

jagged 1 ("jagg 1") hii paach peshi prushthbhagavaril prathinanpaiki (legands) eka aahe jee sastan pranyanchya notch signalling margatil chaar receptors sanvad sadhate. notch signalling marg haah eka atyant sanrakshit marg aahe joou anek avyav pranalinmadhye peshichya niyatiche nirnay sthapit karnyasathi aanee niyantrit karnyasathi karya karato. ekada jaag-1-notch (receptor-legand) parasparsanvad jhaala qee, proteolytic fatyancha eka pravah suru hoto jyacha parinam khalchya dishene lakshya kelelya janukansathi pratilekhan sakriy honyat hoto. manvi gunasutra 20 varr sthit asalele, "jug 1" januk shariratil anek avyav pranalinmadhye vyakt kele jaate aanee janukatil karya utparivartananchya hanimule autosomal dominant disorder alagil syndrome (aii. ell. jee. ess.) nirman hote. karya laa see. dii. 339 (bhinnatecha samooh 339) mhanoon dekhil niyukt kele gele aahe.
rachana aanee karya.
karya heey pratham legand mhanoon olakhale gele jeey 1995 madhye sastan prani undaramadhye clone kelyavar notch receptors sakriy karnyas saksham hote. teey manvi gunasutra 20 varr cytogenetic sthan 20p12.2 aanee genomic sthan sthan chr 20:10,618,331-10,654,693 varr sthit aahe. aahe prathinanchya sanrachanet eka lahan antakoshiy ghatak, eka transmembrane rachana samavisht aahe, jee cysteine-samruddha pradesh, 16 egf-sarkhya punaravrutti, dsl domain aanee shevati 26 coding exon lambichya 1218 amino acidcha signal peptide asalelya bahya koshikeey pradeshadvare pudhe jaate.
jaag 1' dware encode kelele jaag 1 prathine heey drosophila dandalelya prathinache manvi samaroop aahe. manvi jaag 1 heey notch signalling margatil receptorsasathi paach legandspacky eka aahe jeey cellular bhavitavya nirdharit karnyas madat karate aanee anek vikasatmak tappyanmadhye sakriy asate. jaag 1 prathinancha bahya koshikeey ghatak tyachya sambandhit notch receptorshee sharirikaritya sanvad sadhato. yaa parasparsanvadamule proteolytic fatyanchya eka pravahala suruvat hote jyamule mool payariche antarjivakshetra peshichya kendrakamadhye taskari kele jaate jyamule vividh lakshya januke sakriy hotat.
abhivyakti profile aanee maus abhyas.
inn seatoo sankarikaran aanee sashart januk nockout abhyasanmule vikasat 'jaag 1' chee bhoomika aanee vividh avyav pranalinvar tyache parinam darshavinyat madat jhaali aahe. manavanmadhye, 'jaag 1' chee abhivyakti anek prakarchya uutinmadhye vyapak asate, jyat swadupind, hriday, naal, prostate, fuffuse, mootrapind, thymus, vrushan aanee praudhanmadhye leukocytes yancha samavesh hoto. vikasit hott asalelya garbhamadhye 'jug 1' hii abhivyakti fuffusiy dhamani, mesocardium, durastha cardic pravah marg, pramukh dhamani, metanephros, shakheey kamani, swadupind, portal vhen aanee autosystchya bhovati kendrit asate. samanyatah, "jug 1" abhivyaktiche namune heey algjmadhye prabhavit jhalelya avyav pranalinshi sambandhit asatat, jaree heey lakshat ghene mahatvache aahe qee jyaa serve uutinmadhye jaag 1 vyakt kele jaate tyaa algjmadhye prabhavit hott naheet. agadi alikadech stanacha karkarog aanee adrenocortical carcinoma rugnanmadhye jaag 1 abhivyakti badalaleli aadhalali aahe.
undaranche namune jethe vishisht uutinmadhye jaag 1 januk bund kele jaate (sashart nockout maus models) anek uutinchya vishisht bhaganmadhye jaag 1 chya bhoomikecha abhyas karnyasathi vaparale gele aahet. jaag 1 chey samarupata asalele vilopan heey undaranmadhye garbhjanya ghatak asalyache disun aale aahe aanee vishamjaivata asalele vilopan heey keval maryadit phenotype (dolhyacha samavesh asalele) darshavu shakate, tarr algs phenotypes upasthit jaag 1 aanee notch 2 yaa donhisathi under apure aahet. portal vhen messenkime, endothelium aanee cranial neural crestla lakshya kelelya jagg 1 utparivartanansaha sashart januk nockout maus models serve algs asalelya vyaktinmadhye classic vaishishtye pradarshit karatat, rogachya utpattimadhye yaa uutinchya prakarachi bhoomika adhorekhit karatat.
rog phenotype.
algs haah eka autosomal prabal bahu-pranali vikar aahe joou yakrut, hriday, sangada, dolha, dolha rachana, mootrapind aanee raktavahinya pranali yasah anek shareer pranalinvar parinam karato. yakrut, hriday, raktavahinya kinwa mutrapindachya samasyanmule vaidyakiyadrushtya sarvat mahattvapoorn samasya udbhavtat. 1997 madhye philadelphiyachya baal rugnalay aanee rashtriy aarogya sansthanmadhil sanshodhakanni 'jagg 1' madheel utparivartan heey algsasathi jababdar asalyache pahilyanda shodhun kadhale. vaidyakiyadrushtya yaa vikaras susangat asalelya rugnanmadhye sahasa 'jagg 1' (94 takke) madhye utparivartan hote, tarr lahan 2 takke rugnanmadhye 'notch 2' madhye utparivartan hote. janukatil utparivartan asalelya nimmyahoon adhik vyaktinna teey donhi palkankadun varshane midale nahee aanee tyamule tyanche 'dii novo' utparivartan hote. "jaag 1" utparivartanachya prakaranmadhye prathine kapane (splies site, frameshift aanee murkhapana), missense aanee sampoorn januk hatvane yancha samavesh aahe, jeey anukrame 80 takke, 7 takke aanee 12 takke aahet. serve utparivartananche prakar rugnachya phenotypela karanibhoot tharatat, asey manale jaate qee "jug 1" sathee haploenspufiency hii sambhavya rog yantrana aahe. jaree vyaktinmadhye 'jaag 1' madhye utparivartanache prakar asoo shakatat, taree serve dnyat utparivartananmule eka pratiche karya qamee hote aanee utparivartanacha prakar kinwa sthan aanee rogachi tivrata yanchyat konatahi sambandh nahee. jaree algs asalelya vyaktinchya shariratil anek pranali prabhavit jhalya asalya taree, 'jagg 1' utparivartane asalelya vyaktincha eka upasanch aahe, jeey phelot/pulmonary stenosischya tetrologies upasthit asatat, jeey syndromechi itar vaidyakeey chinhe darshavat naheet. rogachi parivartanshil abhivyakti pahata, mool "jug 1" utparivartanachya palikade itar anuvanshik kinwa paryavaraniy badal asoo shakatat.
agadi alikade, anek prakarchya karkaroganmadhye karkaroganmadhye abhivyaktitil badal samavisht kele gele aahet. visheshtah, jaag 1 chey niyaman heey stanachya karkarogachya jaganyache ekoon qamee praman aanee adrenocortical carcinoma rugnanmadhye gathanchya prasarat vaadh yaa donhinshi sambandhit aahe.

