გენეტიკა (ტომპსონი და ტომპსონი)

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genetika da genomikamedicinaSi

genetika medicinaSi me-20 saukunis dasawyisSi Se -moiWra, rodesac garodma da sxvebma pirvelebma SeniSnes, rom mendelis memkvidreobis kanonebiT SeiZleboda aexsnaT ojaxebSi zogierTi avad-myofobis ganmeorebis SemTxvevebi. momdevno 100 wlis ganmavlobaSi samedicino genetika mcire qvespecialobidan, romelic mxolod ramdenime memkvidrul darRvevas swavlobda, sayovelTaod aRiarebul samedicino disciplinad Camoyalibda, romlis koncefciebi da meTodebi mravali gav-rcelebuli Tu iSviaTi daavadebis diagnoscire-bis da marTvis mniSvnelovani komponentebia. miT ufro iTqmis es dRes, 21-e saukunis dasawyisSi, adamianis genomis proeqtis saerTaSoriso gran-diozuli dasrulebis Semdeg, romelic adamianis genomis srul gaSifvras isaxavda miznad. genomi SeiZleba ganvsazRvroT rogorc saxeobis gene-tikuri informacia Sejamebuli saxiT (sufiqsi ome berZnulidan warmodgeba da yvelas anu sruls niSnavs). axla Cven ukve SegviZlia gamo-vikvlioT adamianis ara mxolod calkeuli geni, aramed misi genomi rogorc erTiani, mTliani obieqti. samedicino genetika gaxda ufro farTo dargis genomuri medicinis nawili, romlis mizania adamianis genomis vrcelmasStabiani ana-lizis (maT Soris, genis eqspresiaze kontrolis, adamianis genebis cvalebadobis da genTaSoris Tu genebsa da garemos Soris urTierTqmedebis) praqtikaSi gamoyenebis gzebis moZieba samedicino momsaxurebis srulyofis mizniT.

samedicino genetika ar aris orientirebuli mxolod da mxolod avadmyofze, aramed mTlia-nad mis ojaxzec. ojaxis istoriis Sesaxeb amom-wuravi informaciis Segroveba (ojaxis anamnezi) aris pirveli mniSvnelovani safexuri nebismieri daavadebis analizisas, damoukideblad imisa, gene-tikuria Tu ara is. rogorc Caildsi (Childs, 1993) aRniSnavda: Tuki ver SeZleb moipovo avadmyofis ojaxis kargi anamnezi, es ukve cudi medicinaa... ojaxis istoria xSirad gadamwyvetia diagnozis dasmisas. masze dayrdnobiT SesaZlebelia gamov-lindes avadmyofobis memkvidruli buneba, gani-sazRvros misi memkvidreobis tipi da eqspresiis cvalebadoba. ojaxuri komponentis arsebobis

SemTxvevaSi aucilebelia Sefasdes daavadebis riskis xarisxi avadmyofis ojaxis wevrebisaTvis da mieces maT saTanado rekomendaciebi daavade-bis prevenciasTan da mkurnalobasTan dakavSire-biT.

sul bolo ramdenime weliwadSi adamianis genomis proeqtma xelmisawvdomi gaxada infor-macia adamianis dnm-is sruli Tanamimdevrobis Sesaxeb, romlis codna adamianis TiToeuli genis identifikaciis saSualebas iZleva. dResdReo-biT ukve SesaZlebelia ganisazRros sxvadasxva populaciaSi genebis cvalebadobis speqtri da is farglebi, romelSic vrceldeba genebis cvale-badobis zegavlena janmrTelobis SenarCunebaze Tu daavadebis mimdinareobaze. adamianis geno-mis proeqtis ganxorcieleba SesaZlebeli gaxda Tanamedrove biologiis sxvadasxva dargis war-momadgenelTa saerTo ZalisxmeviT da mWidro urTierTTanamSromlobiT. aRniSnuli proeqtis dasruleba revoluciuri miRwevaa da misi da-nergva samedicino praqtikaSi saSualebas miscems klinicistebs ukeT gaerkvnen mravali daavadebis natif meqanizmSi, SeimuSaon daavadebis mimarT saTanado prevenciuli zomebi da mkurnalobis swori strategia.

saorganizacio principebis mixedviT, genetika swrafad ikavebs centralur poziciebs samedicino praqtikaSi. qvemoT mogvyavs genetikisa da geno-mikis medicinaSi gamoyenebis vrceli CamonaT-validan mxolod ramdenime magaliTi:

bavSvi, romelsac aqvs mravlobiTi Tandayo-lili mankebi da rutinuli qromosomuli ana-lizis normaluri suraTi, gadis maRalmgrZno-biare genomur testirebas submikroskopuli deleciebis an dublikaciebis gamosavlenad.

axalgazrda qals mkerdis simsivnis ojaxuri anamneziT utareben saganmanaTleblo saubars, interpretacias ukeTeben testis Sedegebs. amave dros mas aqvs mkerdis simsivnis memkvidruli formebis specialisti-konsultantis Tanadgo-ma.

38 wlis orsuli qalisgan aRebul qorionis xaos nimuSs meani agzavnis citogenetikur la-boratoriaSi raodenobriv-struqturul dar-Rvevebze nayofis qromosomebis Sesamowmeb-lad.

Sesavali

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tompsoni & tompsoni genetika medicinaSi2

hematologi erTmaneTTan ajerebs Rrma vene-bis Trombozis mqone axalgazrda qalis oja-xis da samedicino istoriebs antikoagulan-turi Terapiis dawyebis sargeblianobis da riskis Sesafaseblad.

simsivnis nimuSSi genuri eqspresiis analizi gamoiyeneba prognozisTvis da Terapiis kursis SesarCevad.

onkologi pacients utarebs testirebas geneti-kuri cvlilebebis gamosavlenad qimio-Tera-piul agentze dadebiTi reagirebis an saziano reaqciis prognozebis mizniT.

sasamarTlo-samedicino eqsperti 2001 wlis 11 seqtembers msoflio savaWro centrze ganxor-cielebuli aqtis Semdeg darCenili sxeulis nawilebis saidentifikaciod atarebs msxver-plis nivTebidan da cocxlad darCenili naTe-savebidan gamoyofili dnm-is nimuSebis analizs da sargeblobs genetikuri polimorfizmis monacemTa baziT.

simsivnis dros aRiniSneba arasaTanado mimar-Tulebis sapasuxo reaqcia onkogenur signalze, rac somaturi mutaciiT reaqtivirdeba. am aRmoCenas mivyavarT aRniSnuli mimarTulebis specifikuri da mZlavri inhibitoris aRmoCe-namde, rac simsivnis warmatebuli mkurnalo-bis sawindaria.

genetikuri principebis da meTodebis gamoye-neba medicinaSi ar Semoifargleba mxolod romelime specialobiT an qvespecialobiT, ara-med me di cinis mraval dargSi inergeba. yvela Te rapev tma da maTma yvela kolegam, sxvadasxva samedicino dargis warmomadgenlebma, unda icod-nen adamianis genetikis fundamenturi principebi; mxolod maSin SeZleben isini genetikis miRweve-bis gamoyenebas praqtikul saqmianobaSi, srulfa-sovani daxmarebis aRmoCenas avadmyofis da misi ojaxis wevrebisaTvis. es principebia: genebis alternatiuli formebis (alelebis) arseboba populaciaSi; msgavsi fenotipebis formireba sxvadasxva lokusSi warmoSobili mutaciebisa da cvalebadobis Sedegad; daavadebaTa ganviTare-baSi genTa urTierTmoqmedebisa da genze garemos gavlenis mniSvnelobis gansazRvra; somatur muta-ciaTa roli simsivnis ganviTarebaSi da dabere-baSi; prenataluri diagnostikis SesaZleblobebi; presimptomuri testireba da populaciis skrin-ingi; genuri Terapiis SesaZleblobebisa da sa medicino praqtikaSi maTi danergvis perspeq-tivebis gansazRvra. mniSvnelovania am koncefcie-bis gavlena mTlianad samedicino praqtikaze da momavalSi mosalodnelia maTi mniSvnelobis kidev ufro gazrda.

genetikuri darRvevebis klasifikacia

klinikur praqtikaSi genetikis mTavari daniS-nulebaa gamoavlinos da gamokveTos genetikuri

mravalferovnebisa da mutaciebis roli mraval-ricxovan darRvevaTa etiologiaSi. faqtobri-vad, nebismieri daavadeba genebisa da garemos kombinirebuli moqmedebis Sedegia, sadac gene-tikuri komponentis roli umetesi, an piriqiT minimaluria. im darRvevebs Soris, romlebic mTlianad an nawilobriv genetikuri faqtorebiT gamoiwveva, ganasxvaveben sam ZiriTadi tipis dar-Rvevebs: qromosomuls, monogenurs da multifaq-toruls.

qromosomuli darRvevebis SemTxvevebSi de-feqti gamowveulia ara erTi romelime genis dazianebiT, aramed qromosomaSi an qromosomul segmentSi arsebuli genebis deficitiT an siWar-biT. magaliTad, 21-e qromosomis erTi zedmeti aslis arsebobisas saxezea specifikuri daavadeba daunis sindromi, miuxedavad imisa, rom qromo-somaSi arc erTi geni ar aris defeqturi. qromo-somuli daavadebebi sakmaod xSiria, daaxloebiT 7 SemTxveva 1000 cocxalSobilze, xolo orsulobis pirveli trimestrSi spontanuri abortebis na xe-vari swored qromosomul daavadebebze modis. es darRvevebi ganxiluli iqneba me-6 TavSi.

monogenur darRvevebs individualuri mutan-turi genebi iwvevs. mutacia SeiZleba gvxvdebodes qromosomuli wyvilidan mxolod erT (homolo-giuri qromosomis normaluri alelis mewyvile) an orive qromosomaSi. erTeul SemTxvevebSi mutacia gvxvdeba ara birTvul genomSi, aramed mitoqondriul genebSic. nebismier SemTxvevaSi, amis mizezia seriozuli xasiaTis Secdoma geneti-kur informaciaSi, romelsac atarebs erTeuli geni. monogenur darRvevebs, magaliTad, kistur fibrozs, namglisebrujre-dovan anemias da mar-fanis sindroms, Cveulebriv, kargad gamokveTili specifikuri genealogiuri niSnebi aqvT, aseTi defeqtebi arcTu xSiria, Tumca zogjer SesaZloa 1 : 500 an 1 : 1000 sixSiresac miaRwios. iSviaTobis miuxedavad, monogenur darRvevebze modis daa-vadebebisa da sikvdilianobis SemTxvevaTa mniS-vnelovani wili. mTlianad populaciis masStabiT, mTeli sicocxlis periodis gaTvaliswinebiT, monogenuri darRvevebi vlindeba mosaxleobis 2%-Si. populaciur gamokvlevaSi, romelic 1 mil-ion cocxladSobil Cvilze Catarda, aseTi Sede-gi dafiqsirda: bavSvTa populaciaSi seriozuli monogenuri darRvevebis ricxvma 0,36%, xolo hospitalizebul bavSvebSi 6-8% Seadgina. aRniS-nul darRvevebs me-7 TavSi ganvixilavT.

multifaqtoruli memkvidreoba gvxvdeba daavadebaTa umravlesobaSi da yvela maTgani atarebs genetikur faqtors, razec metyvelebs Semdegi faqtebi: daavadebul individTa naTe-savebSi daavadebis gameorebis riski sakmari-sad maRalia; avadmyofobis gamovlenis maRali sixSire identur tyupebSi. ojaxebSi vlindeba zogierTi daavadebis memkvidruli buneba, Tumca memkvidreobis suraTi aSkarad ar Seesabameba erTi genis defeqtiT gamowveul suraTs. multi-faqtoruli darRvevebi moicaven prenataluri ganviTarebis anomaliebs, rac Tandayolil simaxinjeebs (rogoricaa hirSprungis daavade-

Tavi 1 Sesavali 3

ba, gapobili tuCi da sasa, gulis Tandayolili mankebi) da zrdasrul asakSi gamovlenil mraval darRvevas (alchaimeris sindromi, diabeti, hip-ertenzia) iwvevs. es dakavSirebulia genetikuri informaciis ara erTeul cvlilebasTan, aramed erTi, ori an meti sxvadasxva genis (maT, erTad aRebuls, SeuZlia gamoiwvios seriozuli defeq-ti an mianiWos individs daavadebis mimarT winas-warganwyoba) da garemo faqtorebis erTdroul moqmedebasTan. multifaqtoruli daavadebebis populaciuri sixSire 5%-dan (bavSvebSi) 60%-mde (mTlianad populaciaSi) meryeobs. zemoT CamoTv-lili darRvevebi me-8 TavSi gansaxilveli Temis sagania.

momavlis perspeqtiva

unda movelodeT, rom specialistebisa da aspi-rantebis dRevandeli Taobis momavali 50-wliani profesiuli moRvaweoba udides aRmoCenebs mou-tans mecnierebas da mniSvnelovnad waswevs win genetikisa da genomikis codnis da meTodebis gamoyenebas medicinaSi. Tu warsuls gadavavlebT Tvals, Znelia gaixseno esoden didi cvlilebebiT aRsavse periodi, rogoric iyo gasuli 50 weli, romlis ganmavlobaSic dargma gaiara ganviTare-bis gza dnm-is, rogorc memkvidrulobis ganmsaz-

Rvreli agentis, pirvelaRmoCenidan dnm-isa da qromosomebis molekuluri struqturis da ada-mianis genomis srul gaSifvramde. mxolod gasu-li aTwleulis aRmoCenebiT Tu ganvsjiT, cxadi gaxdeba, rom Cven im revoluciuri gzis mxolod dasawyisSi varT, romelic gulisxmobs genetikisa da genomis miR wevebis integracias sazogadoebriv jandacvasTan da praqtikul medicinasTan. adami-anis da samedicino genetikis terminologiisa da koncefciebis gacnoba, janmrTelobis dacvaze da avadmyofobis mdgomareobaze genetikis da geno-mikis gavlenis perspeqtivebis saTanado Sefaseba aris is principuli sakiTxebi, romelTa codna da am codnis mudmivi srulyofa janmrTelobis dacvis sferoSi dasaqmebul yovel profesionals moeTxoveba.

