
somatic mutation

somatic mutation anedi ankitamaina punarutpatti kanaalatoe kuudina bahula kana jeevula somatic sell yokka DNA kramamlo maarpu; antey, gamet, germ sell ledhaa gametocyte kakunda vaerae kanamlo sambhavinche edainaa mutation. oka jeevi yokka vaarasulaku sankraminchagala germline utparivartanala maadirigaa kakunda, saareeraka utparivartanalu saadhaaranamgaa vaarasulaku sankraminchavu. pratyaekamaina germline laeni mokkalalo mariyu canidarian genus "hydra" sabhyula maadirigaa molakettadam vanti yantraamgaala dwara alaingikamgaa punarutpatti cheyagala jantuvulalo eee vyatyaasam aspashtamgaa untundi.
saareeraka utparivartanalu oka jeevi yokka santaanaaniki sankraminchanappatiki, oke jeevi lopala oka kanam yokka vaarasulandarilo saareeraka utparivartanalu untaayi. aneka cancerlu perukupoyina saareeraka utparivartanala phalitamgaa untaayi.
prabhaavita kanaala yokka bhaagam.
somatic anae padam saadhaaranamgaa guddu ledhaa veeryaanni utpatti chese punarutpaadaka (germline) kanaalaku viruddhamgaa shareera kanaalanu suuchistumdi. udaaharanaku, ksheeradaalalo, saareeraka kanaalu antargata avayavalu, charmam, emukalu, raktam mariyu bandhana kanajaalam.
chaalaa jantuvulalo, somatic kanaala nundi suukshmakrimula kanaala vibhajana (suukshmakrimula abhivruddhi) abhivruddhi prarambha dasallo jarugutundi. pindamlo eee vibhajana sambhavinchina tarvaata, germline kanaala velupala edainaa utparivartana oka jeevi yokka santaanaaniki sankraminchadu.
ayithe, saareeraka utparivartanalu oke jeevilo utparivartana chendina kanam yokka anni santaanaalaku sankramistaayi. anduvalla oka jeevi yokka pradhana vibhagam adhe utparivartananu kaligi undavacchu, mukhyamgaa aaa utparivartana abhivruddhi prarambha dasalalo sambhavinchinatlayithe. oka jeevi jeevitamlo taruvaata sambhavinche somatic utparivartanaalanu gurtinchadam kashtam, endukante avi oke kanaanni matrame prabhaavitam cheyavachu-udaaharanaku, post-mytotic neuron; single sell sequencinglo merugudalalu somatic mutation adhyayanaaniki oka mukhyamaina sadhanam. kanaaniki chendina nuclear dna mariyu mitochondrial dna rendoo utparivartanaalanu koodabettukogalavu; somatic mitochondrial utparivartanalu konni neurodegenerative vyaadhula abhivruddhilo chikkukunnayi.
vaarasatvaaniki minahaayimpulu.
saareeraka utparivartanalu santaanam dwara vaarasatvamgaa pondalemu anae niyamaaniki aneka minahaayimpulu unnaayi. aneka jeevulu prarambha abhivruddhi samayamlo pratyeka suukshmajeevula rekhanu ketayinchavu. mokkalu mariyu spongelu mariyu pagadalu vanti besal jantuvulu badulugaa vayojana somatic kanajaalaalo pluripotent stem kanaala nundi gametlanu utpatti chestaayi. udaaharanaku, pushpinche mokkalalo, puula meristemloni vayojana somatic kanaala nundi suukshmakrimula kanaalu udbhavinchavacchu. nirneeta suukshmakrimula rekha laeni itara jantuvulalo tunicatelu mariyu flatwarmlu unnaayi.
gametla utpatti lekunda alaingikamgaa punarutpatti cheyagala jeevulalo saareeraka utparivartanalu kooda santaanaaniki sankraminchavacchu. udaaharanaku, niderian jaathi "hydra" looni jantuvulu molakettadam yokka vidhanam dwara alaingikamgaa punarutpatti cheyagalavu (avi laingikamgaa kooda punarutpatti cheyagalavu). hydralo, maatru hydraloni somatic kanaala nundi neerugaa kotta moggu abhivruddhi chendutundi. kumarte jeeviki daariteese kanajaalamlo unna mutation aaa santaanaaniki badilee cheyabadutundi.
