{"id":2404,"date":"2020-06-11T09:30:00","date_gmt":"2020-06-11T09:30:00","guid":{"rendered":"https:\/\/dnaera.com\/ro\/?p=2404"},"modified":"2023-04-17T09:22:25","modified_gmt":"2023-04-17T07:22:25","slug":"19-jun-2020-svetovy-den-kosacikovitej-anemie-2","status":"publish","type":"post","link":"https:\/\/dnaera.com\/ro\/blog\/19-jun-2020-svetovy-den-kosacikovitej-anemie-2\/","title":{"rendered":"19. j\u00fan 2020 \u2013 svetov\u00fd de\u0148 kos\u00e1\u010dikovitej an\u00e9mie"},"content":{"rendered":"\n

Pre\u010d\u00edtajte si viac o geneticky podmienenom ochoren\u00ed, ktor\u00e9 postihuje \u010derven\u00e9 krvinky. Z na\u0161ej DNA anal\u00fdzy m\u00f4\u017eete zisti\u0165, \u010di ste pren\u00e1\u0161a\u010dom tohto ochorenia. <\/em><\/p>\n\n\n\n

Stru\u010dn\u00e1 hist\u00f3ria ochorenia a jeho vznik na molekul\u00e1rnej \u00farovni<\/h2>\n\n\n\n

Kos\u00e1\u010dikovit\u00e1 an\u00e9mia je najzn\u00e1mej\u0161ie ochorenie postihuj\u00face \u010derven\u00e9 krvinky (tzv. erytrocyty). Na molekul\u00e1rnej \u00farovni bola sk\u00faman\u00e1 ako v\u00f4bec prv\u00e9 \u013eudsk\u00e9 monog\u00e9nne ochorenie1<\/sup>. Prv\u00fdkr\u00e1t bola op\u00edsan\u00e1 v roku 1910 lek\u00e1rom Jamesom B. Herrickom, ktor\u00fd u svojich pacientov s ur\u010dit\u00fdmi pr\u00edznakmi objavil pr\u00edtomnos\u0165 erytrocytov s abnorm\u00e1lnymi \u010drtami. Nesk\u00f4r, v roku 1949, si americk\u00fd fyzik a biochemik Linus Carl Pauling so svojimi kolegami v\u0161imol, \u017ee pri tomto ochoren\u00ed doch\u00e1dza v na\u0161om tele k tvorbe abnorm\u00e1lneho hemoglob\u00ednu, ktor\u00fd nazvali ako kos\u00e1\u010dikovit\u00fd hemoglob\u00edn (HbS). Profesor Vernon Ingram pouk\u00e1zal na genetick\u00fa podstatu tejto abnormality \u2013 v\u0161imol si, \u017ee v porad\u00ed aminokysel\u00edn2<\/sup> v tomto prote\u00edne doch\u00e1dza v 6. poz\u00edcii k v\u00fdmene kyseliny glut\u00e1movej za aminokyselinu val\u00edn. T\u00e1to zmena je v\u00fdsledkom mut\u00e1cie na 11. chromoz\u00f3me3<\/sup> v poz\u00edcii 11p15.4. Konkr\u00e9tne sa jedn\u00e1 o substit\u00faciu4<\/sup> adenoz\u00ednu za tym\u00edn v g\u00e9ne5<\/sup> HBB, ktor\u00fd k\u00f3duje \u03b2-re\u0165azec hemoglob\u00ednu.<\/p>\n\n\n\n

Hemoglob\u00edn \u2013 v\u00fdznamn\u00fd posol na\u0161ich buniek<\/h2>\n\n\n\n

Hemoglob\u00edn, \u010derven\u00e9 krvn\u00e9 farbivo, tvor\u00ed najd\u00f4le\u017eitej\u0161iu s\u00fa\u010das\u0165 na\u0161ich \u010derven\u00fdch krviniek – pren\u00e1\u0161a kysl\u00edk do buniek v r\u00e1mci cel\u00e9ho organizmu. Zdrav\u00e9 \u010derven\u00e9 krvinky maj\u00fa tvar diskov, ktor\u00fd im zabezpe\u010duje flexibilitu pri transporte aj t\u00fdmi najmen\u0161\u00edmi krvn\u00fdmi cievami. Tento tzv. bikonk\u00e1vny tvar zv\u00e4\u010d\u0161uje plochu povrchu erytrocytov, \u010d\u00edm u\u013eah\u010duje dif\u00faziu kysl\u00edka a oxidu uhli\u010dit\u00e9ho cez ich plazmatick\u00fa membr\u00e1nu.<\/p>\n\n\n\n