ZiriTadi literatura

Guttmacher AE, Collins FS: Genomic medicine-a primer. N Engl J Med 347:1512-1520, 2002.

Peltonen L, McKusick VA: Genomics and medicine. Dissecting human disease in the postgenomic era. Science 291:1224-1229, 2001.

Willard HF, Angrist M, Ginsburg GS: Genomic medicine: genetic variation and its impact on the future of health care. Philos Trans R Soc Lond B Biol Sci 360:1543-1550, 2005.

medicinaSi genetikis mniSvnelobis gansazRvri-saTvis saWiroa gvesmodes memkvidruli masalis buneba, vicodeT, Tu rogor aris is Calagebuli adamianis genomSi da rogor gadaecema ujre-didan ujreds gayofisas, an Taobidan Taobas gamravlebis procesSi. adamianis genomi didi odenobiT Seicavs dezoqsiribonukleinis mJavas (dnm-s), romelSic genetikuri informaciaa kodi-rebuli. igi gansazRvravs embriogenezis, ganvi-Tarebis, zrdis, metabolizmisa da reproduqciis arsebiTad yvela im aspeqts, romelic ayalibebs adamians rogorc funqcionirebad organizms. sxeulis yvela birTviani ujredi atarebs ada-mianis genomis sakuTar asls. uaxlesi monaceme-biT, adamianis genomi 25000-mde struqturul gens, genetikuri informaciis erTeuls Seicavs. genebi ganlagebulia dnm-Si, romelic TiToeuli ujre-dis birTvSi arsebuli Cxiriseburi struqture-bis qromosomebis SemadgenlobaSi Sedis. didia da yovlismomcveli genebisa da genetikis gav-lena janmrTelobis da avadmyofobis mdgomar-eobaze da am gavlenis wyaro aris genomis dnm-Si kodirebuli informacia. Cveni codna adamianis genomis bunebis da genebis raobis, agreTve ada-mianis genomis Sedgenilobis Sesaxeb ukanaskneli aTwleulebis manZilze gasaocari tempiT gaizarda da kulminacias 2003 wels miaRwia, rodesac faq-tobrivad dasrulda adamianis mTliani genomis dnm-is Tanamimdevrobis gansazRvra.

yoveli saxeobisaTvis damaxasiaTebelia qro-mosomaTa garkveuli kompleqti (kariotipi) gan-sazRvruli ricxviT da morfologiiT. genebi qromosomebSi zustad gansazRvruli Tanamimdev-robiTaa ganlagebuli. TiToeul gens sakuTari adgili anu lokusi aqvs. qromosomebSi genebis adgilmdebareobas gamosaxaven qromosomul ru-kaze, romelic gansxvavebulia TiToeuli saxeo-bisTvis da saxeobaSi TiToeuli individisa-Tvis.

adamianis qromosomebs, maT struqturasa da memkvidreobas Seiswavlis citogenetika. ada-mianis Tanamedrove citogenetikis istoria 1956 wlidan iwyeba, rodesac pirvelad daadgines, rom

adamianis normaluri qromosomuli kompleqti 46 qromosomisagan Sedgeba. mas Semdeg bevri ram iqna garkveuli qromosomebis Sesaxeb: dadge ni lia qromosomebis normaluri struqtura da mole-kuluri Sedgeniloba, maTSi arsebuli genebis lokalizaciis adgili da am genTa cvlilebebiT ganpirobebuli mravalricxovani darRvevebi.

qromosomuli analizi klinikuri medicinis mniSvnelovani diagnostikuri meTodi gaxda. ufro srulad am meTods momdevno TavebSi gan-vixilavT, aq ki mxolod maTi mokle gansazRvre-biT SemovifarglebiT:

klinikuri diagnostika. mravali daavadeba, maT Soris farTod gavrcelebuli daunis sindromi, dakavSirebulia qromosomebis ricxvis an stru q - turis mikroskopulad xilul cvlilebebTan da diagnostikisa da genetikuri konsultaciisaTvis qromosomul analizs saWiroebs (ix. Tavi 5 da 6);

genetikuri kartireba da identifikacia. samedi-cino genetikis mTavari mizani dResdReobiT aris qromosomebSi specifikuri genebis ganlagebis rukis Sedgena da maTi rolis gansazRvra jan-mrTelobis uzrunvelyofasa da avadmyofobis inducirebaSi. es sakiTxi detalurad me-10 TavSi ganixileba.

simsivnis citogenetika. somatur ujredebSi war-moSobili genomuri da qromosomuli cvlile-bebi dakavSirebulia sxvadasxva tipis simsivnuri zrdis iniciaciasTan da ganviTarebasTan (ix. Tavi 16).

prenataluri diagnostika. qromosomuli da genomuri analizi prenatalur diagnostikaSi gamoyenebuli ZiriTadi meTodia (ix. Tavi 15).

qromosomuli analizis monacemebis interpre-taciis unari, meTodologiis da qromosomuli kvlevis SesaZleblobaTa zRvaris codna aucile-belia Terapevti-eqimebisaTvis da im medperso-nalisTvis, romlebic Tandayolili defeqtebis, gonebrivi CamorCenilobis, seqsualuri ganviTa-rebis anomaliebis mqone da sxvadasxva tipis sim-sivniT daavadebul pacientebTan muSaoben.

adamianis genomi da memkvidrulobis qromosomuli safuZvlebi

2T a v i


sur. 2-1 birTvul da mitoqon-driul dnm-Si kodirebuli adamia-nis genomi. (Modified from Brown TA: Genomes, 2nd ed. New York, Wiley-Liss, 2002.)

...CAGGTCTTAGCCATTCGGAATCGTACGCTAGCAATTCTTATGGAAACTGTGAAGGCTTATAAT...

adamianis genomis Tanamimdevrobebi

somaturi ujredi

birTvuli qomosomebi

mitoqondriuliqromosomebi

adamianis genomi da qromosomebi

adamianis sxeulis yvela ujreds, gametebis wina-morbedi (germinaciuli) ujredebis garda, soma-tur ujredebs uwodeben (berZn. soma sxeuli). adamianis somaturi ujredis birTvSi arsebuli 46 qromosoma warmodgenilia 23 wyviliT (sur 2-1); aqedan 22 wyvili rogorc mamakacebSi, ise qaleb-Si struqturulad identuria da maT autosomebs uwodeben. autosomebs zomis mixedviT udidesi-dan umciresisken daalageben. qromosomebis erTi darCenili wyvili 23-e, sasqeso qromosomebia, romlebic qalebSi warmodgeni-lia X qromo-somebiT, mamakacebSi ki X da Y qromosomebiT. TiToeuli qromosoma atarebs genebis sxvadasxva kompleqts, romlebic xazobrivad aris dawyobili dnm-Si. yoveli qromosomuli wyvili Sedgeba ori morfologiurad msgavsi qromosomisagan, rom-lebsac homologiuri qromosomebi anu homolo-gebi ewodeba. homologiuri wyvilis wevri qro-mosomebi erTmaneTTan dasawyvilebel genetikur informacias Seicavs, anu identuri genebi erT-nairi Tanamimdevrobi Taa ganlagebuli, Tumca nebismier specifikur lokusSi isini SeiZleba Sei-

cavdes erTdaimave genis identur an mcired gan-sxvavebul formebs. aseT genebs alelebs uwode-ben. yoveli qromosomuli wyvilis erTi wevri memkvidreobiT aris miRebuli mamisagan, xolo meore dedisagan. normaSi, autosomuri wyvilis wevrebi mikroskopulad ar gansxvavdebian erT-maneTisagan. qalebSi sasqeso qromosomebi ori X qromosoma, erTmaneTis identuria; mamakacebis sasqeso qromosomebidan ki erTi aris X, romelic qalis X qromosomis identuria da mamakaci mem-kvidreobiT iRebs de disagan, Tavad ki qaliSvils gadascems; meore Y qromosoma memkvidreobiT miRebulia mamisagan da gadaecema vaJiSvils. me-6 TavSi ganvixilavT zogierT gamonakliss am mar-tivi da TiTqmis universaluri wesidan, romlis mixedviT, mdedrobiTi sqesis individebi Seicaven XX, xolo mamrobiTi sqesis individebi XY qro-mosomebs.

adamianis genomSi birTvul genomTan erTad arsebobs adamianis genomis mcire, magram mniS-vnelovani nawili, romelic mitoqondriaSi, cito-plazmaSi arsebobs (ix. sur. 2-1). mitoqondriuli qromosoma, rogorc amas amave TavSi qvemoT gan-vixilavT, atarebs mTel rig uCveulo Tvisebebs, rac mas adamianis genomis danarCeni nawilidan gamoarCevs.

Tavi 2 adamianis genomi da memkvidrulobis qromosomuli safuZvlebi 7

sur. 2-2 dnm-is 4 azotovani fuZe da nukleotidis zogadi struqtura. TiToeuli fuZe qimiuri bmiT ukav-Sirdeba dezoqsiribozas (azotis sa-SualebiT, naCvenebia lurjad) da fosfatur jgufs, ris Sedegadac war-moiqmneba Sesabamisi nukleotidi.

purinebi pirimidinebi

adenini Timini

fosfati

dezoqsiriboza

guanini citozini

dnm-is struqtura: mokle mimoxilva

vidre adamianis genomis organizaciis da misi qromosomebis detalur ganxilvas SevudgebodeT, saWirod migvaCnia mimovixiloT dnm-is, rogorc genomis Semadgeneli molekulis buneba. dezoqsi-ribonukleinis mJava (dnm) polimeruli nuklei-nis mJavis makromolekulaa, romelic sam kompo-nents Seicavs: xuTnaxSirbadian Saqars, dezoqsi-ribozas; azotSemcvel fuZes da fosfatur jgufs (sur. 2-2). fuZeebi ori tipisaa, purinebi da piri-midinebi. dnm-is molekulaSi aris purinis ori adeninisa (A) da guaninis (G), da pirimidinis ori Timinisa (T) da citozinis (C) azotovani fuZe. nukleotidebi, romlebic fuZis, fosfatisa da Saqris komponentebisagan Sedgeba, ganicdis polimerizacias grZel polinukleotidur jaWve-bad: mezobeli dezoqsiribozas molekulebi 5'-3' fosfodieTeruli bmebiT ukavSirdebian erT-maneTs (sur. 2-3). es polinukleotiduri jaWvebi (orspiraliani formiT) adamianis genomSi aso-biT milion nukleotids Seicavs da maTi sigrZe did farglebSi variirebs 50 milioni fuZeTa wyvilidan (yvelaze mcire zomis, 21-e qromoso-misTvis) 250 milion fuZeTa wyvilamde (yvelaze didi zomis 1-eli qromosomisTvis).

dnm-is Sinagani struqtura Seicavs qimiur informacias, romelic saSualebas iZleva zus-tad gadaeces genetikuri informacia ujredidan Svileul ujreds da Taobidan momdevno Taobas. amave dros, dnm-is pirveladi struqtura gansaz-Rravs cilebSi aminmJavebis Tanamimdevrobas. dnm-is `daxvewili~ maxasiaTeblebi mis Tvisebebs gansazRvravs. 1953 wels jeims uotsonma da fren-sis krikma gaSifres dnm-is molekulis nativuri struqtura (sur. 2-4). is ormagi marjvniv mxvevi spiralia, romlis or urTierTsawinaaRmdegod mimarTul polinukleotidur jaWvs erTmaneTis pirispir amagrebs fuZeTa wyvilebs Soris war-moqmnili wyalbaduri bmebi: erTi jaWvis A ukav-Sirdeba meore jaWvis T-s, xolo G - C-s (ix. sur. 2-4). adamianis genomSi kodirebuli genetikuri

informacia C-, A-, G-sa da T-ebis Tanamimdevrobe-bSia ganTavsebuli rogorc birTvuli, ise mito-qondriuli qromosomis gaswvriv dnm-is or Zaf-Si (ix. sur. 2-1). dnm-is ori Zafis komplementaru-li bunebidan gamomdinare, erTi nukleotiduri jaWvis Tanamimdevrobis codna saSualebas gvaZ-levs gamovicnoT meore jaWvis mimdevroba. dnm-is molekulis orZafiani struqtura ganapirobebs misi zusti replikaciis SesaZleblobas, rac ori jaWvis dacalkevebis da sawyisi matriculi Zafis nukleotiduri Tanamimdevrobebis Sesabamisi axali komplementuri Zafis sinTezis gziT miiR-weva (sur. 2-5). amis msgavsad, azotovani fuZeebis komplementaroba, saWiroebis SemTxvevaSi, erTi jaWvis dazianebuli nawilis Seucdomlad, zustad da efeqtianad aRdgenis saSualebas iZleva.

adamianis qromosomebis organizacia

adamianis genomSi genebis Sedgeniloba da eqspre-sia, birTvis 46 qromosomaSi da mitoqondriul qromosomaSi warmodgenili dnm-iT ganisazRvre-ba. rogorc ukve vnaxeT zemoT, adamianis qromo-soma erTi grZeli orspiraliani dnm-sagan Sed-geba, anu yoveli birTvuli qromosoma grZeli, xazovani, orZafiani dnm-is molekulaa da birTvis genomi Seeicavs Sesabamisad 46 dnm-is molekulas, sul 6 miliard nukleotidze mets (ix. sur. 2-1).

amasTanave, qromosoma ar aris mxolod SiSve-li dnm-is ormagi spirali. genomi yovel ujred-Si qromatinis saxiT arsebobs, romelSic genomu-ri dnm ramdenime klasis qromosomul cilasTan aris asocirebuli. zogierTi cila qromosomis struqturis SeqmnaSi monawileobs, sxvebi indi-vidualuri genebis eqspresias areguli rebs. interfazis periodSi qromatini mTel birTv -Sia ganawilebuli da mikroskopis qveS Sedare-biT homogenur masad moCans. ujredis gayofis dros birTvis masala kondensirdeba, qromoso-mebis saxes iRebs da mikroskopSi xiluli xdeba. amrigad, qromosoma, rogorc calkeuli xilvadi struqtura, mxolod ujredis gayofis dros arse-

fuZe


sur. 2-3 dnm-is polinukleotiduri jaWvis nawili. naCvenebia 3'-5' fosfodieTeruli bmebi, romlebic mezo-bel nukleotidebs akavSirebs erTmaneTTan.

