2013 \u0434\u043e\u0431\u0430\u0432\u043b\u0435\u043d\u0438\u0435 \u0435\u0449\u0435 \u043e\u0434\u043d\u043e\u0439 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b \u043a \u043f\u0430\u0440\u0435;<\/li>\n
    • \u00a0 \u043c\u043e\u043d\u043e\u0441\u043e\u043c\u0438\u0438 \u2013 \u0443\u0442\u0440\u0430\u0442\u0430 \u043e\u0434\u043d\u043e\u0439 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b \u0438\u0437 \u043f\u0430\u0440\u044b;<\/li>\n
    • \u00a0 \u0434\u0435\u043b\u0435\u0446\u0438\u0438 \u2013 \u0443\u0442\u0440\u0430\u0442\u0430 \u0443\u0447\u0430\u0441\u0442\u043a\u0430 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b;<\/li>\n
    • \u00a0 \u0434\u0443\u043f\u043b\u0438\u043a\u0430\u0446\u0438\u0438 \u2013 \u043f\u043e\u0432\u0442\u043e\u0440\u0435\u043d\u0438\u0435 \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043d\u043e\u0433\u043e \u0443\u0447\u0430\u0441\u0442\u043a\u0430 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b;<\/li>\n
    • \u00a0 \u0438\u043d\u0432\u0435\u0440\u0441\u0438\u0438 \u2013 \u043f\u043e\u0432\u043e\u0440\u043e\u0442 \u0443\u0447\u0430\u0441\u0442\u043a\u0430 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b \u043d\u0430 180 \u0433\u0440\u0430\u0434\u0443\u0441\u043e\u0432;<\/li>\n
    • \u00a0 \u0442\u0440\u0430\u043d\u0441\u043b\u043e\u043a\u0430\u0446\u0438\u0438 \u2013 \u043f\u0435\u0440\u0435\u043d\u043e\u0441 \u0443\u0447\u0430\u0441\u0442\u043a\u043e\u0432 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b \u0432 \u043d\u043e\u0432\u043e\u0435 \u043f\u043e\u043b\u043e\u0436\u0435\u043d\u0438\u0435.<\/li>\n<\/ul>\n

      \u0425\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u044b\u0435 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f\u0440\u0430\u0437\u043b\u0438\u0447\u0430\u044e\u0442\u0441\u044f \u0442\u0430\u043a\u0436\u0435 \u043f\u043e \u043f\u0440\u0438\u043d\u0446\u0438\u043f\u0443 \u0440\u0435\u0433\u0443\u043b\u044f\u0440\u043d\u043e\u0441\u0442\u0438. \u0420\u0435\u0433\u0443\u043b\u044f\u0440\u043d\u044b\u0435 \u043c\u0443\u0442\u0430\u0446\u0438\u0438 \u043f\u0440\u0438\u0441\u0443\u0442\u0441\u0442\u0432\u0443\u044e\u0442 \u043f\u0440\u0438 \u0434\u0435\u043b\u0435\u043d\u0438\u0438 \u043a\u0430\u0436\u0434\u043e\u0439 \u043a\u043b\u0435\u0442\u043a\u0438 \u0438\u043b\u0438 \u0431\u043e\u043b\u044c\u0448\u0438\u043d\u0441\u0442\u0432\u0430 \u043a\u043b\u0435\u0442\u043e\u043a. \u041e\u043d\u0438 \u043f\u0440\u043e\u044f\u0432\u043b\u044f\u044e\u0442\u0441\u044f \u0432 \u043c\u043e\u043c\u0435\u043d\u0442 \u0437\u0430\u0447\u0430\u0442\u0438\u044f \u043f\u043b\u043e\u0434\u0430 \u043b\u0438\u0431\u043e \u0432 \u043f\u0435\u0440\u0432\u044b\u0435 \u043d\u0435\u0441\u043a\u043e\u043b\u044c\u043a\u043e \u0434\u043d\u0435\u0439 \u0431\u0435\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0441\u0442\u0438. \u041d\u0435\u0440\u0435\u0433\u0443\u043b\u044f\u0440\u043d\u044b\u0435 \u0430\u0431\u0435\u0440\u0440\u0430\u0446\u0438\u0438 \u043f\u043e\u044f\u0432\u043b\u044f\u044e\u0442\u0441\u044f \u0432 \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u0435 \u043d\u0435\u0433\u0430\u0442\u0438\u0432\u043d\u043e\u0433\u043e \u0432\u043e\u0437\u0434\u0435\u0439\u0441\u0442\u0432\u0438\u044f \u0440\u0430\u0434\u0438\u0430\u0446\u0438\u0438, \u0445\u0438\u043c\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u0441\u0440\u0435\u0434\u0441\u0442\u0432 \u0438 \u0442.\u0434.<\/p>\n

