The Human Genome Morero o senotse hore ~ 1-2% ea rona liphatsa tsa lefutso e etsa liprotheine tse sebetsang ha karolo ea 98-99% e setseng e ntse e le moferefere. Bafuputsi ba lekile ho senola liphiri tse mabapi le se tšoanang mme sengoloa sena se fana ka leseli kutloisisong ea rona ea karolo ea eona le litlamorao ho botho bophelo bo botle le mafu.
Ho tloha ka nako eo Human Genome Morero (HGP) o phethetsoe ka Mmesa 20031, ho ne ho nahanoa hore ka ho tseba tatellano eohle ea botho genome e nang le li-base pairs tse limilione tse likete tse 3 kapa 'mangolo a mabeli', liphatsa tsa lefutso e tla ba buka e bulehileng e sebelisang eo bafuputsi ba tla khona ho totobatsa hantle hore na sebopuoa se rarahaneng joalo ka botho Ho ba mesebetsi eo qetellong e tla lebisa ho fumaneng maemo a rona a mefuta e fapaneng ea mafu, ho matlafatsa kutloisiso ea rona ea hore na ke hobane'ng ha lefu le hlaha le ho fumana pheko bakeng sa 'ona. Leha ho le joalo, boemo bo ile ba tsieleha haholo ha bo-rasaense ba khona ho hlalosa feela karolo ea eona (feela ~ 1-2%) e etsang liprotheine tse sebetsang tse etsang qeto ea ho ba teng ha rona ka phenotypic. Karolo ea 1-2% ea DNA ho etsa liprotheine tse sebetsang e latela thuto e bohareng ea biology ea limolek'hule e bolelang hore DNA e kopitsoa pele ho etsa RNA, haholo-holo mRNA ka mokhoa o bitsoang transcription e lateloang ke tlhahiso ea protheine ka mRNA ka phetolelo. Ka puo ea setsebi sa baeloji ea limolek'hule, sena 1-2% ea botho liphatsa tsa lefutso likhoutu bakeng sa liprotheine tse sebetsang. 98-99% e setseng e bitsoa 'junk DNA' kapa 'lefifi taba' e sa hlahiseng leha e le efe ea liprotheine tse sebetsang tse boletsoeng ka holimo 'me e tsamaisoa e le' thoto' nako le nako botho ho tsoaloa. E le hore u utloisise karolo ea ba setseng 98-99% ea liphatsa tsa lefutso, ENCODE ( ENCYclopedia Of DNA Elements) morero2 e ile ea thakholoa ka Loetse 2003 ke National Human Genome Setsi sa Lipatlisiso (NHGRI).
Liphuputso tsa morero oa ENCODE li senotse hore boholo ba lefifi taba'' e na le tatellano ea DNA e sa ngolisoeng e sebetsang e le likarolo tsa bohlokoa tsa taolo ka ho bulela le ho tima liphatsa tsa lefutso mefuteng e fapaneng ea lisele le libakeng tse fapaneng ka nako. Liketso tsa sebaka le tsa nakoana tsa tatellano ena ea taolo li ntse li sa hlaka ka ho feletseng, kaha tse ling tsa tsena (likarolo tsa taolo) li hōle haholo le lefutso leo li sebetsang ho lona ha maemong a mang li ka 'na tsa atamelana.
Sebopeho sa tse ling tsa libaka tsa botho liphatsa tsa lefutso e ne e tsejoa le pele ho qala ho Human Genome Morero ho hoo ~ 8% ea botho liphatsa tsa lefutso e tsoa ho kokoana-hloko genomes e kentsoeng ho DNA ea rona joalo ka botho Endogenous retroviruses (HERVs)3. Li-HERV tsena li kentse letsoho ho faneng ka tšireletso ea tlhaho ho batho ka ho sebetsa e le likarolo tsa taolo bakeng sa liphatsa tsa lefutso tse laolang tšebetso ea 'mele ea ho itšireletsa mafung. Bohlokoa ba ts'ebetso ea 8% ena bo netefalitsoe ke liphuputso tsa projeke ea ENCODE e khothalelitseng hore boholo ba 'lefifi. taba e sebetsa joalo ka likarolo tsa taolo.