5' daboloeba

3' daboloeba

sur. 2-4 dnm-is struqtura. marcxniv, dnm-is ori komplemen-taruli Zafis organzomilebiani struqtura, sadac naCvenebia AT da GC fuZeTa wyvilebi. yurad-Reba miaqcieT, rom Zafebi mi-marTulia antiparalelurad. mar jvniv, uotsonis da krikis mier SemoTavazebuli dnm-is or-magi spiralis modeli.Hhori-zontaluri xidakebi aRniSnavs dawyvilebul fuZeebs. miiCneven, rom spirali aris marjvnivmxve-vi, radgan jaWvi, romelic mie-marTeba marcxena qveda mxridan marjvena zeda mxares, gadakveTs sapirispiro jaWvs. (Based on Wat-son JD, Crick FHC: Molecular structure of nucleic acids-a structure for deoxyri-bose nucleic acid. Nature 171:737-738, 1953.).

wyalbaduribmebi

bobs, xolo gayofebs Soris periodSi, anu inter-fazaSi, misi danaxva SeuZlebelia

qromosomis dnm-is molekula qmnis kom-pleqss fuZovan qromosomul cilebTan, romleb-sac histonebs uwodeben da heterogenur arahis-tonur mJave cilebTan, romlebic gacilebiT nak-lebadaa Seswavlili, magram, savaraudod, maT gansakuTrebuli roli unda hqondeT qromoso-maTa normaluri qcevisa da genebis eqspresiisaT-vis saTanado garemos Seqmnis saqmeSi.

arsebobs histonebis xuTi didi jgufi, romel-sac gansakuTrebiT mniSvnelovani roli akis-riaT qromatinuli Zafebis swor CalagebaSi. oTxi histonuri H2A, H2B, H3, H4 wyvili qmnis oqtamers, romelzec dnm-is segmenti isea daxveu-li, rogorc Zafi gorgalze (sur. 2-6). TiToeul histonur oqtamerze (e.w. gulze) daaxloebiT 140 fuZeTa wyvilis sigrZis dnm daexveva. is TiTqmis or bruns akeTebs gulis garSemo. sigrZis mcire intervalis Semdeg, romelic dnm-is 20-dan 60-mde fuZeTa wyvilis sigrZis speiserul (dauxvevel) segments moicavs, formirdeba momdevno dnm-his-tonuri kompleqsis guli da a.S., rac qromatins Zafze asxmuli mZivis Sesaxedaobas aniWebs. dnm-isa da gulis (core) histonebis kompleqss nukleo-soma ewodeba, romelic qromatinis struqturuli erTeulia. mexuTe histoni H1, dnm-s ukavSirde-ba TiToeuli nukleosomis kideze, internukleo-somur speiserul ubanSi. nukleosomis birTvTan asocirebuli dnm-is moculoba, speiserul uban-Tan erTad, daaxloebiT 200 f.w.-is tolia.

histonebis msxvili jgufebis garda arsebo-bs kidev specializebuli histonebi, romlebsac SeuZliaT Caenacvlon H3 da H2A histonebs da genomur dnm-s am adgilebSi specifikuri Tvise-bebi mianiWon. H3 da H4 histonebs aseve SeuZliaT kodirebuli cilebis qimiuri gardaqmnebis Sede-gad ganicadon garkveuli modifikacia. am e.w. posttransliaciur modifikacias (ix. me-3 Tavi)

pirveli fuZe

meore fuZe

mesame fuZe


sur. 2-5 dnm-is ormagi spiralis replikacia, romlis Sedegad warmoiqmneba dnm-is ori identuri Svileuli molekula, TiToeuli maTgani Sedgeba erTi Zveli (nacrisferi) da erTi axalsinTezirebuli Zafisagan (lurji).

sur. 2-6 qromatinis struqturis ierarqiuli doneebi adamianis qromosomaSi.

histonis oqtameri

ormagi spirali nukleosomuri fibrila(Zafze acmuli mZivis marcvlebi)

solenoidi interfazuli birTvi

interfazuli qromosomis nawili

yoveli maryuJi Seicavs dnm-is ~100000 f.w.-s

2 nm ~10 nm ~30 nm

dnm-is ~140 f.w.

ujreduli ciklis ganmavlobaSi, rogorc amas amave TavSi vnaxavT qvemoT, qromosomebi gadian kondensaciisa da dekondensaciis stadiebs. Tumca maSinac ki, rodesac isini maqsimalurad dekon-densirebul mdgomareobaSi imyofebian, anu ujre-duli ciklis interfazis stadiaze qromosomis qromatinis kondensaciis xarisxi mainc bevrad aRemateba dnm-is ormagi spiralis kondensaciis maCvenebels nativur, histonebisagan Tavisufal mdgomareobaSi. SemdgomSi grZeli nukleoso-muri Zafebi kidev ganicdian kompaqtizacias da yalibdeba meoradi spiraluri qromatinuli struqtura, romelic eleqtronul mikroskopSi msxvili, 30 nm diametris (nukleosomur Zafebze TiTqmis samjer msxvil) Zafebad moCans (ix. sur. me-2-6). es cilindruli solenoidis Zafi (saxel-wodeba warmosdgeba berZnuli sityvisagan solenoei-des milis formis) qromatinis organizaciis ZiriTadi erTeulia. Tavis mxriv, solenoidebi maryuJebad anu domenebad Caewyoba da miema-greba arahistonuri cilebis RerZs, anu mat riqss daaxloebiT 100 000 fuZeTa wyvilis (rac 100 kilobasi wyvilis eqvivalentia anu 100 kb, radgan 1 kb=1000 fuZeTa wyvils) intervalebiT. gamoT-qmulia mosazreba, rom maryuJi, faqtobrivad, aris dnm-is replikaciis an genis transkrifciis funqciuri erTeuli, an orivesi erTad. amasTa-nave, TiToeuli maryuJis mimagrebis wertile-bi fiqsirebulia qromosomuli dnm-is gaswvriv. amrigad, genis eqspresiis kontrolis erT-erTi done SesaZloa damokidebuli iyos imaze, Tu rogoraa dnm da genebi Cawyobili qromosomeb-Si, da rogoria am Cawyobis procesSi maTi kav-Siri qromatinis cilebTan.

qromosomaSi Calagebuli dnm-is uzarmazari moculobis saTanado aRqma xdeba maSin, rodesac qromosomas specialurad daamuSaveben qromati-nuli cilebis mocilebis mizniT da akvirdebian

SeuZlia Secvalos im nukleosomaTa Tvisebebi, romlis SemadgenlobaSic Sedian es histonebi. msxvil da specializebul histonis tipebs da maT modifikaciebs xSirad histonur kods uwodeben, romelic SesaZloa variirebdes sxvadasxva ujre-dis tipebSi da gansazRvravdes dnm-is Calagebis xasiaTs da kidev, ramdenad misaRebia es regula-tori molekulebisTvis, romlebic genis eqspre-sias Tu genomis sxva funqciebs gansazRvravs.

5' 3' 5' 3'

3' 5'

3' 5'


ufro didi kompleqsurobiT xasiaTdeba, vidre es windawin iyo navaraudevi. aRmoCnda, rom, faqtob-rivad, 3 miliardi fuZeTa wyvilidan 1,5%-ze nak-lebi kodirebs cilebs da mxolod 5% Seicavs maregulirebel elementebs, romlebic gavlenas axdenen genebis eqspresiis suraTze ganviTarebis dros an sxvadasxva qsovilebSi. mTliani xazo-vani genomis mxolod naxevari Sedgeba e.w. erT calad warmodgenili unikaluri dnm-sagan, anu dnm-sagan romlis nukleotiduri Tanamimdevroba mxolod erT (an ramdenime) caladaa warmodgeni-li haploidur genomSi. genomis danarCeni nawili Sedgeba ganmeorebiTi dnm-is ramdenime klasisa-gan da moicavs dnm-s, romlis nukleotiduri Tana-mimdevroba zustad, an umniSvnelod saxecvlili, mravaljer meordeba genomSi dawyebuli asi-dan milioniT damTavrebuli. radgan umetesoba genebisa (magram ara yvela) genomSi arsebuli im 25 000 genidan, dnm-is erT calad warmodgenili genebia, maSasadame, qromosomuli struqturis dacvas ganmeorebadi dnm-is Tanamimdevrobebi uzrunvelyofs da sxadasxva individebs Soris variaciebis umniSvnelovan wyaros warmoadgens. am variaciebidan zogierTs SeuZlia ganapirobos paTologiuri SemTxvevebi genomSi, romlebsac Cven me-6 TavSi vnaxavT.

erT calad warmodgenili dnm-is Tanamimdevrobebi

miuxedavad imisa, rom dnm-is erT calad warmod-genili Tanamimdevrobebi genomuri dnm-is, sul mcire, naxevars Seadgens, maT funqciebis umrav-lesoba saidumloebiT moculi rCeba, vinaidan, rogorc zemoT ukve aRvniSneT, Tanamimdevrobe-bi, romlebic namdvilad kodirebs cilebs (mako-direbeli genebi) Seadgens erT calad warmod-genili dnm-is mTliani moculobis Zalze mcire nawils. aseTi dnm-is umetesoba mokle fragmen-tebadaa danawevrebuli (ramdenime kb an naklebi) da interspersuladaa CarTuli sxvadasxva saxis ganmeorebadi dnm-is ojaxebis wevrebs Soris. genebSi dnm-is erT calad warmodgenili Tanamim-devrobebis organizacias ufro Rrmad me-3 TavSi ganvixilavT.

ganmeorebadi dnm-is Tanamimdevrobebi

ganmeorebadi dnm-is ramdenime kategoriaa aR-moCenili. maTi urTierTgansxvavebisaTvis mosa-xerxebelia ganisazRvros, Tu rogor arian gan-meorebadi Tanamimdevrobebi (ganmeorebado-bebi) ganawilebuli: erT an ramdenime adgilas lokalizebul klasterebad, Tu dispersulad mTel genomSi, sadac isini monacvleoben inter-spersulad CarTul qromosomis gaswvriv arse-bul erT calad warmodgenil Tanamimdevrobeb-Tan. ganmeorebad TanamimdevrobaTa klasterebi genomis 10-15%-s Seadgens da Sedgeba tandemurad, Tavi-kudis principiT dakavSirebuli mokle ganmeorebadobebisagan. aseTi tandemuri ganmeo-rebadobebis sxvadasxva tipebs aqvT koleqtiuri

cilis RerZs (sur. 2-7). rodesac amgvari wesiT damuSavebuli qromosomidan gamoaTavisufleben dnm-s, masze kargad Cans grZeli maryuJebi; moCans aseve RerZis naSTi, romelic tipuri metafazuri qromosomis konturebs imeorebs.

mitoqondriuli qromosoma

rogorc zemoT ukve aRvniSneT, adamianis genomSi Semavali genebis mcire, magram ujredisTvis mniS-vnelovani nawili citoplazmaSi, kerZod, mito-qondriebSic gvxvdeba (ix. sur. 2-1). am genebis memkvidruli gadacema mxolod da mxolod dedis xaziT xdeba (ix. me-7 Tavi). adamianis ujredebSi asobiT da aTasobiT mitoqondriaa da yoveli maTgani mcire zomis rgoluri molekulis asle-bis garkveul raodenobas, mitoqondriul qromo-somas, Seicavs. mitoqondriuli dnm-is molekulis sigrZe mxolod 16 kb-ia (yvelaze mcire birTvu-li qromosomis sigrZis 0,03% naklebi!) da mxo-lod 37 makodirebel gens Seicavs, risTvisac iye-nebs trip letur kods, magram aq is umniSvnelod gansxvavdeba birTvuli tripleturi kodisagan. am genTa produqtebi mitoqondriebSi funqcio-nireben, magram mitoqondriuli cilebis udide-si nawili mainc birTvuli genebis produqtia. naCvenebia ramdenime mitoqondriuli genis muta-ciiT gamowveuli, dedisagan memkvidreobiT miRe-buli daavadeba da zogierTi sporaduli forma (SemTxveva 28) (ix. me-7 da me-12 Tavi).

adamianis genomis organizacia

genomis ubnebi, romlebsac organizaciis msgav-si niSnebi, replikacia da eqspresia axasia TebT, ganawilebuli arian ara SemTxveviT, aramed daj-gufebuli arian klasterebad. genomis aseTi fun-qciuri organizacia ZiriTadad mis struqturul organizacias Seesabameba, rogorc es qromosomu-li analizis laboratoriuli meTodebiT vlin-deba (am sakiTxs am TavSi zogadad mimovixilavT, detalurad ki me-5 TavSi SemogTavazebT). aseTi funqciuri organizaciis mniSvneloba imaSi mdgo-mareobs, rom qromosoma ar aris mxolod da mxo-lod genebis da dnm-is TanamimdevrobaTa SemTxve-viTi dajgufeba. zogierTi qromosomuli ubani da TviT mTliani qromosomac ki, mdidaria genebiT (genebiT mdidari ubnebi), maSin, roca sxvebi mci-re raodenobiT genebs Seicavs (genebiT Rari-bi ubnebi) (ix. sur. 2-8). dnm-is Tanamimdev ro baTa garkveuli tipebi adamianis qromosomis sxva-dasxva fizikur Tavisebure bebs Seesabameba. geno-mis struqturis darRvevaTa klinikuri Sedegebi asaxavs Secvlili genebisa da Tanamimdevrobe-bis specifikur bunebas. amrigad, mosalodnelia, rom darRvevebi genebiT mdidar qromosomebSi an qromosomul ubnebSi klinikurad gacilebiT ufro mZime iqneba, vidre genomis analogiuri defeqtebi genebiT Rarib regionebSi.

