Abaphandi baye baphatha ngempumelelo ilahleko yokuva yelifa kwiimpuku besebenzisa imolekyuli encinci yechiza ekhokelela kwithemba elitsha unyango ngenxa yobuthulu
Ukulahlekelwa kwindlebe okanye u sithulu kubangelwa lilifa lemfuza kubantu abangaphezu kwama-50 ekhulwini. Sesona siphene sixhaphakileyo ekuzalweni esinokubakho kwiintsana ezingekazalwa. Iimeko zemfuzo zinoxanduva ukuzalwa ukungeva kakuhle kunye negalelo kwi-50% yeemeko zokungeva kwiintsana ezisanda kuzalwa kunye neentsana. Ukungeva okunjalo kuchaphazela amalungu entsapho ekubeni umntu enokufumana ilifa lemo eguqukileyo geni okanye imizila yemfuza okanye imfuza engafunekiyo eyenza le lahleko yenzeke. Ukulahlekelwa kokuva okuzuzw’ ilifa okukhoyo ekuzalweni kukwakhapha nezinye impilo imiba efana nengxaki ngombono kunye nokulinganisela ubuncinane kwi-30 ekhulwini yamatyala. Kwanaxa inzala ingabonakalisi ngxaki yokungeva kakuhle, inokuyizuza njengelifa le gene. Oku kuthetha ukuba umntu ungumthwali. Umthwali wotshintsho lwemfuza onganqwenelekiyo unokuludlulisela kwinzala yexesha elizayo enokuthi emva koko ibe nokungeva kakuhle. Esi sithulu asinyangeki.
Kwiphononongo epapashwe kuyo iseli, Izazinzulu kwiYunivesithi yase-Iowa kunye neZiko leSizwe leZithulu kunye nezinye iZiphazamiso zoNxibelelwano, baye bafumanisa okokuqala ichiza elincinci le-molecule elinokugcina ukuva kwiimpuku ezibandezelekayo kwi-hereditary progressive deafness. Abaphandi bakwazile ukubuyisela ukuva ngokuyinxenye kwizandi ezincinci zezandi kwaye basindise ezimbalwa “kwiiseli zeenwele ezingaphakathi” ngaphakathi kwindlebe. Olu phononongo alukhange lukhanyise kuphela eyona ndlela yemolekyuli egxininisa olu hlobo luthile lwesithulu ngokwemfuza (ebizwa ngokuba yi-DFNA27) kodwa luphakamisa unyango olunokubakho kulo.
Uphononongo lwaqala xa abaphandi bezama ukuhlalutya isiseko sofuzo solu hlobo lokungeva luzuzwe njengelifa kwiminyaka elishumi eyadlulayo. Bajonga ulwazi lwemfuzo lwamalungu osapho (ekubhekiswa kulo njenge-LMG2). Ukungeva kwakugquba kolu sapho okt babephethe imfuza elawula ubuthulu kwaye nayiphi na inzala eyayifuneka kuphela ukuba ifumane ikopi enye yemfuza yemfuza enempazamo kumama okanye kutata ukuze babe nolu hlobo lwesithulu. Kuphando lwabo oluthathe malunga neshumi leminyaka, abaphandi balufumana kwindawo yotshintsho oluye lwabangela ubuthulu “kwingingqi” ebizwa ngokuba yi-DFNA27. Lo mmandla uquka malunga neshumi elinesibini lemizila yemfuza ethi xa itshintshiwe inokukhokelela ekuphulukaneni neendlebe, ngoko ke eyona ndawo yotshintsho yayingekachazwa. Iseti yamva yezifundo incede ukukhomba iimpuku iRestgene (RE1 Silencer Transcription Factor) kwaye abaphandi bafumanise ukuba iimpuku Rest gene ilawulwa yinkqubo engaqhelekanga kwiiseli zendlebe kwaye oku kubaluleke kakhulu kumsebenzi wokuva kwesilwanyana esanyisayo. Abaphandi baye baqala ukuvavanya ingingqi ye-DFNA27 njengoko kwabonwa ukuba ijini yokuPhumla komntu ikule ndawo kuphela. Nje ukuba indawo kunye nomsebenzi we-Restgene uqondwe ngcono, uhlalutyo olongezelelweyo lwenziwa ukuze kubonwe ukuba yintoni enokulungelelanisa le gene kwaye incede ukuphucula ukungeva.
IRestgene ke yasetyenziswa ukuze kudalwe imodeli yokungeva apho imifuniselo inokwenziwa khona. Kwabonwa ukuba iiseli zeenwele ezizivayo zatshatyalaliswa ngaphakathi kweempuku ezingaphakathi endlebeni zibenza bazizithulu. Ukuguqulwa okufanayo kwafunyanwa kusapho lwe-LMG2 ngokunjalo. Xa ukuguqulwa kwaguqulwa, i-REST iprotheyini iyacima kwaye iijene ezininzi zitshintshile zikhokelela ekuvuseleleni iiseli zeenwele ezinzulu kwaye zanceda iigundane ukuba ziphulaphule kangcono. Ke ngoko, isitshixo yi-REST protein efakwe kwi-Rest gene. Le proteni ikholisa ukucinezela imfuza ngendlela ebizwa ngokuba yi "histone deacetylation". Abaphandi basebenzise imolekyuli encinci yechiza enokuthi "isebenze njengokutshintsha" kwaye inokuthintela le nkqubo ye-histone deacetylation kwaye ngaloo ndlela icime iprotein ye-REST. Ukucima i-Rest gene emva koko kwavumela iiseli zeenwele ezintsha ukuba zakhiwe ezithi ekugqibeleni zibuyisele ukuva kwiimpuku.
Olu luphononongo olubalulekileyo nolufanelekileyo ekuhlalutyeni iindlela zangaphakathi ezichaza uhlobo lokungeva oluzuzwa lufuzo. Nangona olu phononongo lwenziwe kwiimpuku, amacebo atyhilwe apha angasetyenziselwa umntu uvavanyo. Sisiqalo esihle sokwenza izifundo ezongezelelweyo apho i-molecule encinci isekelwe iziyobisi inokuboniswa iyasebenza ekunyangeni ubuthulu be-DFNA27. Olu phononongo lunokubanakho ukongezwa kwezinye iintlobo zokulahleka kokuva okuqhubelekayo okubangwa kukuzuza ilifa zendalo. Izikhokelo zofuzo zibonelela ngolwazi oluthe kratya ukufumanisa iindlela ezintsha zokuyila unyango olunokubakho lokungeva kwabantu. Kwakhona, iimolekyuli ezincinci ezingakumbi zinokusetyenziswa kwixesha elizayo ukunyanga ubuthulu obuzuzwe njengelifa.
***
Umthombo (s)
Nakano Y et al 2018. Iziphene kwi-Alternative Splicing-Dependent Regulation ye-REST Ibangela ukungeva. iseli.
https://doi.org/10.1016/j.cell.2018.06.004
***