Ntle le liphuputso tsa projeke ea ENCODE, ho na le lintlha tse ngata tsa lipatlisiso tse fumanehang lilemong tse mashome a mabeli tse fetileng tse fanang ka maikutlo a karolo ea taolo le nts'etsopele ea 'lefifi. taba'. Ho sebelisa Genome-wide association studies (GWAS), ho khethiloe hore boholo ba libaka tse sa ngolisoeng tsa DNA li amahanngoa le maloetse le mekhoa e tloaelehileng.4 le mefuta e fapaneng ea libaka tsena e sebetsa ho laola ho qala le ho teba ha palo e kholo ea mafu a rarahaneng a kang kankere, lefu la pelo, mathata a boko, botenya, har'a tse ling tse ngata.5,6. Liphuputso tsa GWAS li boetse li senoletse hore boholo ba tatellano ena ea DNA e sa ngolisoeng ka har'a genome e ngoloa (e fetoleloa ho RNA ho tloha DNA empa e sa fetoleloa) ho li-RNA tse sa ngolisoeng 'me ho senyeha ha melao ea tsona ho lebisa ho mafu a fapaneng a bakang liphello.7. Sena se fana ka maikutlo a bokhoni ba li-RNA tse sa ngoliseng likhoutu ho bapala karolo ea taolo ho nts'etsopele ea lefu lena8.
Ho feta moo, tse ling tsa litaba tse lefifi li sala e le DNA e sa ngolisoeng 'me e sebetsa ka mokhoa oa taolo e le lintlafatso. Joalokaha lentsoe le fana ka maikutlo, lisebelisoa tsena tse matlafatsang li sebetsa ka ho ntlafatsa (ho eketsa) polelo ea liprotheine tse itseng ka seleng. Sena se bonts'itsoe phuputsong ea morao-rao moo litlamorao tsa sebaka se sa ngolisoeng sa DNA se etsa hore bakuli ba hlaseloe ke mafu a rarahaneng a autoimmune le allergic joalo ka lefu la ho ruruha ha mala.9,10, ka tsela eo e lebisang ho khethoeng ha sepheo se secha sa phekolo bakeng sa phekolo ea mafu a ho ruruha. Lintho tse matlafatsang 'tabeng e lefifi' le tsona li kentse letsoho kholong ea boko moo liphuputso tsa litoeba li bonts'itseng hore ho hlakoloa ha libaka tsena ho baka ho se tloaelehe kholisong ea boko.11,12. Lithuto tsena li ka re thusa ho utloisisa hamolemo mafu a rarahaneng a methapo a kang Alzheimer's le Parkinson's. 'Lintho tse lefifi' li boetse li bontšitsoe hore li na le karolo ho nts'etsopele ea kankere ea mali13 tse kang chronic myelocytic leukemia (CML) le chronic lymphocytic leukemia (CLL).
Kahoo, 'taba e lefifi' e emela karolo ea bohlokoa ea botho liphatsa tsa lefutso ho feta kamoo ho neng ho nahanoa ka teng mme e na le litšusumetso ka kotloloho botho bophelo bo botle ka ho bapala karolo ea taolo ho nts'etsopele le ho qala ha botho mafu joalokaha ho hlalositsoe ka holimo.
Na hoo ho bolela hore 'taba e lefifi' kaofela e ngotsoe ho li-RNA tse sa ngolisoeng kapa li bapala karolo e matlafatsang joalo ka DNA e sa ngolleng likhoutu ka ho sebetsa e le likarolo tsa taolo tse amanang le maemo a teng, ho qala le ho fapana ha mafu a fapaneng a bakang. batho? Liphuputso tse entsoeng ho fihlela joale li bonts'a ts'ebetso e matla ea lipatlisiso tse ts'oanang le tse ngata lilemong tse tlang li tla re thusa ho hlalosa hantle mosebetsi oa 'mabaka a lefifi', a tla lebisa ho khethoeng ha lipakane tse ncha ka tšepo ea ho fumana pheko. mafu a fokolisang a hlaselang moloko wa batho.