~adamianis genomis proeqtis ganxorciele-bis Sedegad SeZenilma codnam cxadi gaxada is faqti, rom adamianis genomuri dnm gacilebiT


sur. 2-7 adamianis metafazuri qromosomis eleqtronuli mikrografia cilebis mocilebis Semdeg. naCvenebia narCeni qromosomis ConCxi da dnm-is maryuJebi. dnm-is calkeuli Zafebi ukeT Cans dnm-is jaWvis boloze. Bar = 2 m. (From Paulson JR, Laemmli UK: The structure of histone-depleted metaphase chromosomes. Cell 12:817-828, 1977. Reprinted by permission of the authors and Cell Press.).


sur. 2-8 adamianis 24 qromosomis zoma da genebis Semcveloba. A. adamianis calkeuli qromosomis zoma, gamosaxulia milionobiT fuZeTa wyvilSi (1 mln fuZeTa wyvili = 1 Mb). qromosomebi dawyobilia zomis mixedviT marcxnidan marjvniv. B. adamianis calkeul qromosomaSi identificirebuli genebis raodenoba. qromosomebi daw-yobilia genebis raodenobrivi Semcvelobis mixedviT marcxnidan marjvniv. (Based on data from www.ensembl.org, v36.).

saxelwodeba satelituri dnm. es saxelwodeba ukavSirdeba sawyisi tandemuri ganmeorebadobe-bis ojaxis Tvisebas, simkvrivis gradientSi cen-trifugirebisas gamoeyos genomis mTel danar-Cen nawils, rogorc dnm-is sateliti fraqciebi.

ganmeorebad TanamimdevrobaTa dnm-is oja-xebi gansxvavdeba genomSi maTi lokalizaciis adgilis, tandemuri mwkrivebis saerTo sigrZis da calkeuli ganmeorebadi elementebis sigrZis mixedviT. zogadad satelituri ganmeorebadobebi SeiZleba ramdenime milion fuZeTa wyvils moi-cavdes da adamianis individualuri qromosomis dnm-is moculobis ramdenime procents Seadgen-des. bevri maTgani mniSvnelovani molekuluri iaraRia, romelmac revoluciuri siaxle Semoita-na klinikuri citogenetikuri analizis meTodeb-Si da gaadvila gamokvlevebis Catareba (ix. me-5 Tavi). adamianSi zogierTi ganmeorebadi Tanamim-devroba Zalze moklea da xuTi nukleotidisa-gan Sedgeba. grZeli mwkrivebi aris gamovlenili 1-eli, me-9 da me-16 qromosomebis grZeli mxris proqsimaluri ubnis heteroqromatul ubnebSi da Y qromosomis TiTqmis mTlian grZel mxarSi (ix. me-5 Tavi). sxva ganmeorebad TanamimdevrobaTa

dnm-is ojaxebi SedarebiT grZelia, magaliTad, dnm-is -satelituri ojaxi daaxloebiT 171 f.w. Semcveli erTeulebis tandemuri mwkrivebisagan Sedgeba da is gamovlenilia adamianis yvela qro-mosomis centromerul ubanSi. am ganmeorebadi ubnebis ojaxebi garkveul rols unda asruleb-des centromeris funqcionirebaSi, kerZod mitoz-Si da meiozSi qromosomaTa swor segregaciaSi, rogorc amas Semdeg TavSi ganvixilavT.

tandemurad ganmeorebadi dnm-is garda, geno-mi Seicavs ganmeorebadi dnm-is kidev erT klass, romlis Tanamimdevrobebs ara aqvT garkveuli lokalizaciis adgili da dispersulad arian gabneuli mTel genomSi. es gansazRvreba dnm-is bevr mcire ojaxs miesadageba, magram maTgan gansakuTrebiT unda gamoiyos ori ojaxi, rom-lebTanac asocirdeba genetikuri daavadebebis ganviTareba. yvelaze kargad Seswavlili disper-siuli ganmeorebadi elementebi e.w. Alu ojaxSi erTiandeba. am ojaxis wevrebi sigrZiT 300 fuZe-Ta wyvils Seadgens da erTmaneTis msgavsi, Tum-ca araidenturia. mTlianobaSi adamianis genomi milionamde Alu ojaxis wevrs moicavs, rac Sead-gens adamianis dnm-is, sul mcire, 10%-s. genomis

qro

moso

mis

zo

ma (M

b)ge

nebi

s r

aod

eno

ba


zogierT regionSi isini procentulad dnm-is umetes nawils Seadgens. dispersuli ganmeore-badi dnm-is meore didi ojaxia grZeli, inter-spersuli birTvuli elementebis (LINE, xandaxan SemoklebiT L1-s uwodeben) ojaxi. maTi sigrZe 6 kb-mde aRwevs, genomSi 850 000-mde asliTaa war-modgenili da genomis daaxloebiT 20% Seadgens. isini araTanabradaa ganawilebuli genomSi: L1-iT mdidari ubnebi mcirericxovani elementebis Sem-cvel ubnebTan monacvleoben.

ganmeorebadi dnm da daavadebebi. ganmeoreba-dobaTa ojaxebi, romlebic dispersiulad arian gabneuli genomSi, Zalze mniSvnelovania samedi-cino TvalsazrisiT. rogorc Alu, ise LINE Tana-mimdevrobebi gavlenas axdens mutaciis induqci-aze, rac iwvevs retrotranspoziciis proceseb-Tan dakavSirebul memkvidrul daavadebebs. sul mcire, ramdenime asli LINE da Alu ojaxebisa jer kidev aqtiuri rCeba transpoziciis Tval-sazrisiT. isini TviTon qmnian aslebs, romelTac SeuZliaT genomis nebismier adgilas integri-reba da inserciis adgilas garkveuli genebis inaqtivacia. zogjer inaqtivirebuli geni Zalze mniSvnelovania samedicino TvalsazrisiT. ret-rotranspoziciis SemTxvevaTa sixSire, romelic adamianSi genetikur daavadebas iwvevs, amJamad zustad ar aris dadgenili, magram gansazRvrulia misi wili mu taciaTa saerTo raodenobaSi 1:500. garda amisa, araswori rekombinacia LINE da Alu-s sxvadasxva asls Soris SeiZleba gaxdes geneti-kuri daavadebis gamomwvevi mutaciis mizezi (ix. Tavi 9).

ganmeorebadi dnm-is kidev erTi mniSvnelo-vani damatebiTi klasi dublicirebul Tanamim-devrobebs Seicavs. isini xSirad Tanamimdevro-baTa uCveulod maRali konservaciis xarisxiT gamoirCeva da genomis sxvadasxva ubanSi loka-lizdeba. dublikaciebs, romlebic qromosomis mniSvnelovan segmentebs moicavs, segmentur dub-likaciebs uwodeben. isini asobiT aTas fuZeTa wyvilzea gadaWimuli da mTeli genomis daax-loebiT 5%-s Seadgens. Tu dublicirebuli ubnebi Seicavs genebs, aseT TanamimdevrobaTa momcveli dublicirebuli regionebis gadaadgilebam SesaZ-loa gamoiwvios aslebs Soris ubnis (da genebis) delecia da gamoiwvios daavadebaTa ganviTareba (ix. Tavi 6). amasTanave, genomSi segmentebis erT-maneTis mimarT adgilmdebareobis Secvla gansaz-Rvravs individTaSorisi gansxvavebebis farTo speqtrs da ganpirobebulia dnm-is zemoaRniSnul TanamimdevrobaTa aslebis mravalricxovnebiT. am sakiTxs ufro detalurad Mme-9 TavSi ganvixi-lavT.

ujredis gayofa

ujredebis gayofis ori tipi arsebobs: mitozi da meiozi. mitozi somaturi ujredebisaTvis damaxasiaTebeli gayofaa, romelic safuZvlad

udevs sxeulis zrdas, diferencirebas da qso-vilebis regeneracias. mitozuri gayofis Sedegad erTi mSobliuri ujredidan miiReba ori Svile-uli ujredi da TiToeuli maTgani Seicavs saw-yisi ujredis identur qromosomebsa da genebs. somaturma ujredebma SesaZloa aTobiT da aso-biT warmatebuli mitozuri gayofa ganicados. mitozisagan gansxvavebiT, meiozi mxolod germi-naciul ujredebSi xdeba, ris Sedegadac warmoiq-mneba sasqeso ujredebi (gametebi). TiToeul game-tas 23 qromosoma aqvs: erTi TiToeuli wyvili autosomidan da erTic sasqeso qromosoma, X an Y. amrigad, somaturi ujredebi Seicavs qromo-somebis diploidur (berZn. diploos gaormagebu-li) anu 2n kompleqts (e. i. 46 qromosomas), xolo gametebi haploidur (berZn. haploos erTeuli), anu n kompleqts (e.i. 23 qromosomas). qromoso-mebis ricxvisa da struqturis cvlilebebs xSi-rad klinikurad mniSvnelovani gamovlineba aqvs, rasac swored somaturi an germinaciuli ujre-debis dayofis dros daSvebuli Secdomebi gana-pirobebs.

ujreduli cikli

adamianis ganviTareba ganayofierebuli kvercx-ujredidan (zigotidan) iwyeba. diploiduri ujredis ramdenime aTeuli da aseuli mitozuri dayofis Sedegad adamianis organizmis yvela (daaxloebiT 100 trilioni) ujredi warmoiqmne-ba. miuxedavad imisa, rom mitozs gadamwyveti mniS-vneloba aqvs organizmis zrdisa da diferencire-bis procesSi, ujredis sasicocxlo ciklSi misi wili SedarebiT mcirea. ujredis ciklis periods or srul mitozur gayofas Soris ewodeba inter-faza, mdgomareoba, romelSic ujredi sasicoc-xlo ciklis umetes nawils atarebs.

mitozis dasrulebisTanave ujredi Sedis faza-Si, romelsac G

1-iT aRniSnaven. am fazaSi dnm-is

sinTezi ar mimdinareobs (suraTi 2-9). zogierTi ujredi xangrZlivad yovndeba G

1 fazaSi dReebis,

Tveebis an wlebis ganmavlobaSi, zogierTi ki mxolod ramdenime saaTs. faqtobrivad, zogierTi tipis ujredebi rogoricaa neironebi da sisxlis wiTeli ujredebi, maRaldiferencirebuli arian da sruliad ar iyofian; isini mudmivad imyofe-bian G

1 stadiisGaradayofad G0 fazaSi (G nuli).

sxva ujredebi, rogoricaa hepatocitebi, Sedian G0 fazaSi, magram organos dazianebis SemTxvvaSi SeuZliaT daubrundnen G

1 stadias da xelaxla

CaerTon ujredul ciklSi.

ujreduli ciklis makontrolebeli moleku-luri meqanizmebi bolomde garkveuli ar aris. cnobilia, rom ujredis cikli imarTeba rigi sakontrolo ubnidan, romlebic mitozis calkeu-li fazis xangrZlivobas gansazRvravs. sakontro-lo ubnebi Tvalyurs adevneben da akontroleben rogorc dnm-is sinTezis sizustes, ise specialuri mikromilakebis qselis awyobas da dakavSire-bas qromosomebTan. mikromilakebi uzrunvel-yofs qromosomaTa moZraobas. ujredis genomis


sur. 2-9 teqstSi aRwerili tipuri mitozuri ujreduli cikli. naCvenebia telomerebi, centromera da Svileuli qromatidebi.

telomera

centromera

telomera

Svileuli qromatidebi

dazianebis SemTxvevaSi, mitozis makontrole-beli ubnebi aCereben ujredis ciklis mimdi-nareobas manamde, sanam darRveva ar gaswordeba. Tu dazianeba seriozulia da misi gamosworeba SeuZlebelia, maSin mitozis makontrolebeli ubnebi ujredis kvdomis brZanebas iZlevian, rac ujredis programirebuli kvdomiT mTavrdeba (am process apoptozi ewodeba).

G1 fazas mosdevs S faza, anu dnm-is sinTezis

faza. am fazaSi yoveli qromosoma, romelic G1

fazaSi dnm-is erTi molekulisagan Sedgeboda (mis struqturas me-3 TavSi ganvixilavT), ga nic-dis replikacias (ormagdeba) da ori Svileuli qromatidisagan iqmneba qromosoma (ix. sur. 2-9). TiToeuli qromatida dnm-is sawyisi xazovani molekulis identur asls Seicavs. yoveli qro-mosomis (an qromatidis) boloebs telomerebi ewodeba. telomeris ubanSi dnm-s aqvs nukleotide-bis specifikuri Tanamimdevroba, romelic ujre-dis gayofis dros qromosomis mTlianobis Senar-Cunebas uzrunvelyofs. ori Svileuli qromatida fizikurad erTmaneTTan centromeris saSualebiT aris dakavSirebuli. es ukanaskneli warmoadgens dnm-is ubans, romelTanac mravali specifikuri cilaa dakavSirebuli da warmoqmnis kinetoqors. es rTuli struqtura mitozuri TiTistaris mik-romilakebTan TiToeuli qromosomis mimagrebas emsaxureba da mitozis dros qromosomebis moZ-raobas warmarTavs. S fazis ganmavlobaSi dnm-is sinTezi asinqronulad mimdinareobs rogorc qromosomul nakrebSi, ise calkeul qromosoma-Si. ufro metic, TiToeuli qromosomis gaswvriv asobiT da aTasobiTa saitia, sadac dnm-is sinTezi iwyeba. maT dnm-is replikaciis dawyebis saitebs uwodeben. individualuri qromosomebis segmen-tebs maTTvis damaxasiaTebeli replikaciis dro aqvs, romlis xangrZlivoba S fazaSi 6-8 saaTiT ganisazRvreba.