aneka mokkalu sahajamgaa vrukshajanya punarutpatti dwara punarutpatti chestaayi-maatru mokka yokka oka mukka nundi kotta mokka perugudala-vittana utpatti dasha lekunda somatic utparivartanaalanu pracharam chestaayi. maanavulu krutrimamgaa antukattuta mariyu kaandam kotha dwara vrukshajanya punarutpattini prerepistaaru.
kaaranaalu.
germline utparivartanaala maadirigaane, dna replication mariyu marammattu samayamlo lopaalu mariyu saadhaarana cellular prakriyala dwara utpatti cheyabadina reactive oxygen jaatulaku gurikavadam vanti antarjana kaarakaala kaaranamgaa somatic kanaalalo utparivartanalu talettavachhu. utparivartana retunu penche utparivartana kaarakaalato parichayam dwara kooda utparivartanalu prerepinchabadavachhu.
chaalaa utparivartanaalu dna debbatinadam dwara panicheestaayi-pyrimidine diamers vanti dna nirmaanamloo maarpulu ledhaa okati ledhaa rendu dna tantuvulu virigipovadam. dna marammatu prakriyalu dna nashtalanu tolaginchagalavu, lekapothe, dna replication tarvaata, mutationku kaaranamavutundi. dna marammattu yokka yantraamgamlo porapaatlu nucleotide kramamlo maarpuku karanamainappudu ledhaa marammattu poortayye mundu replication sambhavinchinappudu mutation nashtam nundi vastundi.
utparivartanaalu bhouthikamgaa undavacchu, avi yuvi kiranaalu mariyu ex-kiranaala nundi vachhe radiation ledhaa rasayana anuvulu-dnatho neerugaa sankarshana chendhe anuvulu-pogaaku pogalo kanipinche saktivantamaina carcinogen ayina benzo ["eah"] pyrine yokka metabolitelu vantivi. cancer mariyu daani nivaarana gurinchi telusukovadaaniki cancerlaku sambandhinchina utparivartana kaarakaalanu tarachugaa adhyayanam chestaaru.
mutation frequency.
utparivartanala tarachudanam saadhaaranamgaa germline kanaala kante somatic kanaalalo ekkuvagaa untundani parisoedhanalu suuchistunnaayi; inca, germ mariyu somalo kanipinche utparivartana rakaalalo thedaalu unnaayi. oke jeevi lopala mariyu jaatula madhya vividha somatic kanajaalaala madhya utparivartana tarachudanamlo vaividhyam untundi.
milholland mariyu itarulu. (2017) maanavulalo mariyu elukalalo charma fibroblasts (oka rakamaina somatic sell) mariyu germline kanaala utparivartana retunu pariseelinchindi. vaaru single nucleotide variantla (snuvs) retunu kolicharu, veetilo ekkuva bhaagam replication error yokka parinaamam. utparivartana bhaaram (kanamlo unna mottam utparivartanalu) mariyu prati kana vibhajanaku utparivartana raetu (prati mitosisto kotta utparivartanalu) rendinti paramgaa, somatic utparivartana raetlu germline kante, maanavulalo mariyu elukalalo padhi retlu ekkuvagaa unnaayi.
maanavulalo, fibroblastlalo utparivartana load germline kante iravai retlu ekkuva (2.8 × 10−7 bays jataku 1.2 × 10−8 utparivartanaalato poliste). kana vibhajanala anchanaa sankhyalo vyatyaasaala kosam sardubaatu cheyabadina fibroblast utparivartana raetu suukshmakrimi kante 80 retlu ekkuvagaa undhi (varusaga, 2.66 × 10−9 verses. 3.prati mitosisku bays jataku 3 × 10−11 utparivartanalu).