      \u041d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435 \u0440\u0430\u0441\u0445\u043e\u0436\u0434\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u043c\u043e\u0436\u0435\u0442 \u043f\u0440\u043e\u0438\u0437\u043e\u0439\u0442\u0438 \u0432\u043e \u0432\u0440\u0435\u043c\u044f \u043a\u043b\u0435\u0442\u043e\u0447\u043d\u043e\u0433\u043e \u0434\u0435\u043b\u0435\u043d\u0438\u044f (\u043c\u0435\u0439\u043e\u0437\u0430). \u0415\u0441\u043b\u0438 \u0442\u0430\u043a\u043e\u0435 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435 \u043f\u0440\u043e\u0438\u0441\u0445\u043e\u0434\u0438\u0442 \u0432 \u043f\u0440\u043e\u0446\u0435\u0441\u0441\u0435 \u043e\u0431\u0440\u0430\u0437\u043e\u0432\u0430\u043d\u0438\u044f \u0441\u043f\u0435\u0440\u043c\u0430\u0442\u043e\u0437\u043e\u0438\u0434\u043e\u0432 \u0438\u043b\u0438 \u044f\u0439\u0446\u0435\u043a\u043b\u0435\u0442\u043e\u043a, \u0442\u043e \u0432 \u043f\u043e\u043b\u043e\u0432\u043e\u0439 \u043a\u043b\u0435\u0442\u043a\u0435 \u043f\u043e\u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043b\u0438\u0448\u043d\u044f\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u0430, \u043a\u043e\u0442\u043e\u0440\u0430\u044f \u043f\u0440\u0438 \u0437\u0430\u0447\u0430\u0442\u0438\u0438 \u0431\u0443\u0434\u0435\u0442 \u043f\u0435\u0440\u0435\u0434\u0430\u043d\u0430 \u0440\u0435\u0431\u0435\u043d\u043a\u0443. \u0412 \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u0435 \u043e\u043d\u0430 \u0431\u0443\u0434\u0435\u0442 \u043f\u0440\u0438\u0441\u0443\u0442\u0441\u0442\u0432\u043e\u0432\u0430\u0442\u044c \u0432\u043e \u0432\u0441\u0435\u0445 \u043a\u043b\u0435\u0442\u043a\u0430\u0445 \u043e\u0440\u0433\u0430\u043d\u0438\u0437\u043c\u0430 \u0440\u0435\u0431\u0435\u043d\u043a\u0430. \u041f\u0440\u0438\u043c\u0435\u0440\u043e\u043c \u0442\u0440\u0438\u0441\u043e\u043c\u0438\u0438 \u043c\u043e\u0436\u0435\u0442 \u0441\u043b\u0443\u0436\u0438\u0442\u044c \u0441\u0438\u043d\u0434\u0440\u043e\u043c \u0414\u0430\u0443\u043d\u0430 (\u043b\u0438\u0448\u043d\u044f\u044f 21-\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u0430) \u0438\u043b\u0438 \u0441\u0438\u043d\u0434\u0440\u043e\u043c \u041f\u0430\u0442\u0430\u0443 (\u0442\u0440\u0438\u0441\u043e\u043c\u0438\u044f 13-\u0439 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b). \u0422\u0430\u043a\u0436\u0435 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435 \u0440\u0430\u0441\u0445\u043e\u0436\u0434\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u043c\u043e\u0436\u0435\u0442 \u043f\u0440\u043e\u0438\u0437\u043e\u0439\u0442\u0438 \u043f\u0440\u0438 \u043f\u0435\u0440\u0432\u044b\u0445 \u0434\u0435\u043b\u0435\u043d\u0438\u044f\u0445 \u043e\u043f\u043b\u043e\u0434\u043e\u0442\u0432\u043e\u0440\u0435\u043d\u043d\u043e\u0439 \u044f\u0439\u0446\u0435\u043a\u043b\u0435\u0442\u043a\u0438. \u041d\u0430\u043f\u0440\u0438\u043c\u0435\u0440, \u0443\u0442\u0440\u0430\u0442\u0430 \u0425-\u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b \u043f\u0440\u0438\u0432\u043e\u0434\u0438\u0442 \u043a \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044e \u04250-\u0441\u0438\u043d\u0434\u0440\u043e\u043c\u0430, \u0438\u043b\u0438 \u0441\u0438\u043d\u0434\u0440\u043e\u043c\u0430 \u0428\u0435\u0440\u0435\u0448\u0435\u0432\u0441\u043a\u043e\u0433\u043e \u2013 \u0422\u0435\u0440\u043d\u0435\u0440\u0430. \u0410\u043d\u043e\u043c\u0430\u043b\u0438\u0438, \u0441\u0432\u044f\u0437\u0430\u043d\u043d\u044b\u0435 \u0441 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435\u043c \u0440\u0430\u0441\u0445\u043e\u0436\u0434\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u0432\u0441\u0442\u0440\u0435\u0447\u0430\u044e\u0442\u0441\u044f \u043d\u0435 \u0442\u0430\u043a \u0447\u0430\u0441\u0442\u043e, \u043f\u043e\u044d\u0442\u043e\u043c\u0443 \u0432\u0435\u0440\u043e\u044f\u0442\u043d\u043e\u0441\u0442\u044c \u0438\u0445 \u043f\u043e\u0432\u0442\u043e\u0440\u0435\u043d\u0438\u044f \u0432 \u043e\u0434\u043d\u043e\u0439 \u0438 \u0442\u043e\u0439 \u0436\u0435 \u0441\u0435\u043c\u044c\u0435 \u0434\u043e\u0441\u0442\u0430\u0442\u043e\u0447\u043d\u043e \u043c\u0430\u043b\u0430.<\/p>\n