S fazis bolosaTvis ujredSi arsebuli dnm-is raodenoba gaormagebulia da ujredi Sedis momdevno, SedarebiT xanmokle G2 fazaSi. ujre-

dis mTliani ciklis ganmavlobaSi ribonuklei-nis mJavebisa da cilebis sinTezi mimdinareobs, ujredi zomaSi TandaTan matulobs da momdevno mitozis win misi masa gaormagebulia. G2 fazis damTavrebisTanave iwyeba mitozi, romlis dro-sac individualuri qromosomebi kondensirebas iwyeben da SesaZlebeli xdeba mikroskopSi maTi danaxva wvrili, grZeli Zafebis saxiT. mitozis procesi detalurad Semdeg qveTavSia ganxiluli.

ujredis ciklis G1,

S da G2 fazebi erTad Sead-

gens interfazas. adamianis tipuri dayofadi ujre-debis ciklSi am samive fazis jamuri xangrZlivoba 16-24 saaTia, maSin rodesac mitozis xangrZlivoba mxolod 1-2 saaTia (ix. sur. 2-9). aRsaniSnavia, rom sxvadasxva tipis ujredSi sasicocxlo ciklis xangrZlivoba did farglebSi meryeobs. im ujre-debSi, romlebsac swrafi gamravleba axasiaTebs (kanis dermisa da nawlavis lorwovani epiTeli-umis ujredebSi), misi xangrZlivoba ramdenime saaTia, xolo sxva tipis ujredebSi ramdenime Tve.

mitozi

mitozi somaturi ujredebis arapirdapiri gayo-faa, romlis drosac TiToeuli Svileuli ujre-di mSobeli ujredisagan genetikuri informaciis srul kompleqts miiRebs, es Sedegi ki yoveli qromosomis erTi qromatidis TiToeul Svile-ul ujredSi ganawilebis gziT miiRweva (sur. 2-10). yoveli qromosomis TiTo aslis gadasvlas calkeul Svileul ujredSi qromosomebis segre-gacia ewodeba. ujredebis normaluri zrdisTvis am process didi mniSvneloba eniWeba, rasac adas-turebs is faqti, rom mravali simsivnuri ujre-disaTvis damaxasiaTebelia genetikuri balansis darRveva, rac mitozis procesSi qromosomebis Svileul ujredebSi qromosomebis araswori gadanawilebis Sedegia.

mitozi uwyveti procesia, magram masSi ganirCe-va xuTi stadia: profaza, prometafaza, metafaza, anafaza da telofaza.

profaza. es mitozis pirveli fazaa. am dros TiToeuli qromosoma, romelic ori qroma-tidisagan Sedgeba, TandaTanobiT kondensirdeba da mkafiod Cans. birTvaki gauCinardeba da iwyeba mitozuri TiTistaris Camoyalibeba. mikromila-kis war-momqmneli wyvili struqtura, romlebsac centrosomebs uwodeben, qmnis centrebs, saidanac sxivurad gamodis mikromilakebi. centrosomebi ujredis polusebisaken TandaTanobiT moZraobs da iq ganlagdeba.

prometafaza. ujredi maSin Sedis prometafazaSi, rodesac birTvis membrana irRveva, rac qromo-somebs ujredis citoplazmaSi Tavisuflad gan-lagebis saSualebas aZlevs. qromosomebi mito-zuri TiTistaris mikromilakebs kinetoqorebis saSualebiT ukavSirdebian da iwyeben moZraobas TiTistaris polusebisaken. am process kongresia ewodeba. qromosomebi kondensacias mTeli pro-

G1(10-12 hr)

G2(2-4 hr)

S(6-8 hr)

M


sur. 2-10 mitozi. sqematur suraTze gamosaxulia mxolod ori qromosomuli wyvili. de-talebi ix. teqstSi.

ujredebi G2 fazaSi

ujredebi G1 fazaSi

S faza

citokinezi

telofaza

anafaza

prometafaza

profaza

centrosomebi

interfaza

mitozis dasawyisi

metafaza

mikromilakebi

metafazuri stadiis ganmavlobaSi ganagrZoben.

metafaza. metafazaSi qromosomebi maqsimalur kondensacias aRweven. isini ujredis ekvatorul sibrtyeSi ganlagdebian. es procesi balansirdeba TiTistaras ori polusidan gamomavali mikromi-lakebidan wamosuli ZafebiT, romlebic Tanab-rad moqmedebs TiToeuli qromosomis kineto-qorze. adamianis dayofad ujredSi qromosomebis analizisaTvis yvelaze mosaxerxebelia mitozis metafazis an prometafazis stadiebi (ganxilva ix. me-5 TavSi).

anafaza. anafazis stadia iwyeba maSinve, rogorc ki qromosomebi gaiTiSeba centromeris ubanSi. TiToeuli qromosomis qromatidebi ukve damou-kidebel Svileul qromosomebad gadaiqceva, romlebic ujredis sapirispiro polusebisaken miemarTeba (ix. sur. 2-10).

telofaza. telofazaSi maqsimalurad kompaqti-zebuli qromosomebi dekondensirebas iwyeben. TiToeuli Svileuli birTvis garSemo xelaxla formirdeba birTvuli membrana da TiToeuli birTvi TandaTan ibrunebs im pirvandel saxes, romelic interfazaSi hqonda.

ujredis gayofa mTavrdeba citoplazmis ga yo-fiT da am process citokinezs uwodeben. igi iwyeba TiTistaris polusebTan qromosomebis miaxloe-bisas. sabolood miiReba ori Svileuli ujredi; TiToeulis birTvi mSobeli ujredis srul gene-tikur informacias Seicavs.

mitozSi Sesuli ujredi mniSvnelovnad gan-sxvavdeba im ujredisagan, romelic mitozis dam-Tavrebis Semdeg warmoiqmneba. G2 fazaSi mSobli-uri ujredis yoveli qromosoma wyvili qroma-tidisagan Sedgeba, xolo Svileuli ujredis qro-mosoma genetikuri masalis mxolod erT asls Seicavs. am aslis gaormageba ar moxdeba manam,

sanam Svileuli ujredi, Tavis mxriv, Semdgomi ciklis S fazas ar miaRwevs (ix. sur. 2-9). amrigad, mitozis erTiani procesi ujredis sworad war-marTuli gayofis SemTxvevaSi genomis mowesrige-bul gaormagebasa da ganawilebas uzrunvelyofs.

adamianis kariotipi

adamianis ujredis kondensirebuli qromosome-bis analizi yvelaze mosaxerxebelia mitozis metafazaSi an prometafazaSi. am dros qromosome-bi mikroskopSi xiluli xdeba da moCans, rogorc qromosomuli ganbneva. TiToeuli maTgani Sed-geba centromeriT erTmaneTTan dakavSirebuli Svileuli qromatidebisagan.

qromosomebi ZiriTadad erTmaneTisagan sig-rZiT da centromeris adgilmdebareobiT gan-sxvavdeba. centromera aris Svileuli qromati-debis SemakavSirebeli ubani da moCans rogorc pirveladi Wimi, is qromosomas or mokle da grZel mxrebad yofs da citogenetikur marke-rad gamoiyeneba. qromosomis mokle mxari p (petit) asoTi aRiniSneba, xolo grZeli q asoTi. Tavdapirvelad adamianis citogenetikuri anali-zisaTvis xelmisawvdomi SeRebvis meTodebi 24-ve tipis qromosomis (22 autosomis, X- da Y-qromo-somebis) individualuri identifikaciis saSua-lebas ar iZleoda. qromosomebis klasifikacias safuZvlad daudes qromosomebis zoma da maTi centromerebis adgilmdebareoba, ris mixedviTac, qromosomebi dayves 7 jgufad. TiToeuli jgufi aRniSnes laTinuri anbanis asoebiT A-dan G-mde. amJamad aseT dayofas iSviaTad mimarTaven, Tumca jer kidev gvxvdeba literaturaSi. sayovelTaod gamoyenebuli Tanamedrove meTodebi individu-aluri qromosomebis identifikaciis saSualebas iZleva.

dekondensirebuli qromatini


sur. 2-11 qromosomuli ganbneva, miRebuli limfoci-turi kulturidan; qromosomebi SeRebilia gimza-ben-direbis (G-bendirebis) meTodiT. suraTze qromosome-bis qveviT moCans sxva interfazuli ujredis muqad SeRebili birTvi difuzuri qromosomuli masaliT. (Courtesy of Stuart Schwartz, University Hospitals of Cleveland, Ohio.)

me-2-11 suraTze naCvenebia prometafazuri ujredi, romlis qromosomebi SeRebilia gimzis (G-bendirebis) meTodiT. aRniSnuli meTodi klini-kur citogenetikur laboratoriebSi yvelaze farTod gamoyenebuli meTodia. qromosomebs jer trifsiniT amuSaveben, raTa daSalon maTTan asocirebuli cilebi, Semdeg ki gimzis saRebaviT faraven. TiToeuli qromosomuli wyvili damaxa-siaTebeli Ria da muq zolebad (G-bendebad) iRe-beba, romlebic, uxeSad Tu vityviT, am zolis Sesa-bamisi dnm-is TanamimdevrobaTa iseTi TvisebebiT ganisazRvreba, rogoricaa fuZeebis Semcveloba (anu fuZeTa wyvilebis GC da AT-s procentuli Tanafardoba) da ganmeorebadi dnm-is elementebis ganawileba. am da sxva e.w. bendirebis meTodebis gamoyenebiT SesaZlebeli xdeba individualuri qromosomebis amocnoba. garda amisa, advilad SeiZleba dadgindes qromosomebis struqturuli da ricxobrivi anomaliebi, romlebsac detalu-rad me-5 da me-6 TavebSi ganvixilavT.

miuxedavad imisa, rom specialistebis mier metafazuri qromosomebis analizi uSualod mik-roskopSi warmoebs, aseve miRebulia qromosome-bis amoWra mikrofotosuraTidan da maTi wyvile-bad dalageba klasifikaciis standartuli wesiT, rogorc es sur. 2-12-ze aris naCvenebi. aseT suraTs kariotipi ewodeba. cneba kariotipskidev iye-neben individualuri an saxeobrivi qromosomuli nakrebis aRsaniSnavad (mag. mamakacis normaluri kariotipi an adamianis kariotipi), kari-otipirebas ki xmaroben rogorc zemoaR werili suraTis misaRebi procesis amsaxvel cnebas.

im qromosomebisagan gansxvavebiT, romlebic moCans SeRebil preparatebze mikroskopSi an fotosuraTebze, cocxali ujredis qromosomebi blanti da dinamiuri struqturebia. mitozis mim-dinareobis dros TiToeuli interfazuli qroma-tini SesamCnevad kondensirdeba (sur. 2-12). pro-fazaSi, rodesac qromosomebi mikroskopSi gamo-Cenas iwyeben, 1-eli qromosomis sigrZe (romelic dnm-is daaxloebiT 250 milion fuZeTa wyvils Seicavs) kondensirebis Sedegad daaxloebiT 50 mikrometri xdeba. metafazaSi, maqsimaluri kon-densaciis pirobebSi, qromosomebis dnm-is sig-rZe gaWimul mdgomareobaSi misi sawyisi sigrZis 1/10000-s Seadgens. rodesac qromosomebs zolebis gamovlenis mizniT Rebaven (ix. sur. 2-11 da 2-12), miRebul preparatze (yvela qromosomaze gada-angariSebiT) jamSi 1000 da meti zolis (bendis) garCeva SeiZleba. maSasadame, TiToeuli cito-genetikuri zoli 50 an met gens Seicavs. mitozis dasrulebis Semdeg qromosomebi dekondensir-deba, interfazul birTvSi Tavis sawyis mosvene-bul mdgomareobas ubrundeba da ukve rogorc interfazuli birTvis qromatini, emzadeba axali ujreduli ciklis dasawyebad (sur. 2-13).

meiozi

meiozi aris ujredis dayofis procesi, rom-lis Sedegadac diploiduri ujredebi dasabams aZleven haploidur gametebs, is Seicavs ujredis gayofis unikalur tips, romelic mxolod germi-naciul ujredebs axasiaTebs. meiozi moicavs dnm-is sinTezis erT cikls, rasac mosdevs qromosome-bis segregaciis da ujredis gayofis ori cikli (sur. 2-12). is germinaciuli ujredebi, romlebic gadian meiozs pirveladi spermatocitebi da pirveladi oocitebi zigotidan warmoiqmnebian meiozis dawyebamde mravlobiTi mitozebis seriis gavlis Sedegad.

mamakacisa da qalis gametebs sxvadasxva war-moSoba aqvs. miuxedavad imisa, rom movlenebis Tanamimdevroba msgavsia, am movlenebis gansaxor-cieleblad saWiro dro gansxvavebulia. ori, erTmaneTis momdevno meiozuri gayofis process, Sesabamisad I meiozs da II meiozs uwodeben. I meiozi cnobilia reduqciuli gayofis saxelwodebiT, I meiozis profazaSi homologebis dawyvilebis da anafazis dasrulebisas Svileul ujredebSi maTi segregaciis gamo, qromosomebis ricxvi diploi-duridan haploiduramde mcirdeba. X da Y qro-mosomebi erTmaneTis homologebi ar arian, maT mxolod mokle da grZeli mxris boloebSi aqvT homologiuri segmentebi (ix. me-6 Tavi) da daw-yvilebisas I meiozSi maTi SeerTeba swored am ubnebSi xdeba.

I meiozi imiTac aris saintereso, rom am sta-diaSi mimdinareobs genetikuri rekombinacia (mas meiozur krosingovers uwodeben). homologiuri qromosomuli wyvilis araSvileul qromatidebs Soris xdeba dnm-is homologiuri ubnebis gacvla, rac meiozis Sedegad mxolod da mxolod ara-


sur. 2-12 gimziT (G-bendirebis meTodiT) SeRebili mamakacis kariotipi. qromosomebi arian mitozis prometa-fazur stadiaze da dawyobili arian standartuli klasifikaciiT sigrZis mixedviT 1-idan 22-mde; X da Y qromo-somebi calkea naCvenebi. (Courtesy of Stuart Schwartz, University Hospitals of Cleveland, Ohio.)

identuri gametebis warmoqmnas uzrunvelyofs. memkvidrul daavadebebze pasuxismgebeli genebis rukis Sedgenisas genetikur rekombinacias prin-cipuli mniSvneloba eniWeba. am sakiTxs detalu-rad me-10 TavSi ganvixilavT. I meiozSi, rekom-binaciis dros, xdeba ori homologiuri qro-mosomis urTierTCaxveva garkveul wertilebSi, rasac gansakuTrebuli mniSvneloba aqvs rekom-binantuli qromosomebis swori segregaciisaT-vis. araswori rekombinacia meiozis dros iwvevs qromosomebis segregaciis darRvevas, rac xSirad sxvadasxva qromosomuli anomaliis (magaliTad, daunis sindromis) mizezad gvevlineba (ix. me-5 da me-6 Tavi).