germline mariyu somatic kanajaalaala madhya utparivartana retulo asamaanata soma kante germlinelo janyu samagrata yokka ekkuva praamukhyatanu pratibimbistumdi. utparivartana pounahpunyamlo vaividhyam anedi dna nashtam raetlaloo vyatyaasaalu ledhaa dna marammattu enjaimla yokka perigina sthaayila phalitamgaa dna marammattu prakriyaloo vyatyaasaala kaaranamgaa undavacchu.
april 2022loe chaalaa ksheeradaalu tama jeevitakaalam mugise samayaniki oke sankhyalo utparivartanaalanu kaligi untaayani nivedinchabadindi, kabatti saaruupya jeevitakaalam unnavaaru saaruupya somatic mutation retlanu kaligi untaaru mariyu takkuva/ekkuva jeevinchevaaru varusaga adhika/takkuva somatic utparivartanaalanu kaligi untaaru.
somatic hypermutation.
anukuula roganirodhaka pratispandanalo bhaagamgaa, pratirakshakaanni utpatti chese bii kanaalu utparivartana raetu saadhaarana utparivartana raetu kante chaalaa retlu ekkuvagaa untaayi. immunoglobulin janyuvula antigen-binding coding sequencelalo mutation raetu lymphoid vyavastha velupala unna kana rekhala kante 1,000,000 retlu ekkuvagaa untundi. anubandha paripakvatalo oka pradhana dasha, somatic hypermutation anedi bii kanaalu ekkuva antigen anubandhamtho pratiroedhakaalanu utpatti cheyadaaniki sahaayapadutundi.
vyaadhi.
saareeraka utparivartanalu oka jeevi yokka kanaalalo vayassu perige koddi mariyu prati round kana vibhajanatho kuudukoni perukupotayi; cancer abhivruddhilo saareeraka utparivartanaala paatra baga sthirapadindi, mariyu saareeraka utparivartanaala perukupovadam vruddhaapya jeevasaastramlo chikkukundi.
neuronal stem sels (mukhyamgaa neurogenesis samayamlo) mariyu post-mytotic neuronlalo utparivartanalu neuronla janyu vaividhyaaniki daariteestaayi-dheenini "somatic brain mosaism" anie pilustaaru. neuronlalo vayassu-sambandhita utparivartanalu perukupovadam anedi algimers vyaadhitho sahaa neurodegenerative vyaadhulatoe mudipadi undavacchu, conny anubandham niroopinchabadaledu. vayojanulalo kendra-naadii vyavastha kanaalalo ekkuva bhaagam post-mytotic, mariyu vayojana utparivartanalu oke neuronnu matrame prabhaavitam cheyavachu. utparivartanalu clonal vistaranaku daariteese cancerlo kakunda, haanikaramaina somatic utparivartanalu kana maranam dwara neurodegenerative vyaadhiki dohadam cheyavachu. anduvalla neuronlalo somatic mutation bhaaram yokka khachitamaina anchanaa anchanaa veyadam kashtam.
carcinogenesis loe paatra.
oka jeevi yokka kanamlo mutation sambhaviste, adhe jeevi lopala eee kanam yokka vaarasulandarilo aaa mutation untundi. saareeraka kanaala taraala taraala koddi konni utparivartanalu perukupovadam anedi saadhaarana kanam nundi cancer kanaaniki praanaantaka parivartana prakriyaloo bhaagam.
heterozygus laas-off-function utparivartanalu (janyuvu yokka oka manchi coppy mariyu oka utparivartana coppy) unna kanaalu manchi coppy aakasmikamgaa saareerakamgaa utparivartana chendhe varaku maarpu chendani kaapeetho saadhaaranamgaa panicheyavacchu. eee rakamaina mutation tarachugaa jeevulalo jarugutundi, conny retunu kolavadam kashtam. prajalu cancernu abhivruddhi chese retunu anchanaa veyadamlo eee retunu kolavadam mukhyam.