      \u0421\u0442\u0440\u0443\u043a\u0442\u0443\u0440\u043d\u044b\u0435 \u0436\u0435 \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u044f \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c \u043f\u0435\u0440\u0435\u0434\u0430\u044e\u0442\u0441\u044f \u043f\u043e \u043d\u0430\u0441\u043b\u0435\u0434\u0441\u0442\u0432\u0443, \u043f\u0440\u0438 \u044d\u0442\u043e\u043c \u0441\u0442\u0435\u043f\u0435\u043d\u044c \u0441\u0435\u043c\u0435\u0439\u043d\u043e\u0433\u043e \u0440\u0438\u0441\u043a\u0430 \u0438 \u0434\u0430\u043b\u044c\u043d\u0435\u0439\u0448\u0430\u044f \u043f\u0435\u0440\u0435\u0434\u0430\u0447\u0430 \u0434\u0435\u0444\u0435\u043a\u0442\u0430 \u043e\u0442 \u043f\u043e\u043a\u043e\u043b\u0435\u043d\u0438\u044f \u043a \u043f\u043e\u043a\u043e\u043b\u0435\u043d\u0438\u044e \u0441\u0442\u0430\u043d\u043e\u0432\u0438\u0442\u0441\u044f \u0437\u043d\u0430\u0447\u0438\u0442\u0435\u043b\u044c\u043d\u043e \u0432\u044b\u0441\u043e\u043a\u043e\u0439.<\/p>\n

      \u041a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 \u0442\u0430\u043a\u0436\u0435 \u0440\u0435\u043a\u043e\u043c\u0435\u043d\u0434\u0443\u044e\u0442 \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u044c \u0432 \u0442\u0435\u0445 \u0441\u0435\u043c\u044c\u044f\u0445, \u0433\u0434\u0435 \u0435\u0441\u0442\u044c \u0432\u044b\u0441\u043e\u043a\u0430\u044f \u0432\u0435\u0440\u043e\u044f\u0442\u043d\u043e\u0441\u0442\u044c \u0440\u043e\u0436\u0434\u0435\u043d\u0438\u044f \u0440\u0435\u0431\u0435\u043d\u043a\u0430 \u0441 \u0431\u043e\u043b\u0435\u0437\u043d\u044c\u044e, \u0441\u0446\u0435\u043f\u043b\u0435\u043d\u043d\u043e\u0439 \u0441 \u0425-\u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043e\u0439.<\/p>\n