I meiozs mosdevs II meiozuri gayofa. I da II meiozur gayofas Soris xanmokle intervalSi ar xdeba dnm-is replikacia, rogorc amas, Cveu-lebriv, adgili aqvs mitozis dros. qromatidebi iseve dacalkavdebian, rogorc mitozis dros da yoveli qromosomis TiTo qromatida gadadis Svileul ujredSi (sur. 2-14).

pirveli meiozuri gayofa (I meiozi)

profaza I. meiozi I-is profaza rTuli procesia, romelic gansxvavdeba mitozuri profazisagan mTeli rigi TaviseburebebiT da genetikuri Sede-gebiT. mTeli profazis ganmavlobaSi qromosome-bi ganuwyvetliv kondensirdebian, mokldebian da wyvildebian (sur. 2-15).

leptonema. qromosomebi, romlebmac ukve gani-cades replikacia S fazaSi, xiluli xdebian moCanan wvrili Zafebis saxiT da iwyeben konden-sacias. adreul stadiaSi TiToeuli qromosomis ori Svileuli qromatida erTmaneTs ise mWidrod ekvris, rom maTi garCeva SeuZlebelia.

zigonema. am stadiaSi homologiuri qromosome-bi sigrZivad wyvildebian. dawyvilebis es pro-cesi, anu sinafsisi, Cveulebriv, Zalian zustia da uzrunvelyofs Sesabamisi dnm-is Tanamimdevrobe-bis saTanado urTierTganlagebas mTeli qromo-somis sigrZis gaswvriv.

miuxedavad imisa, rom sinafsisis moleku-luri safuZvlebi bolomde garkveuli ar aris, eleqtronul mikroskopze Cans, rom qromosome-bis urTierTkavSirs uzrunvelyofs sinaftone-maluri kompleqsi, lentiseburi cila-Semcveli struqtura (sur. 2-16). sinaftonemaluri kompleq-si arsebiT rols TamaSobs rekombinaciis pro-cesSi.paqinema. am stadiis ganmavlobaSi qromosomebi kidev ufro Caixveva. sinafsisis formireba das-ruldeba da gamoikveTeba homologebis calkeu-li wyvili, rogorc bivalenti (zogjer maT tet-radas uwodeben oTxi qromatidis Semcvelobis gamo). paqinemis stadiaSi xdeba meiozuri krosin-goveri (ix. sur. 2-15).diplonema. rekombinacias mosdevs sinaftonema-luri kompleqsis daSla da TiToeuli bivalen-tis ori komponentis urTierTdacalkaveba. sabo-

1 2 3 4 5

6 7 8 9 10 11 12

13 14 15 16 17 18

19 20 21 22

sasqeso qromosomebi


sur. 2-13 qromosomis kondesacia-dekondesacia ujreduli ciklis sxva-dasxva stadiaze.

interfazuli birTvi

dekondensirebuli qromatini

kondensacia mitozissawyis etapze

profaza

metafazadekondensaciaujredis interfazaSi dabrunebisas

sur. 2-14 meiozis ZiriTadi etapebis gamartivebuli sqema. moicavs dnm-is replikaciis erT cikls da qromo-somebis segregaciis or cikls, I meiozs da II meiozs.

qromosomis replikacia

I meiozi

II meiozi

oTxi haploiduri gameta

lood, TiToeuli bivalentis ori homologi SekavSirebulia mxolod qiazmebis (jvaredini struqturebis) wertilebSi. miiCneven, rom qiaz-mebi Seesabameba krosoverul ubnebs. adamianis spermatocitSi 50-mde qiazmaa, anu ramdenime jva-redini struqtura TiToeul bivalentze. diakinezi. am stadiaSi qromosomebi maqsimalur kondensacias aRweven.

I metafaza mitozis msgavsad I metafazac birTvuli membranis darRvevis Semdeg iwyeba. TiTistara formirdeba da qromosomuli wyvilebi ekvato-rul sibrtyeSi damwkrivdebian ise, rom maTi centromerebi sxvadasxva polusebiskenaa orien-tirebuli.

I anafaza I anafazis mimdinareobisas yoveli bivalenturi struqturis ori wevri erTmaneTs Sordeba da centromerebiT (romlebic Svileul qromatidebs akavSireben urTierTTan) ujredis sapirispiro polusebisaken miizideba. am process gaTiSva ewodeba (ix. sur. 2-15). amrigad, qromo-somebis ricxvi naxevrdeba da I meiozis Sedegad warmoqmnil TiToeul ujreds qromosomebis haploiduri raodenoba eqneba. bivalenturi struqturebi erTmaneTisagan damoukideblad dajgufdeba da, aqedan gamomdinare, sawyisi ma mi-seuli da dediseuli qromosomuli kompleqtebi SemTxveviTi kombinaciebis safuZvelze da xa-risxdeba. 23 qromosomuli wyvilis SesaZlo kombinaciaTa ricxvi, romelic gametebSi xvdeba, 8 milions aRemateba (223). realurad, krosingo-ve ris procesis gamo, genetikuri masalis SesaZ-lo variaciebis raodenoba, romelic mSoblebi-dan Svils gadaecema, mniSvnelovnad Warbobs am ricxvs. zemoaRwerili procesebis gamo, TiToeuli qromatida Seicavs segmentebs, romlebsac miiRebs mSobliuri qromosomuli wyvilis TiToeuli wevrisagan. magaliTad, am stadiaSi tipuri 1-eli qromosoma Sedgeba mamiseuli da dediseuli war-momavlobis sami-xuTi segmentisagan, romlebic Tanamonacvleoben (am sakiTxis damatebiTi gan-xilva ix. me-10 TavSi).


sur. 2-15 meiozisa da misi mimdinareobis sqematuri suraTi.Ggamosaxulia erTi qromosomuli wyvili da erTi krosingoveri, rac oTxi gansxvavebuli gametis warmoqmniT mTavrdeba.Qqromosomebi replicirdeba interfazis ganmavlobaSi da I meiozur profazaSi ujre-dis SesvlisTanave iwyebs kondesacias. I meiozis dros qromosomebi warmoqmnis sinafsur kavSirebs da rekom-binirebs. qiazmebi Cans I metafazis dros, homologebis centromerebi orientirebulia urTierTsapirispiro polusebisaken. I anafazaSi kargad Cans homologebs Soris urTierTgacvlili dnm-is fragmentebi.Hho-mologebi sapirispiro polusebisaken miemarTeba. I meiozisa da citokinezis damTavrebis Semdeg iwyeba II meiozi, romelic mitozuri gayofis msgavsad mimdinare-obs. II anafazaSi Svileuli kinetoqorebi dacalkevdeba da miemarTeba urTierTsapirispiro polusebisaken. warmoiqmneba oTxi haploiduri gameta.

II me

ioz

i

I mei

oz

i

interfaza I profaza

I metafaza

I anafaza

interfaza

II metafaza

II anafaza

gametebi

ujredis gayofis dros SeiZleba moxdes mravali Secdoma. zogierTi darRvevis gamo ujredebi ver daasruleben meiozs da iRupebian, sxvebi ki iwveven segregaciis darRvevas anafaza-Si. magaliTisTvis moviyvanT darRvevas, romlis drosac qromosomuli wyvilis orive homologi erTi polusisaken (da ara sapirispiro poluse-bisaken) miemarTeba. am paTogenur process gau-TiSvelobas uwodeben. (normaluri procesidan gadaxvevis Sedegebs me-5 da me-6 TavebSi ganvixi-lavT).

I telofaza telofazis stadiisaTvis qromosomaTa ori haploiduri nakrebi ujredis sapirispiro polusebTan aris Sejgufebuli.

citokinezi

I telofazas mosdevs ujredis gayofa or haploi-dur Svileul ujredad. iwyeba meiozuri interfa-za. spermatogenezis dros citoplazma or Svile-ul ujredSi TiTqmis Tanabrad gadanawildeba (sur. 2-17). oogenezis dros citoplazmas TiTqmis mTlianad miiRebs erTi ujredi, xolo meore (meoreuli oociti) pirvel polarul sxeulad gadaiqceva (sur. 2-18). mitozisagan gansxvavebiT, interfaza xanmoklea da mas II meiozi mosdevs. meiozuri da mitozuri interfazebi erTmaneTi-sagan imiT gansxvavdeba, rom meiozur gayofebs Soris ar aris S faza (rac niSnavs, rom aq ar xde-ba dnm-is sinTezi).

meore meiozuri gayofa (II meiozi)

meore meiozuri gayofa mitozis msgavsia. gansxvave-ba mxolod isaa, rom ujredi, romelic II meiozSi Sedis, qromosomebis haploidur kompleqts Sei-cavs. am procesis saboloo produqtia oTxi ujre-di, romelTagan TiToeuli 23 qromosomas Seicavs (ix. sur. 2-15). rogorc zemoT aRvniSneT, krosin-goveris gamo, romelic I meiozSi xdeba, warmoq-mnili gametebi Seicavs araidentur qromosomebs. homologiuri wyvilis TiToeuli dediseuli da mamiseuli qromosoma SemTxveviT segregirdeba Svileul ujredebSi I meiozis dros. meiozis mim-


sur. 2-16 meiozis procesSi warmoqmni-li adamianis pirveladi spermatocitis eleqtronuli mikrografia; naCvenebia 22 autosomuri sinaftonemaluri kompleqsi da XYqromosomuli wyvili (naCvenebia isriT). calkeuli bivalentis dnm ar moCans, magram gaWimulia lateralurad sinaftonemaluri kompleqsis sxvadasxva mxares. (Courtesy of A. C. Chandley, Western General Hospital, Edinburgh, Scotland.)

dinareobis dros xdeba agreTve TiToeuli genis mamiseuli da dediseuli alelebis segregacia; magram is, Tu rodis xdeba alelebis segregacia I Tu II meiozuri gayofis dros (ix. CarCoSi moce-muli teqsti), damokidebulia krosingoverSi maT monawileoba-armonawileobaze.

meiozis genetikuri Sedegebi

gametebis formirebis ZiriTadi etapia qromoso-maTa ricxvis reduqcia diploiduridan haplidu-

ramde; es gametebis formirebis ZiriTadi etapia.

alelebis segregacia I an II meiozis dros, mende-lis pirveli kanonis mixedviT.

genetikuri masalis gadanawilebas homologebis sortirebis SemTxveviTi xasiaTi ganapirobebs,

rac Seesabameba mendelis meore kanons.

krosingoveriT gamowveuli genetikuri masalis damatebiTi gadanawileba, savaraudod, qmnis gene-

tikuri mravalferovnebis safuZvels. amasTan,

misi normaluri mimdinareoba gansakuTrebiT

mniSvnelovania qromosomebis sworad gaTiSvis-

Tvis.

adamianis gametogenezi da ganayofiereba

adamianis primordialuri Canasaxovani ujre-debis garCeva yviTris parkis entodermaSi meo-Txe kviridan aris SesaZlebeli. meeqvse kviris gan mav lobaSi ujredebi migrireben genitaluri borcvisaken, ukavSirdebian somatur ujredebs da yalibdeba primitiuli gonadebi, romlebic male-ve diferencirdebian saTesleebad an sakvercxee-bad, rac, Tavis mxriv, damokidebulia ujredebSi sasqeso qromosomebis (XY an XX) Semcvelobaze.

dawvrilebiT am sakiTxebs me-6 TavSi SevexebiT. spermatogenezic da oogenezic moicavs meiozur gayofebs, Tumca maT Soris arsebobs mniSvne-lovani gansxvavebebi, romlebic Seexeba meiozis detalebs da xangrZlivobas, rasac STamomavlo-bisaTvis SesaZloa mohyves seriozuli klinikuri da genetikuri Sedegebi. qalebSi meiozis inicia-cia mxolod erTxel xdeba, nayofis ganviTarebis adreul stadiaze iwyeba da ujredebis SezRudu-li raodenobis warmoqmniT mTavrdeba. mamakace-bSi ki meiozis procesi gansxvavebulad mimdina-reobs. misi iniciacia ganuwyvetliv xdeba dayofa-di ujreduli populaciis erTdroulad mraval ujredSi da grZeldeba zrdasrul asakSi.

adamianis meiozis procesze uSualo dakvirve-ba rTulia. qalebSi meiozis stadiebi jer nayo-fis sakvercxeSi mimdinareobs, Semdeg oocitSi, ovulaciis wina periodSi, bolo stadia ki ukve ganayofierebis Semdgom. postovulaciuri sta-diebis Seswavla SeiZleba in vitro, xolo sawyisi stadiebis mimarT amis SesaZlebloba SezRudu-lia. mamakacebSi meiozis SeswavlisaTvis saWiro masalis saTeslidan miReba arc ise rTulia, rad-gan saTeslis biofsia gamokvlevis im meTodebis CamonaTvalSi Sedis, romlebsac specializebul klinikaSi mamakacis uSvilobis mizezis dasadge-nad mimarTaven. bevri ram jer kidev gasarkvevi rCeba im citogenetikuri, bioqimiuri da moleku-luri meqanizmebis Sesaxeb, romlebic meiozis normalur msvlelobas warmarTavs, da pasuxis-mgebelia meiozuri darRvevebis mizezebsa da Sedegebze.

spermatogenezi

spermatogenezis stadiebi gamosaxulia me-2-17 suraTze. spermatozoidebi formirdeba saTes-le jirkvlis milakebSi. milakebi amofenilia spermatogoniumebiT, romlebic diferenciaciis sxvadasxva stadiaze imyofebian. isini primor-


II me

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I me

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sur. 2-17 adamianis spermatogenezis amsaxveli sqema ori meiozuri dayofiT. ganviTarebis procesi iwyeba sqesobrivi momwifebis asakSi da grZeldeba daaxloe-biT 64 dRes. naCvenebia qromosomaTa ricxvi (46 an 23) da sasqeso qromosomebis (X da Y) Semcveloba Ti-Toeul ujredSi. (Modified from Moore KL, Persaud TVN: The Developing Human: Clinically Oriented Embryology, 6th ed. Phila-delphia, WB Saunders, 1998.)