Po deoxygen\u00e1cii6<\/sup> je hemoglob\u00edn S (HbS) 50-kr\u00e1t menej rozpustn\u00fd ako hemoglob\u00edn A (HbA, u zdrav\u00fdch jedincov) a preto sa molekuly HbS radia do dlh\u00fdch polym\u00e9rov7<\/sup> , ktor\u00e9 zapr\u00ed\u010di\u0148uj\u00fa kos\u00e1\u010dikovit\u00fd tvar \u010derven\u00fdch krviniek. T\u00e1to abnormalita sp\u00f4sobuje, \u017ee s\u00fa \u201elepkav\u00e9\u201c a rigidn\u00e9, \u010do v kone\u010dnom d\u00f4sledku vedie k vazookl\u00fazii kapil\u00e1r8<\/sup>. Blok\u00e1cia krvn\u00e9ho prietoku m\u00f4\u017ee vies\u0165 k v\u00e1\u017enym n\u00e1sledkom, napr. k po\u0161kodeniu p\u013e\u00facneho tkaniva alebo k vzniku mozgovej pr\u00edhody. Okrem toho m\u00f4\u017ee doch\u00e1dza\u0165 k po\u0161kodeniu \u010fal\u0161\u00edch nenahradite\u013en\u00fdch org\u00e1nov v na\u0161om tele – sleziny, obli\u010diek a pe\u010dene. Po\u0161kodenie sleziny u men\u0161\u00edch det\u00ed sp\u00f4sobuje, \u017ee sa st\u00e1vaj\u00fa n\u00e1chylnej\u0161\u00edmi na bakteri\u00e1lne infekcie.<\/p>\n\n\n\n

\u017divotnos\u0165 zdrav\u00fdch \u010derven\u00fdch krviniek je 90 a\u017e 120 dn\u00ed, potom doch\u00e1dza k ich rozpadu a nahradeniu nov\u00fdmi erytrocytmi. Pri erytrocytoch kos\u00e1\u010dikovit\u00e9ho tvaru bunky \u201epre\u017e\u00edvaj\u00fa\u201c iba 10 a\u017e 20 dn\u00ed. Ak ned\u00f4jde k r\u00fdchlemu nahradeniu buniek m\u00f4\u017ee ma\u0165 tento stav v\u00e1\u017ene d\u00f4sledky na na\u0161e telo a doch\u00e1dza k tzv. stavu an\u00e9mie. An\u00e9mia je stav organizmu, kedy na\u0161e telo nem\u00e1 dostatok erytrocytov a teda aj hemoglob\u00ednu. Ke\u010f\u017ee hemoglob\u00edn je pren\u00e1\u0161a\u010dom molekuly kysl\u00edku, doch\u00e1dza k tomu, \u017ee kysl\u00edk nie je dopravovan\u00fd do ostatn\u00fdch org\u00e1nov v tele \u010do m\u00f4\u017ee vies\u0165 k ich po\u0161kodeniu. Opakovan\u00e1 blok\u00e1cia prietoku krvi v cievach sp\u00f4sobuje, \u017ee sa bunky st\u00e1vaj\u00fa fragiln\u00fdmi a doch\u00e1dza k ich hemol\u00fdze, \u010doho v\u00fdsledkom je chronick\u00e1 an\u00e9mia.<\/p>\n\n\n\n