      \u041a\u043e\u0433\u0434\u0430 \u043d\u0430\u0437\u043d\u0430\u0447\u0430\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?<\/strong><\/p>\n

      \u041f\u043e\u043a\u0430\u0437\u0430\u043d\u0438\u044f \u0434\u043b\u044f \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u044f \u0441\u0443\u043f\u0440\u0443\u0436\u0435\u0441\u043a\u0438\u0445 \u043f\u0430\u0440:<\/p>\n

        \n
      • \u043c\u0443\u0436\u0441\u043a\u043e\u0435 \u0431\u0435\u0441\u043f\u043b\u043e\u0434\u0438\u0435: \u0442\u044f\u0436\u0435\u043b\u0430\u044f \u043e\u043b\u0438\u0433\u043e\u0437\u043e\u043e\u0441\u043f\u0435\u0440\u043c\u0438\u044f, \u043d\u0435\u043e\u0431\u0441\u0442\u0440\u0443\u043a\u0442\u0438\u0432\u043d\u0430\u044f \u0430\u0437\u043e\u043e\u0441\u043f\u0435\u0440\u043c\u0438\u044f, \u0442\u0435\u0440\u0430\u0442\u043e\u0437\u043e\u043e\u0441\u043f\u0435\u0440\u043c\u0438\u044f;<\/li>\n
      • \u043f\u0435\u0440\u0432\u0438\u0447\u043d\u0430\u044f \u0430\u043c\u0435\u043d\u043e\u0440\u0435\u044f;<\/li>\n
      • \u043f\u0440\u0438\u0432\u044b\u0447\u043d\u043e\u0435 \u043d\u0435\u0432\u044b\u043d\u0430\u0448\u0438\u0432\u0430\u043d\u0438\u0435 \u0431\u0435\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u0432 \u043f\u0435\u0440\u0432\u043e\u043c \u0442\u0440\u0438\u043c\u0435\u0441\u0442\u0440\u0435 (2 \u0438 \u0431\u043e\u043b\u0435\u0435 \u0432\u044b\u043a\u0438\u0434\u044b\u0448\u0435\u0439);<\/li>\n
      • \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u0432\u044b\u043a\u0438\u0434\u044b\u0448\u0435\u0439 \u043d\u0435\u044f\u0441\u043d\u043e\u0433\u043e \u0433\u0435\u043d\u0435\u0437\u0430 \u0432 \u0430\u043d\u0430\u043c\u043d\u0435\u0437\u0435;<\/li>\n
      • \u0441\u043b\u0443\u0447\u0430\u0438 \u043c\u0435\u0440\u0442\u0432\u043e\u0440\u043e\u0436\u0434\u0435\u043d\u0438\u0439 \u0432 \u0430\u043d\u0430\u043c\u043d\u0435\u0437\u0435;<\/li>\n
      • \u0441\u043b\u0443\u0447\u0430\u0438 \u0440\u0430\u043d\u043d\u0435\u0439 \u043c\u043b\u0430\u0434\u0435\u043d\u0447\u0435\u0441\u043a\u043e\u0439 \u0441\u043c\u0435\u0440\u0442\u043d\u043e\u0441\u0442\u0438 \u0432 \u0430\u043d\u0430\u043c\u043d\u0435\u0437\u0435;<\/li>\n
      • \u0440\u043e\u0436\u0434\u0435\u043d\u0438\u0435 \u0434\u0435\u0442\u0435\u0439 \u0441 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u043d\u043e\u0439 \u0430\u043d\u043e\u043c\u0430\u043b\u0438\u0435\u0439 (\u043d\u0430\u043f\u0440\u0438\u043c\u0435\u0440, \u0441\u0438\u043d\u0434\u0440\u043e\u043c\u043e\u043c \u0414\u0430\u0443\u043d\u0430);<\/li>\n
      • \u0440\u043e\u0436\u0434\u0435\u043d\u0438\u0435 \u0434\u0435\u0442\u0435\u0439 \u0441 \u043c\u043d\u043e\u0436\u0435\u0441\u0442\u0432\u0435\u043d\u043d\u044b\u043c\u0438 \u0432\u0440\u043e\u0436\u0434\u0451\u043d\u043d\u044b\u043c\u0438 \u043f\u043e\u0440\u043e\u043a\u0430\u043c\u0438 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f (\u041c\u0412\u041f\u0420);<\/li>\n
      • \u043f\u043b\u0430\u043d\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u0435 \u042d\u041a\u041e;<\/li>\n
      • \u043d\u0435\u0443\u0434\u0430\u0447\u043d\u044b\u0435 \u043f\u043e\u043f\u044b\u0442\u043a\u0438 \u042d\u041a\u041e;<\/li>\n
      • \u043f\u0440\u043e\u0433\u043d\u043e\u0437 \u0437\u0434\u043e\u0440\u043e\u0432\u044c\u044f \u0431\u0443\u0434\u0443\u0449\u0435\u0433\u043e \u0440\u0435\u0431\u0435\u043d\u043a\u0430.<\/li>\n<\/ul>\n