***
References:
1. "Pheletso ea Morero oa Genome ea Batho: Lipotso Tse Botsoang Hangata". Batho ba Sechaba Genome Setsi sa Lipatlisiso (NHGRI). E fumaneha inthaneteng ho https://www.genome.gov/human-genome-project/Completion-FAQ E fihletsoe ka 17 May2020.
2. Smith D., 2017. The mysterious 98%: Bo-rasaense ba sheba ho khantša leseli ho 'lefifi la genome'. E fumaneha inthaneteng ho https://phys.org/news/2017-02-mysterious-scientists-dark-genome.html E fihletsoe ka 17 May 2020.
3. Soni R., 2020. Batho le Livaerase: Nalane e Khutšoanyane ea Kamano ea Bona e Ratang le Litlamorao ho COVID-19. Scientific European Posted 08 May 2020. E fumaneha Inthaneteng ho https://www.scientificeuropean.co.uk/humans-and-viruses-a-brief-history-of-their-complex-relationship-and-implications-for-COVID-19 E fihletsoe ka 18 May 2020.
4. Maurano MT, Humbert R, Rynes E, et al. Sebaka se hlophisitsoeng sa phetoho e tloaelehileng e amanang le lefu ho DNA ea taolo. Saense. 2012 Sep 7;337(6099):1190-5. DOI: https://doi.org/10.1126/science.1222794
5. Lethathamo la Lithuto tse Phatlalalitsoeng tsa Genome-Wide Association. http://www.genome.gov/gwastudies.
6. Hindorff LA, Sethupathy P, et al 2009. Ho ka etsahala hore ebe etiologic le ts'ebetso ea ts'ebetso ea genome-wide association loci bakeng sa maloetse le litšobotsi tsa batho. Proc Natl Acad Sci US A. 2009, 106: 9362-9367. DOI: https://doi.org/10.1073/pnas.0903103106
7. St. Laurent G, Vyatkin Y, le Kapranov P. Lefifi la RNA le khantša papali ea lithuto tsa mekhatlo ea genome-wide. BMC Med 12, 97 (2014). DOI: https://doi.org/10.1186/1741-7015-12-97
8. Martin L, Chang HY. Ho senola karolo ea genomic "dark matter" ho mafu a batho. J Clin Tsetela. 2012;122 (5): 1589-1595. https://doi.org/10.1172/JCI60020
9. The Babraham Institute 2020. Ho sibolla hore na libaka tsa 'dark matter' tsa genome li ama mafu a ho ruruha joang. E ngotsoe 13 May, 2020. E fumaneha Inthaneteng ho https://www.babraham.ac.uk/news/2020/05/uncovering-how-dark-matter-regions-genome-affect-inflammatory-diseases E fihletsoe ka 14 May 2020.
10. Nasrallah, R., Imianowski, CJ, Bossini-Castillo, L. et al. 2020. Distal enhancer at risk locus 11q13.5 e khothalletsa khatello ea colitis ke Treg cells. Tlhaho (2020). DOI: https://doi.org/10.1038/s41586-020-2296-7
11. Dickel, DE et al. 2018. Ultra conserved enhancers e hlokahala bakeng sa tsoelo-pele e tloaelehileng. Cell 172, Khatiso ea 3, P491-499.E15, Pherekhong 25, 2018. DOI: https://doi.org/10.1016/j.cell.2017.12.017
12. 'Ntho e lefifi' DNA e susumetsa kholo ea boko DOI: https://doi.org/10.1038/d41586-018-00920-x
13. Litaba tse lefifi: Ho khetholla mofetše oa mali o poteletseng ka ho sebelisa DNA DOI e lefifi ka ho fetesisa: https://doi.org/10.1371/journal.pcbi.1007332
***