V\u00fdskyt kos\u00e1\u010dikovitej an\u00e9mie<\/h2>\n\n\n\n

Kos\u00e1\u010dikovit\u00e1 an\u00e9mia patr\u00ed celosvetovo medzi naj\u010dastej\u0161ie \u0161truktur\u00e1lne hemoglobinopatie. Hemoglobinopatie s\u00fa dedi\u010dn\u00e9 ochorenia sp\u00f4soben\u00e9 poruchou tvorby hemoglob\u00ednu. S\u00fa naj\u010dastej\u0161\u00edm monog\u00e9nne podmienen\u00fdm ochoren\u00edm s vysokou prevalenciou najm\u00e4 v oblastiach Stredozemn\u00e9ho mora, Stredn\u00e9ho v\u00fdchodu, z\u00e1padnej Afriky a \u00c1zie. Pod\u013ea \u0161tatist\u00edk prib\u00fada ka\u017ed\u00fd rok 2 – 7,5 % novo-diagnostikovan\u00fdch pr\u00edpadov s t\u00fdmto ochoren\u00edm, v z\u00e1vislosti od geografickej polohy.<\/p>\n\n\n\n

Genetick\u00e1 podstata ochorenia<\/h2>\n\n\n\n

Kos\u00e1\u010dikovit\u00e1 an\u00e9mia je autozom\u00e1lne reces\u00edvne9<\/sup>\u00a0ochorenie, \u010do znamen\u00e1, \u017ee sa prejav\u00ed len v tom pr\u00edpade ak jedinec zded\u00ed jednu k\u00f3piu mutovan\u00e9ho g\u00e9nu10<\/sup>\u00a0HBB od matky a druh\u00fa k\u00f3piu mutovan\u00e9ho g\u00e9nu HBB od otca. Pravdepodobnos\u0165 tak\u00e9hoto scen\u00e1ra je 25 %, a to len v pr\u00edpade ak s\u00fa obaja rodi\u010dia pren\u00e1\u0161a\u010dmi mut\u00e1cie sp\u00f4sobuj\u00facej kos\u00e1\u010dikovit\u00fa an\u00e9miu (4. potomok na obr. 1). Pravdepodobnos\u0165, \u017ee sa rodi\u010dom narod\u00ed die\u0165a, ktor\u00e9 bude tie\u017e pren\u00e1\u0161a\u010dom ochorenia je 50 % (2. a 3. potomok na obr. 1). \u0160anca, \u017ee ich die\u0165a nezded\u00ed ani jednu k\u00f3piu mutovan\u00e9ho g\u00e9nu a\u00a0bude teda zdrav\u00e9 je 25% (1. potomok na obr. 1).<\/p>\n\n\n\n

Paradoxn\u00e9 je, \u017ee v oblastiach s vysok\u00fdm v\u00fdskytom mal\u00e1rie m\u00f4\u017ee by\u0165 prospe\u0161n\u00e9 by\u0165 pren\u00e1\u0161a\u010dom. Zistilo sa toti\u017e, \u017ee jedinci, ktor\u00ed s\u00fa nosite\u013emi jednej k\u00f3pie mutovan\u00e9ho g\u00e9nu HBB, maj\u00fa ur\u010dit\u00fa ochrann\u00fa v\u00fdhodu proti mal\u00e1rii. V d\u00f4sledku tohto je frekvencia pren\u00e1\u0161a\u010dov kos\u00e1\u010dikovitej an\u00e9mie vysok\u00e1 najm\u00e4 v oblastiach postihnut\u00fdch mal\u00e1riou. <\/p>\n\n\n\n

\"\"
Obr. 1.: Vysvetlenie sp\u00f4sobu prenosu jednotliv\u00fdch g\u00e9nov sp\u00f4sobuj\u00facich kos\u00e1\u010dikovit\u00fa an\u00e9miu.<\/figcaption><\/figure><\/div>\n\n\n\n

A\u017e doned\u00e1vna sa toto ochorenie pova\u017eovalo za tzv. detsk\u00e9 ochorenie, preto\u017ee sa detsk\u00ed pacienti s kos\u00e1\u010dikovitou an\u00e9miou nedo\u017e\u00edvali dospelosti. Av\u0161ak dnes, v \u00e9re pokro\u010dilej lek\u00e1rskej starostlivosti sa ka\u017ed\u00fd druh\u00fd pacient do\u017e\u00edva okolo 50. roku \u017eivota.<\/p>\n\n\n\n