        \u041f\u043e\u043a\u0430\u0437\u0430\u043d\u0438\u044f \u0434\u043b\u044f \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0438\u0440\u043e\u0432\u0430\u043d\u0438\u044f \u0434\u0435\u0442\u0435\u0439:<\/p>\n

          \n
        • \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u0432\u0440\u043e\u0436\u0434\u0451\u043d\u043d\u044b\u0445 \u043f\u043e\u0440\u043e\u043a\u043e\u0432 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f;<\/li>\n
        • \u0443\u043c\u0441\u0442\u0432\u0435\u043d\u043d\u0430\u044f \u043e\u0442\u0441\u0442\u0430\u043b\u043e\u0441\u0442\u044c;<\/li>\n
        • \u0437\u0430\u0434\u0435\u0440\u0436\u043a\u0430 \u043f\u0441\u0438\u0445\u043e\u043c\u043e\u0442\u043e\u0440\u043d\u043e\u0433\u043e \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f;<\/li>\n
        • \u0437\u0430\u0434\u0435\u0440\u0436\u043a\u0430 \u043f\u0441\u0438\u0445\u043e-\u0440\u0435\u0447\u0435\u0432\u043e\u0433\u043e \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f \u0432 \u0441\u043e\u0447\u0435\u0442\u0430\u043d\u0438\u0438 \u0441 \u043c\u0438\u043a\u0440\u043e\u0430\u043d\u043e\u043c\u0430\u043b\u0438\u044f\u043c\u0438;<\/li>\n
        • \u043d\u0430\u0440\u0443\u0448\u0435\u043d\u0438\u0435 \u0438\u043b\u0438 \u0437\u0430\u0434\u0435\u0440\u0436\u043a\u0430 \u043f\u043e\u043b\u043e\u0432\u043e\u0433\u043e \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f;<\/li>\n
        • \u0437\u0430\u0434\u0435\u0440\u0436\u043a\u0430 \u0440\u043e\u0441\u0442\u0430;<\/li>\n
        • \u0430\u043d\u043e\u043c\u0430\u043b\u0438\u0438 \u043f\u043e\u043b\u0430.<\/li>\n<\/ul>\n

          \u0427\u0442\u043e \u043e\u0437\u043d\u0430\u0447\u0430\u044e\u0442 \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u044b?<\/strong><\/p>\n

          \u0414\u043b\u044f\u00a0\u043c\u0443\u0436\u0447\u0438\u043d<\/strong>\u00a0\u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u043c \u0441\u0447\u0438\u0442\u0430\u0435\u0442\u0441\u044f \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u00a046,XY. \u042d\u0442\u043e \u043e\u0437\u043d\u0430\u0447\u0430\u0435\u0442, \u0447\u0442\u043e \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043e 46 \u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u0445 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u0432 \u0442\u043e\u043c \u0447\u0438\u0441\u043b\u0435 X \u0438 Y \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u0430.<\/p>\n

          \u0414\u043b\u044f\u00a0\u0436\u0435\u043d\u0449\u0438\u043d\u00a0<\/strong>\u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u043c \u0441\u0447\u0438\u0442\u0430\u0435\u0442\u0441\u044f \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u00a046,XX. \u042d\u0442\u043e \u043e\u0437\u043d\u0430\u0447\u0430\u0435\u0442, \u0447\u0442\u043e \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043e 46 \u043d\u043e\u0440\u043c\u0430\u043b\u044c\u043d\u044b\u0445 \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c, \u0432 \u0442\u043e\u043c \u0447\u0438\u0441\u043b\u0435 \u0434\u0432\u0435 X \u0445\u0440\u043e\u043c\u043e\u0441\u043e\u043c\u044b.<\/p>\n