saTeslejirkvali

spermatogoniumebi46,XY

pirveladi spermatociti 46,XY

meoradi spermatocitebi

spermati-debi

dialuri germinaciuli ujredebidan ganviTar-dnen mravali mitozuri gayofis Sedegad. sperma-togoniumebis mravaljeradi mitozuri gayofis Sedegad formirdeba pirveladi spermatocitebi, romlebic ganicdian I meiozur dayofas da yali-bdeba haploiduri meore rigis spermatocitebi. isini swrafad gaivlian meore meiozur dayofas da TiToeulidan ori spermatida formirdeba, romlebic ganicdian diferencirebas Semdgomi dayofis gareSe da Camoyalibdebian spermato-zoidebad. adamianSi mTlianad am process 64 dRe sWirdeba. xdeba mravalricxovani spermatozoi-debis warmoqmna. eakulati 200 milionamde sper-matozoids Seicavs. gamoTvlilia, rom mamakaci Tavis sicocxlis ganmavlobaSi daaxloebiT 1012 spermatozoids warmoqmnis, rac ramdenime aseul mitozur dayofas moicavs.

oogenezi

spermatogenezisagan gansxvavebiT, romelic zrdasrul asakSi mimdinareobs, oogenezi prena-taluri ganviTarebis periodSi iwyeba (ix. sur. 2-18). kvercxujredebis ganviTareba xdeba oogo-niumebidan. oogoniumebi sakvercxis qerqovani Sris ujredebia, romlebic primordialuri ger-minaciuli ujredebidan 20-mde mitozuri gayofis Sedegad miiReba. TiToeuli oogoniumi ganviTa-rebadi folikulis centralur ujreds warmoad-gens. prenataluri ganviTarebis daaxloebiT me-3 TvisaTvis embrionis oogoniumebisagan viTarde-ba pirveladi oocitebi, romelTa umravleso-ba ukve Sesulia I meiozis profazaSi. oogenezis procesi asinqronulad mimdinareobs da nayofis sakvercxeSi Tanaarsebobs adreuli da gviani stadiebi. dabadebis momentisaTvis sakvercxeebSi ramdenime milioni oocitia, magram maTi umrav-lesoba degeneracias ganicdis da sabolood mxo-lod 400 maTgani momwifdeba. dabadebis momenti-saTvis I profazaSi pirveli rigis yvela ooci-ti Sedis da misi nawili, romelic gadaurCeba degeneracias, aTwleulebis ganmavlobaSi rCeba am stadiaze, sanam ovulacia kidev rCeba qalis menstrualuri ciklis nawilad.

individualuri folikulebis momwifeba qalis sqesobrivi momwifebis asakidan iwyeba. momwi-febis periodSi pirveli rigis oociti orjer iyofa; TiToeuli oociti swrafad amTavrebs I meiozs da ise iyofa, rom miRebuli ori ujredi-dan erTi gadaiqceva meore rigis oocitad (anu kvercxujredad), romelic pirveli rigis ooci-tidan citoplazmis udides nawils da organele-bs miiRebs, xolo meore ujredi pirvelad mimar-TulebiT sxeulaks warmoqmnis (ix. sur. 2-18). amis Semdeg maSinve Odaiwyeba II meiozi, romelic ovu-laciis ganmavlobaSi gaivlis metafazur stadias, Tumca misi dasruleba mxolod ganayofierebis Semdeg moxdeba.

23,X 23,Y

23,X 23,X 23,Y 23,Y

23,X 23,X 23,Y 23,Y


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I

meio

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sur. 2-18 adamianis ori meiozuri dayofis momcveli oogenezis da ganayofierebis sqema.Ppirveladi ooci-tebi formirdeba prenatalur periodSi da wlobiT Se-Cerdeba I meiozuri dayofis profazaSi sqesobrivi mom-wifebis dawyebamde. folikulis momwifebisasOoociti daasrulebs I meiozs. Sedegad miiReba meoradi oociti da pirveli mimarTulebiTi sxeulaki. ovulaciis Sem-deg TiToeuli oociti daasrulebs II meiozis meta-fazas. II meiozi dasruldeba mxolod im SemTxvevaSi, Tu moxdeba ganayofiereba. ganayofierebis Sedegad miiReba ganayofierebuli kvercxujredi da meore mi-marTulebiTi sxeulaki.

sakvercxe

pirveladi oociti folikulSi

SeCerebuli I profazisstadiaze sqesobrivimomwifebis dawyebamde

meoradi oociti meiozuri TiTistara

pirveladi mimarTulebiTi sxeulaki

ovulacia

ganayofiereba

meoremimarTulebiTi sxeulaki

spermatozoidi

momwifebuli kvercxujredi

ganayofiereba

kvercxujredis ganayofiereba, Cveulebriv, falo-pis milSi, ovulaciis momentidan erT an ramde-nime dReSi SeiZleba moxdes. spermatozoidebis auracxeli raodenobis miuxedavad, erTi sperma-tozoidis kvercxujredSi SeRwevis Semdeg iwyeba bioqimiur cvlilebaTa mTeli seria, rac xels uSlis sxva spermatozoidebis ujredSi SeWras.

ganayofierebis Semdeg meoreuli mimarTule-biTi sxeulakis formirebiT dasruldeba II meio-zi (ix. sur. 2-18). ganayofierebuli kvercxujredi, masSi moxvedrili spermatozoidis qromosomebiT, warmoqmnis pronukleuss, romelic birTvuli membraniTaa SemosazRvruli. ganayofierebisTa-nave diploiduri zigotis qromosomebi replici-reben da zigota mitozur dayofas daiwyebs, raTa warmoqmnas ori Svileuli diploiduri ujredi. am mitozuri dayofiT iwyeba danawevreba da xdeba embrionis ganviTarebis iniciacia (ix. me-14 Tavi).

miuxedavad imisa, rom ganviTareba zigotidan (Casaxvidan) iwyeba. klinikur medicinaSi orsulo-bis stadiebs da xangrZlivobas, Cveulebriv, e.w. menstrualuri asakiT gansazRvraven, romelic qalis bolo menstrualuri periodidan (Casaxvam-de daaxloebiT 14 dRiT adre) aiTvleba.

mitozisa da meiozis samedicino mniSvneloba

mitozisa da meiozis biologiuri mniSvneloba imaSi mdgomareobs, rom uzrunvelyos qromoso-muli ricxvis mudmivoba ujredisa da organizmis TaobebSi. am procesebis samedicino mniSvnelobas gansazRvravs Secdomebi, romlebic ujredis dayo-fis erT an meore meqanizmSi xdeba da qromosoma-Ta anomaliuri ricxvis matarebeli individebis an ujreduli xazebis ganviTarebas ganapirobebs.

rogorc amas detalurad ganvixilavT me-5 TavSi, meiozuri gauTiSveloba, gansakuTrebiT oogenezSi, adamianSi yvelaze ufro gavrcelebu-li mutaciuri meqanizmia, romelic orsulobis SemTxvevebSi yvelaze xSirad iwvevs qromosomu-li anomaliis matarebeli nayofebis ganviTare-bas. orsulobaTa im SemTxvevebs Soris, romlebic drouli mSobiarobiT mTavrdeba, qromosomuli anomaliebi axalSobilebSi Tandayolili defeq-tebis, zrda-ganviTarebis Seferxebisa da gonebri-vi CamorCenilobis umTavresi mizezia.

genetikuri daavadebis mizezi SeiZleba mito-zuri gauTiSvelobac iyos. ganayofierebis Sem-deg mitozurma gauTiSvelobam rogorc ganviTa-rebad embrionSi, ise eqstraembrionul qsovile-bSi, kerZod, placentaSi, SeiZleba qromosomuli mozaicizmi gamoiwvios, rac safuZvlad udevs, magaliTad, daunis sindromis mozaikuri formis ganviTarebas. garda amisa, qromosomebis segre-gacia swrafad dayofad qsovilebSi, rogoricaa msxvili nawlavis ujredebi, xSirad qromosomu-li darRvevebis matarebeli simsivneebis warmo-


Sobis erT-erTi mizezia. Sesabamisad, mravali sim-sivnis SemTxvevaSi qromosomebis balansis Sefa-seba mniSvnelovan sadiagnostiko da saprognozo testad iTvleba.

ZiriTadi literatura

Brown TA: Genomes, 3rd ed. New York, Garland, 2007. Miller OJ, Therman E: Human Chromosomes, 4th ed. New York,

Springer-Verlag, 2001. Moore KL, Persaud TVN: Developing Human: Clinically Oriented

Embryology, 7th ed. Philadelphia, WB Saunders, 2003.

specialuri literatura calkeuliTemis irgvliv

Deininger PL, Batzer MA: Alu repeats and human disease. Mol Genet Metab 67:183-193, 1999.

International Human Genome Sequencing Consortium: Initial sequencing and analysis of the human genome. Nature 409:860-921, 2001.

International Human Genome Sequencing Consortium: Finishing the euchromatic sequence of the human genome. Nature 431:931-945, 2004.

Kazazian HH, Moran JV: The impact of L1 retrotransposons on the human genome. Nat Genet 19:19-24, 1998.

Trask BJ: Human cytogenetics: 46 chromosomes, 46 years and count-ing. Nat Rev Genet 3:769-778, 2002.

Venter JC, Adams MD, Myers EW, et al: The sequence of the human

genome. Science 291:1304-1351, 2001.

vebgverdebi

Human Genome Resources: A compilation of useful websites for the study of genes, genomes and medicine. http://www.ncbi.nlm.nih.gov/genome/guide/human/

University of California, Santa Cruz: Genome Bioinformatics. http://genome.ucsc.edu/

Ensembl genome browser: European Bioinformatics Institute/ Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. http://www.ensembl.org/Homo_sapiens/index.html

s a v a r j i S o e b i

1. garkveul lokusSi adamians aqvs ori aleli, A da

a.a) rogoria am adamianis gametebis genotipi?

b) rodis xdeba A da a segregacia: a) Tu qromo-somis lokussa da centromers Soris ar xdeba

krosingoveri; b) Tu qromosomis lokussa da

centromeras Soris xdeba erTi krosingove-

ri.

2. ra aris adamianSi raodenobrivi qromosomuli

darRvevebis mTavari mizezi?

3. ra iwvevs genetikuri mravalferovnebis gazrdas,

Tu gamovricxavT krosingovers; SeafaseT, rogo-

ri iqneba albaToba, Tu Tqven yvela qromosoma

miRebuli gaqvT mamis dedisagan an dedis dedisa-

gan. rogori iqneboda Tqveni sqesi, mdedrobiTi

Tu mamrobiTi?

4. meiozis dros qromosoma Sedgeba ori qromatidi-

sagan da TiToeuli maTgani dnm-is erT moleku-

las Seicavs.

a) ramdeni qromosoma da ramdeni qromatida

iqneba adamianis TiToeul ujredSi I meiozis

bolos?

b) ramdeni qromosoma da ramdeni qromatida

iqneba TiToeul ujredSi II meiozis bolos?

g) rodis aRdgeba qromosomaTa diploiduri

nakrebi? rodis aRdgeba tipuri metafazuri

qromosomis orqromatidiani struqtura?

5. ixelmZRvaneleT me-2-8 suraTiT da gamoTva-

leT, ramden gens SeiZleba moicavdes miliona-

mde fuZeTa wyvili 1-el, me-13, me-18, me-19, 21-e da

22-e qromosomebSi. romel qromosomaSi momxdar

Tanabari zomis qromosomul darRvevebs eqneba

meti klinikuri efeqti, me-18 Tu me-19 qromosoma-

Si? 21-e Tu 22-e qromosomaSi?

Tavi 3 adamianis genomi: genebis struqtura da funqcia 25

molekulur doneze genisa da qromosomis struq-turisa da funqciis kvlevam ukanaskneli 20 wlis ganmavlobaSi mniSvnelovani progresi ganicada, rasac bolo periodSi Tan daerTo dnm-is nuk-leotidur TanamimdevrobaTa detaluri analizi adamianis genomis organizaciis ufro Rrmad Ses-wavlis mizniT. miRwevebi metwilad ganapiroba klinikaSi molekuluri genetikis da genomikis danergvam, riTac safuZveli Caeyara samedicino genetikisadmi axal, gansxvavebul midgomas. am TavSi SemogTavazebT adamianis genomis organiza-ciisa da molekuluri genetikis zogierTi aspeqtis mimoxilvas, romelic genetikisa da medicinis urTierTdamokidebulebis garkvevaSi dagvexma-reba. winamdebare Tavi ar isaxavs miznad genis struqturisa da regulaciis Sesaxeb dagrovili axali monacemebis detalur ganxilvas. aq mowo-debuli informacia me-4 TavSi iqneba Sevsebuli Tanamedrove molekuluri genetikis eqsperimen-tuli meTodebiT, rasac eqneba gansakuTrebuli praqtikuli mniSvneloba da dagvexmareba ukeT gaverkveT adamianis da samedicino genetikis sa -kiTxebSi.

genebze da genomis organizaciaze dagrovilma informaciam mniSvnelovani gavlena moaxdina ada-mianis ukeT Secnobaze medicinis da fiziologiis TvalsazrisiT. rogorc 1980 wels nobelis premi-is laureati pol bergi aRniSnavda:

dResdReobiT Cveni samedicino codna da am codnis praqtikuli gamoyeneba adamia-nis anatomiis, fiziologiis da bioqimiis sofistikur codnas eyrdnoba. magram moma-valSi, daavadebebTan brZolisaTvis Cven dagvWirdeba adamianis genomis, moleku-luri anatomiis, bioqimiisa da fiziologiis detaluri codna da ufro Rrma gaazreba imisa, Tu rogoraa organizebuli adamianis genebi da rogor regulirdeba maTi funqcie-bi. amave dros eqimebi iseve gaTviTcnobie-rebuli unda iyvnen qromosomebis da genebis molekulur anatomiasa da fiziologiaSi,

rogorc kardioqirurgi gulis struqturasa da funqciaSi~.