Lie\u010dba tohto ochorenia zah\u0155\u0148a krvn\u00e9 transf\u00fazie, sp\u00f4sobuje ve\u013ek\u00e9 bolesti a komplik\u00e1cie, ba dokonca sa vy\u017eaduje transplant\u00e1cia kostnej drene. Transplant\u00e1cia kostnej drene je naozaj \u201ez\u00e1\u017eitkom\u201c, ktor\u00fd si nepraje nikto z n\u00e1s za\u017ei\u0165. Je to cel\u00e9 na v\u00e1s \u2013 len vy viete urobi\u0165 krok k odhaleniu tajomstva svojej DNA. Preto\u017ee v\u0161etko je v n\u00e1s zak\u00f3dovan\u00e9. Sta\u010d\u00ed len hlb\u0161ie nazrie\u0165 do n\u00e1\u0161ho vn\u00fatra.<\/p>\n\n\n\n

V na\u0161om teste sa zameriavame aj na detekciu kos\u00e1\u010dikovitej an\u00e9mie \u2013 zistite, \u010di ste pren\u00e1\u0161a\u010dom tohto ochorenia.<\/p>\n\n\n\n

Vysvetlivky<\/strong><\/p>\n\n\n\n

  1. Monog\u00e9nne dedi\u010dn\u00e9 ochorenie<\/strong> \u2013 vznik\u00e1 ako n\u00e1sledok mut\u00e1cie v jednom g\u00e9ne.<\/li>
  2. Aminokyseliny<\/strong> \u2013 s\u00fa z\u00e1kladn\u00e9 stavebn\u00e9 \u201ekamene\u201c bielkov\u00edn. S\u00fa to organick\u00e9 zl\u00fa\u010deniny.<\/li>
  3. Chromoz\u00f3my<\/strong> \u2013 s\u00fa tmavo zafarben\u00e9 nukleoprote\u00ednov\u00e9 \u010dastice, ktor\u00e9 dok\u00e1\u017eeme pozorova\u0165 po\u010das delenia sa buniek. Ka\u017ed\u00fd chromoz\u00f3m obsahuje line\u00e1rne usporiadan\u00fa skupinu g\u00e9nov.<\/li>
  4. Substit\u00facia<\/strong> \u2013 z\u00e1mena jednej b\u00e1zy v molekule DNA za in\u00fa (v na\u0161om pr\u00edpade adenoz\u00ednu za tym\u00edn).<\/li>
  5. G\u00e9n<\/strong> \u2013 jednotka dedi\u010dnosti (DNA), ktor\u00e1 je lokalizovan\u00e1 na ur\u010ditom mieste na chromoz\u00f3me. Je to \u010das\u0165 DNA, ktor\u00e1 k\u00f3duje jeden polypeptid.<\/li>
  6. Deoxygen\u00e1cia<\/strong> \u2013 dej ozna\u010duj\u00faci nedostatok molekuly kysl\u00edka.<\/li>
  7. Polym\u00e9ry<\/strong> \u2013 zl\u00fa\u010denina skladaj\u00faca sa z mnoh\u00fdch mal\u00fdch podjednotiek<\/li>
  8. Vazookl\u00fazia kapil\u00e1r<\/strong> – upchatie prietoku krvi v cievach.<\/li>
  9. Autozom\u00e1lne ochorenie<\/strong> \u2013 je ochorenie, ktor\u00e9 postihuje nepohlavn\u00e9 chromoz\u00f3my. \u013dudsk\u00fd organizmus obsahuje 22 p\u00e1rov autozom\u00e1lnych chromoz\u00f3mov a 1 p\u00e1r gonozom\u00e1lnych (pohlavn\u00fdch) chromoz\u00f3mov. Pohlavn\u00e9 chromoz\u00f3my s\u00fa X a Y (XX = \u017eena, XY = mu\u017e).<\/li>
  10. Mut\u00e1cia<\/strong> \u2013 trval\u00e1 dedi\u010dn\u00e1 zmena v sekvencii DNA ur\u010dit\u00e9ho organizmu. Term\u00edn sa pou\u017e\u00edva ako pre ozna\u010denie bodov\u00fdch mut\u00e1ci\u00ed zahr\u0148uj\u00facich zmenu jednotliv\u00fdch g\u00e9nov, tak aj pre ozna\u010denie zmien na \u00farovni chromoz\u00f3mov<\/li><\/ol>\n\n\n\n