          \u0412 \u0441\u043b\u0443\u0447\u0430\u0435 \u0432\u044b\u044f\u0432\u043b\u0435\u043d\u0438\u044f \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u043e\u0433\u043e \u043a\u0430\u0440\u0438\u043e\u0442\u0438\u043f\u0430, \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c\u0430 \u043a\u043e\u043d\u0441\u0443\u043b\u044c\u0442\u0430\u0446\u0438\u044f \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0441\u043a\u043e\u0433\u043e \u0433\u0435\u043d\u0435\u0442\u0438\u043a\u0430 \u043f\u043e \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u0430\u043c \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f \u0434\u043b\u044f \u043f\u0440\u0430\u0432\u0438\u043b\u044c\u043d\u043e\u0439 \u0435\u0433\u043e \u0438\u043d\u0442\u0435\u0440\u043f\u0440\u0435\u0442\u0430\u0446\u0438\u0438.<\/p>\n

          \u041a\u0430\u043a \u043f\u0440\u0430\u0432\u0438\u043b\u044c\u043d\u043e \u043f\u043e\u0434\u0433\u043e\u0442\u043e\u0432\u0438\u0442\u044c\u0441\u044f \u043a \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044e?<\/strong><\/p>\n

            \n
          • \u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u0441\u044f \u0432 \u0441\u043e\u0441\u0442\u043e\u044f\u043d\u0438\u0438 \u0441\u044b\u0442\u043e\u0441\u0442\u0438, \u043d\u0435 \u0440\u0435\u043a\u043e\u043c\u0435\u043d\u0434\u0443\u0435\u0442\u0441\u044f \u0441\u0434\u0430\u0432\u0430\u0442\u044c \u043a\u0440\u043e\u0432\u044c \u043d\u0430 \u0434\u0430\u043d\u043d\u043e\u0435 \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043d\u0430\u0442\u043e\u0449\u0430\u043a.<\/li>\n
          • \u0418\u0441\u043a\u043b\u044e\u0447\u0438\u0442\u044c (\u043f\u043e \u0441\u043e\u0433\u043b\u0430\u0441\u043e\u0432\u0430\u043d\u0438\u044e \u0441 \u0432\u0440\u0430\u0447\u043e\u043c) \u043f\u0440\u0438\u0435\u043c \u0430\u043d\u0442\u0438\u0431\u0430\u043a\u0442\u0435\u0440\u0438\u0430\u043b\u044c\u043d\u044b\u0445 \u0438 \u0445\u0438\u043c\u0438\u043e\u0442\u0435\u0440\u0430\u043f\u0435\u0432\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u0445 \u043f\u0440\u0435\u043f\u0430\u0440\u0430\u0442\u043e\u0432 \u0432 \u0442\u0435\u0447\u0435\u043d\u0438\u0435 14 \u0434\u043d\u0435\u0439 \u0434\u043e \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044f.<\/li>\n
          • \u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u0440\u0435\u043a\u043e\u043c\u0435\u043d\u0434\u0443\u0435\u0442\u0441\u044f \u043f\u0440\u043e\u0432\u043e\u0434\u0438\u0442\u044c \u043d\u0435 \u0440\u0430\u043d\u0435\u0435 \u0447\u0435\u043c \u0447\u0435\u0440\u0435\u0437 2 \u043d\u0435\u0434\u0435\u043b\u0438 \u043f\u043e\u0441\u043b\u0435 \u043f\u0435\u0440\u0435\u043d\u0435\u0441\u0435\u043d\u043d\u044b\u0445 \u0438\u043d\u0444\u0435\u043a\u0446\u0438\u043e\u043d\u043d\u044b\u0445\/\u043e\u0441\u0442\u0440\u044b\u0445 \u0432\u043e\u0441\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0445 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0439.<\/li>\n<\/ul>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[969],"product_tag":[],"class_list":{"0":"post-47904","1":"product","2":"type-product","3":"status-publish","5":"product_cat-teste-de-genetica-umana","7":"first","8":"instock","9":"shipping-taxable","10":"purchasable","11":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/47904","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/comments?post=47904"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=47904"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=47904"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=47904"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=47904"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}