adamianis genomis informaciuli Seneba

rogor axerxebs adamianis genomis 3 miliardniS-niani cifruli kodi misi anatomiis, fiziologii-sa da bioqimiis urTulesi meqanizmebis marTvas, razec bergic mianiSnebda. am kiTxvaze pasuxi far-TomasStabur informaciul eqspansiaSi unda ve-ZioT, romlis moqmedebas mudam vgrZnobT genomis genebidan proteomis cilebis Secnobisaken mima-val gzaze. proteomis cilebi kargad awyobili orkestriviT aamoqmedeben ujredebis, organoe-bis da mTliani organizmis mravlobiT funqciebs da akontroleben maT urTierTobas garemosTan. miuxedavad imisa, rom dRes Cven ukve vflobT codnas adamianis genomis arsebiTad srul Tana-mimdevrobaze, jer kidev zustad ar viciT genomSi arsebuli genebis ricxvi. dRevandeli gamoTvle-biT, genomi daaxloebiT 25 000 gens Seicavs, magram es cifri mxolod miniSnebaa kompleqsurobis im doneebze, romelTa gamovlenas cifruli infor-maciis dekodirebisas unda movelodeT (sur. 3-1).

rogorc Mme-2 TavSi aRvniSnavdiT, umetesi genebis produqts cila warmoadgens, romlis struqtura gansazRvravs mis specifikur funqcias ujredSi. magram genebsa da cilebs Soris marti-vi Sesabamisoba rom iyos (erTi-erTTan), maSin, yvelaze bevri, 25 000-mde saxis cila iarsebebda. es ricxvi aSkarad aradamajereblad gamoiyure-ba im mravalricxovani funqciebis asaxsnelad, romlebic adamianis ujreds axasiaTebs. am dile-maze pasuxs genis struqturisa da funqciis or TaviseburebaSi aRmovaCenT. pirveli: bevr gens aqvs unari, warmoqmnas ara erTi, aramed mrava-li gansxvavebuli cila (ix. sur. 3-1). es procesi, romelsac amave TavSi mogvianebiT ganvixilavT,

adamianis genomi: genebis struqtura da funqcia

3T a v i


sur. 3-1 genetikuri informaciis amplifikacia genomidan proteomaze, genur qselze da, sabolood, ujredul funqciebsa da fenotipze. mravali genomuri geni iyenebs alternatul makodirebel informacias mravlobiTi gan-sxvavebuli cilebis Sesaqmnelad. bevri cila monawileobas iRebs multigenur qselebSi, romlebic koordinire-bulad da kombinatorulad pasuxoben ujredul signalebs; es TavisTavad zrdis ujreduli funqciebis moqmedebis areals, rac organizmTa fenotips gansazRvravs. (Based on an original figure courtesy of Greg Wray, Duke University, Durham, North Carolina.)

genebSi arsebuli alternatiuli makodirebeli segmentebis gamoyenebiT da kodirebuli cilebis bioqimiuri modifikaciis gziT miiRweva. meore: individualuri cilebi TavisTavad ar funqcio-nireben. isini qmnian funqciaTa qsels, romelSic mraval sxva cilas CarTaven da koordinirebu-lad reagireben mravalricxovan da mravalfe-rovan genetikur, ganviTarebis mastimulirebel Tu garemo signalebze. genuri qselebis kombi-natoruli buneba ufro met mravalferovnebas sZens ujredul funqciebs. kompleqsuri genomis masStabiT, es ori Tviseba arsebuli informaciu-li resursis amplifikacias ganapirobebs. unda aRiniSnos, rom am SemTxvevaSi adamianis 25 000 gens milionamde gansxvavebuli cilis kodireba SeuZlia.

genebi lokalizebulia mTel genomSi, magram maT aqvT tendencia Sejgufdnen da Seqmnan klas-terebi zogierTi qromosomis garkveul ubnebSi. amis sailustraciod moviyvanT me-11 qromosomis magaliTs, romelic, rogorc es me-2 TavSi vnaxeT, SedarebiT mdidaria genebiT, maT Soris 1300-mde cila-makodirebeli geniT (ix. sur. 2-8). es genebi SemTxveviTad ar arian ganawilebuli qromoso-mis gaswvriv, aramed Tavmoyrili arian qromo-somis or garkveul ubanSi, sadac genebis simWid-rove imdenad maRalia, rom yovel 10kb-ze erTi geni modis (sur. 3-2). zogierTi geni monaTesave genebTan erTad qmnis ojaxebs, rasac ufro sru-lad qvemoT, amave TavSi ganvixilavT. sxva ubnebi Raribia genebiT da isini milioni da meti fuZe-Ta wyvilis momcvel, genebisagan Tavisufal e.w. udabur adgilebs warmoadgenen.

autosomuri genebi or calad arian war-modgenili: erTi asli moTavsebulia dedisgan memkvidreobiT miRebul qromosomaSi da meore mamisgan miRebul qromosomaSi. autosomuri gene-bis umetesoba eqspresirdeba da warmoqmnis pro-duqts. Tumca genomSi arsebobs mcirericxovani gamonaklisic, gadaxveva ZiriTadi kanonzomiere-bidan, rodesac genis ori aslidan mxolod erTi eqspresirebs. genetikuri regulaciis am uCveulo magaliTs genomur imprintings uwodeben da mis samedicino mniSvnelobas ufro detalurad ganvi-xilavT qvemoT, amave TavSi, agreTve me-5 da me-7 TavebSi.

centraluri dogma: dnm rnm cila

Tu rogor gansazRvravs genomi funqciur mraval-ferovnebas, naCvenebia me-3-1 suraTze. rogorc naCvenebia wina TavSi, eukariotul ujredebSi genetikuri informacia aris dnm-Si, dnm moTav-sebulia qromosomebSi, qromosomebi birTvSi; xolo cilebis sinTezi, procesi, romlis saSuale-biTac, faqtobrivad, xdeba genomSi kodirebuli informaciis ujreduli funqciebis gansazRvri-saTvis gamoyeneba, citoplazmaSi mimdinareobs. zemoaRniSnuli kompartmentizaciidan ki gamomdi-nareobs is faqti, rom adamiani eukariotuli organizmia. es, Tavis mxriv, gulisxmobs, rom ada-mianis ujredebs aqvT dnm-is Semcveli WeSmariti birTvi, romelic membraniT aris gamoyofili

anatomia fiziologia qceva

metabolizmi signalebis moZraoba mitozi adhezia pasuxi stresze

organizmi

organizmisfenotipi

ujredisfunqcia

genuri qseli

proteoma

genomi

Tavi 3 adamianis genomi: genebis struqtura da funqcia 27

sur. 3-2 me-11 qromosomis genuri Seneba, romelic 134,45 mgb dnm-isagan Sedgeba. A, naCvenebia genebis ganawileba qromosomis gaswvriv; genebi Tavmoyrilia qromosomis or ubanSi da mcire raodenobiTaa sxva ubnebSi. B, 5.1-5.3 mgb-is zomis ubani gadidebuli saxiT (azomilia mokle mxris telomeridan), romelic 10 gens Seicavs; maTgan xuTi ynosvis receptoruli genebis jgufs ekuTvnis, xuTi ki globinis genebis jgufs. C, xuTi b-msgavsi globinis geni (gadidebuli suraTi). (Data from European Bioinformatics Institute and Wellcome Trust Sanger Institute: Ensembl v37, February 2006, http://www.ensembl.org/Homo_sapiens/mapview?chr=11.)

sur. 3-3 pirimidinis fuZe uracili da rnm-Si Sema-vali nukleotidis struqtura. SeniSneT, rom dnm-is Saqari dezoqsiriboza Canacvlebulia Saqari riboziT. SeadareT me-2-2 suraTs.

citoplazmisagan. eukariotebisagan gansxvavebiT, prokariotebis (magaliTad, nawlavis baqteria

Escherichia coli-s) dnm ar aris gamoyofili birTvuli membraniT. eukariotuli ujredebis kompartmen-tizaciis gamo birTvidan citoplazmaSi genetiku-ri informaciis gadatana rTuli da kompleqsuri procesia. is molekuluri da ujreduli biolo-giis kvlevis sagans warmoadgens.

molekulur kavSirs or urTierTdakavSire-bul informaciul tips Soris (dnm genebis kodia, xolo aminmJava cilebis) uzrunvelyofs ribo-nukleinis mJava (rnm). rnm-is qimiuri struqtura dnm-is msgavsia, Tumca masSi dezoqsiriboza Cana-cvlebulia riboziT, Timinis nacvlad ki pirimi-dinis fuZe uracili (U) gvxvdeba (sur. 3-3). garda amisa, kidev erTi gansxvaveba dnm-sa da rnm-s Soris isaa, rom umetes organizmebSi rnm-is molekula erT-, dnm-is molekula ki orjaWviania.

informaciuli kavSirebi dnm-s, rnm-sa da ci-las Soris urTierTdamokidebulia: dnm gansaz-Rvravs rnm-is sinTezsa da mis nukleotidur Tanamimdevrobas, rnm polipeptidis sinTezs da aminmJavebis Tanamimdevrobas, xolo specifikuri cilebi monawileoben dnm-isa da rnm-is sinTezsa da metabolizmSi. informaciis am saxiT gadacemas molekulur biologiaSi centralur dogmas uwo-deben.

dnm-Si genetikuri informacia genetikuri kodis saxiT inaxeba, romelSic nukleotide-bis Tanamimdevroba gansazRvravs polipeptid-Si aminmJavebis Tanamimdevrobas. Tavdapirve-lad xdeba dnm-is matricidan rnm-is sinTezi, e.w. transkrifcia. am rnm-s ewodeba informaciuli rnm (i-rnm). i-rnm-s informacia birTvidan cito-plazmaSi miaqvs, sadac misi Tanamimdevroba deko-dirdeba, anu ganicdis translacias. translacia

ribosomebze mimdinareobs. isini citoplazmuri organelebia, romlebsac aqvs specialuri dasakav-Sirebeli adgilebi cilis sinTezSi monawile yve-la urTierTmoqmedi molekulisaTvis, maT Soris i-rnm-saTvis. ribosoma, Tavis mxriv, Sedgeba mra-vali sxvadasxva saxis struqturuli cilisagan da masTan asocirebuli specializebuli rnm-sagan, romelic ribosomuli rnm-is (r-rnm) saxeliTaa cnobili. translaciaSi monawileobs kidev mesame tipis rnm, e.w. transportuli rnm (t-rnm), rome-lic uzrunvelyofs molekulur kavSirs TiToeu-li i-rnm-is fuZeTa TanamimdevrobaSi Caweril kodsa da i-rnm-is mier kodirebuli cilis aminmJa-vur Tanamimdevrobas Soris.

centraluri dogmis Tanaxmad, mis komponen-tebzea damokidebuli informaciis gadatana. Sesa-bamisad, molekulur genetikaSi genis eqspresiis sakiTxebze msjeloba mizanSewonilia qvemoCamo-Tvlili sami informaciuli donidan erT-erTiT dnm-is, rnm-is an cilis ganxilviT daviwyoT. pirvelad ganvixilavT genis struqturas, rac genetikuri kodis transkrifciis da translaciis safuZvelia.

qromosoma11

genebi(#)

OR genebi

b-msgavsi globinis genebi

transkrifciis mimarTuleba

A

B

C

fuZe

uracili fosfati riboza


ruli ubani. is Seicavs transkrifciis dawyebaze pasuxismgebel Tanamimdevrobebs. 5' ubanSi aris dnm-is ramdenime elementi, romelTa Tanamimde-vroba konservirebulia sxvadasxva genSi. msof-lios mraval laboratoriaSi Catarebuli genis eqspresiis funqciuri kvlevis Sedegebi imaze miuTiTebs, rom es specifikuri konservirebuli elementebi mniSvnelovan rols asruleben regu-laciaSi. adamianis genomSi nanaxia promotore-bis ramdenime tipi gansxvavebuli regulatoru-li TvisebebiT, romlebic sxvadasxva qsovilSi garkveuli genebis eqspresiis dones da ganviTa-rebis suraTs gansazRvraven. individualuri kon-servirebuli promotoruli elementebis roli, romelic me-3-6 suraTzea gamosaxuli, ufro deta-lurad qvemoT iqneba ganxiluli genis eqspre-siis safuZvlebSi. promotorebi da sxva regula-toruli elementebi, romlebic genis 5' an 3' dabo-loebaze an genis intronebSia lokalizebuli, SesaZloa Seesabamebodes mutaciis saitebs gene-tikuri daavadebebis dros. am saitebs SeuZliaT Seaferxon genis normaluri eqspresia. regula-torul elementebs, maT Soris enhanserebs, sai-lenserebsa da lokusis makontrolebel ubnebs amave TavSi ganvixilavT ufro dawvrilebiT. am elementebidan zogierTi sakmaod daSorebulia genis makodirebuli ubnidan, rac ganamtkicebs mosazrebas, rom is genomuri garemo, romelSic geni arsebobs, misi evoluciisa da regulaciis ganmsazRvreli mniSvnelovani faqtoria. mxedve-lobaSia misaRebi genebis normalur eqspresiaze da funqciaze moqmedi mutaciebic. dRes, adamianis genomis proeqtis farglebSi SesaZlebeli gaxda da mimdinareobs mravali aTasi genis Sedarebi-Ti analizi, warmoebs damatebiTi mniSvnelovani genomuri elementebis identifikacia da ganixile-ba maTi roli adamianis daavadebebSi.

genis 3' boloze moTavsebulia mniSvnelovani aratranslirebuli ubani, romlis funqciaa mia-wodos signali momwifebuli i-rnm-s boloze ade-nozinis naSTebis Tanamimdevrobebis (e.w. poli-A kudi) damatebis Sesaxeb. miuxedavad imisa, rom aRiarebulia genis mezobeli regulatoruli Tanamimdevrobebic am genis nawilad iwodebodes, calkeuli genis zusti zoma mainc gaurkveveli rCeba manamde, sanam bolomde ar gairkveva Seda-rebiT dacilebul TanamimdevrobaTa funqciebi.

genuri ojaxebi

bevri geni erT ojaxSia gaerTianebuli nukleo-tidur TanamimdevrobaTa msgavsebis gamo an Ses

გენეტიკა (ტომპსონი და ტომპსონი)

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