    <\/p>\n\n\n\n

    Zdroje<\/strong><\/p>\n\n\n\n

    1. Zuniga C., P., Martinez G., C, Gondalez R., L.M., Rendon C., D., Rojas R., N., Barriga C., F., Wietstruck P., M.A. (2018). Sickle Cell Disease: A Diagnosis to Keep in Mind. Rev Chil Pediatr. 89(4): 525-529.<\/li>
    2. Benenson, I., Porter, S. (2018). Sickle Cell Disease: Bone, Joint, Muscle, and Motor Complications. Orthop. Nurs. 37(4): 221-227.<\/li>
    3. Swensen, J.J., Agarwal, A.M., Esquilin, J.M., Swierczek, S., Perumbeti, A., Hussey, D., Lee, M., Joiner, C.H., Pont-Kingdon, G., Lyon, E., Prchal, J.T. (2010) Sickle cell disease resulting from uniparental disomy in a child who inherited sickle cell trait. Blood .116(15): 2822\u20132825.<\/li>
    4. Luzzatto, L. (2012). Sickle cell anaemia and malaria. Mediterranean journal of hematology and infectious diseases, 4(1).<\/li>
    5. https:\/\/www.genome.gov\/Genetic-Disorders\/Sickle-Cell-Disease<\/li>
    6. https:\/\/rarediseases.info.nih.gov\/diseases\/8614\/disease<\/li>
    7. https:\/\/www.healthline.com\/health\/sickle-cell-anemia#types<\/li>
    8. https:\/\/www.healthline.com\/health\/anemia<\/li>
    9. https:\/\/www.alphamedical.sk\/casopis-invitro\/hemolyticke-anemie<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

      Pre\u010d\u00edtajte si viac o geneticky podmienenom ochoren\u00ed, ktor\u00e9 postihuje \u010derven\u00e9 krvinky. Z na\u0161ej DNA anal\u00fdzy m\u00f4\u017eete zisti\u0165, \u010di ste pren\u00e1\u0161a\u010dom tohto ochorenia. Stru\u010dn\u00e1 hist\u00f3ria ochorenia a jeho vznik na molekul\u00e1rnej \u00farovni Kos\u00e1\u010dikovit\u00e1 an\u00e9mia je najzn\u00e1mej\u0161ie ochorenie postihuj\u00face \u010derven\u00e9 krvinky (tzv. erytrocyty). Na molekul\u00e1rnej \u00farovni bola sk\u00faman\u00e1 ako v\u00f4bec prv\u00e9 \u013eudsk\u00e9 monog\u00e9nne ochorenie1. Prv\u00fdkr\u00e1t bola op\u00edsan\u00e1 v roku […]<\/p>\n","protected":false},"author":1,"featured_media":2405,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"content-type":"","inline_featured_image":false,"footnotes":""},"categories":[1],"tags":[58,59,60],"place-taxonomy":[],"class_list":["post-2404","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized-sk","tag-dna-analyza","tag-dna-test","tag-genetika"],"acf":[],"views":2893,"_links":{"self":[{"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/posts\/2404","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/comments?post=2404"}],"version-history":[{"count":3,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/posts\/2404\/revisions"}],"predecessor-version":[{"id":1352808,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/posts\/2404\/revisions\/1352808"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/media\/2405"}],"wp:attachment":[{"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/media?parent=2404"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/categories?post=2404"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/tags?post=2404"},{"taxonomy":"place-taxonomy","embeddable":true,"href":"https:\/\/dnaera.com\/ro\/wp-json\/wp\/v2\/place-taxonomy?post=2404"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}