GUKURIKIRA GENOME YOSE
Imiterere ihindagurika mubaturage b'Abashinwa n'ingaruka zayo kuri phenotypes, indwara no kurwanya imihindagurikire y'abaturage
Nanopore |PacBio |Genome yose yongeye gukurikiranwa |Guhindura imiterere ihamagarwa
Muri ubu bushakashatsi, gahunda ya Nanopore PromethION yatanzwe na Biomarker Technologies.
Ingingo z'ingenzi
Muri ubu bushakashatsi, muri rusange imiterere yimiterere itandukanye (SVs) muri genome yabantu yerekanwe hifashishijwe urutonde rwasomwe igihe kirekire kuri platifomu ya Nanopore PromethION, ibyo bikaba byongera ubumenyi bwa SV muri fenotipi, indwara nubwihindurize.
Igishushanyo mbonera
Icyitegererezo: Amaraso ya leukocytes ya periferique yabantu 405 badafite aho bahurira nabashinwa (abagabo 206 nabagore 199) hamwe nibipimo 68 bya fenotipiki nubuvuzi.Mu bantu bose, uturere twa basekuruza twabantu 124 ni intara mumajyaruguru, abo bantu 198 bari amajyepfo, 53 bari SouthWest naho 30 ntibamenyekanye.
Ingamba zikurikirana: Genome yose isomwa igihe kirekire (LRS) hamwe na Nanopore 1D irasoma na PacBio HiFi irasoma.
Urubuga rukurikirana: Nanopore PromethION;Urutonde rwa PacBio II
Guhamagarira Guhindura Imiterere
Igicapo 1. Urujya n'uruza rwa SV guhamagara no kuyungurura
Ibyagezweho
Imiterere itandukanye kuvumbura no kwemeza
Amatariki ya Nanopore: Muri rusange 20.7 Tb isukuye yasomwe yakozwe kuri gahunda ikurikirana ya PromethION, igera ku kigereranyo cya 51 Gb kuri sample, hafi.Inshuro 17 zubujyakuzimu.
Guhuza genome (GRCh38): Ikigereranyo cyo gushushanya ikarita ya 94.1% cyagezweho.Ikigereranyo cyo kwibeshya (12,6%) cyari gisa nubushakashatsi bwibanze (12,6%) (Ishusho 2b na 2c)
Guhindura imiterere (SV) guhamagara: Abahamagaye SV bakoreshejwe murubu bushakashatsi barimo Sniffles, NanoVar na NanoSV.SV-yizeye cyane SVs zasobanuwe nka SV zagaragajwe byibuze nabahamagaye kandi zanyuze muyungurura uburebure, uburebure n'akarere.
Impuzandengo ya 18.489 (kuva kuri 15.439 kugeza 22,505) SVs yizeye cyane muri buri cyitegererezo.(Ishusho 2d, 2e na 2f)
Igishushanyo 2. Muri rusange imiterere ya SVs yagaragajwe na dataset ya Nanopore
Kwemeza na PacBio: SV zagaragaye muri sample imwe (HG002, umwana) byemejwe na dataset ya PacBio HiFi.Igipimo rusange cyo kuvumbura ibinyoma (FDR) cyari 3.2%, byerekana imiterere ya SV yizewe na Nanopore asoma.
SVs zirenze urugero nibiranga genomic
SVs zirenze urugero: Igice cya 132.312 SV zidakabije zabonetse muguhuza SV mubitegererezo byose, birimo DELs 67,405, INS 60,182, DUPs 3,956 na INV 769.(Isanamu 3a)
Ugereranije namakuru ya SV yabayeho: Iyi mibare yagereranijwe na TGS cyangwa imibare ya NGS yatangajwe.Muri dataseti enye ugereranije, LRS15, nayo niyo dataset yonyine kuva murwego rwo gusoma rurerure (PacBio) rwasangiye byinshi hamwe niyi mibare.Byongeye kandi, 53.3% (70,471) ya SV muri iyi dataset byavuzwe bwa mbere.Iyo urebye muri buri bwoko bwa SV, umubare wa INS zagaruwe hamwe na dataset zasomwe igihe kirekire zasomwe cyane kuruta izindi zisomwa mugufi, byerekana ko urutonde rumaze igihe kinini rusomwa neza cyane mugushakisha INSs.(Isanamu 3b na 3c)
Igishushanyo 3. Ibyiza bya SVs zidakabije kuri buri bwoko bwa SV
Ibiranga rusange: Umubare wa SV wasangaga uhujwe cyane nuburebure bwa chromosome.Ikwirakwizwa rya gen, gusubiramo, DELs (icyatsi), INS (ubururu), DUP (umuhondo) na INV (orange) byerekanwe ku gishushanyo cya Circos, aho ubwiyongere rusange muri SV bwagaragaye nyuma yintoki za chromosome.(Isanamu 3d na 3e)
Uburebure bwa SVs: Uburebure bwa INS na DELs wasangaga ari bugufi cyane ugereranije na DUPs na INVs, ibyo bikaba byemeranijweho na datBet ya PacBio HiFi.Uburebure bwa SVs zose zamenyekanye ziyongera kuri 395,6 Mb, zifata 13.2% ya genomuntu yose.SVs yibasiye 23.0 Mb (hafi 0.8%) ya genome kumuntu kugereranije.(Isanamu 3f na 3g)
Ingaruka zikorwa, fenotipiki nubuvuzi bwa SVs
SVs ziteganijwe gutakaza imikorere (pLoF) SVs: pLoF SVs zasobanuwe nka SVs zikorana na CDS, aho coding nucleotide zasibwe cyangwa ORF zahinduwe.Muri rusange, 1,929 pLoF SVs yibasira CDS ya gen 1.681.Muri ibyo, genes 38 zagaragaje "immunoglobulin reseptor binding" mu isesengura ryitunganyirizo rya GO.Izi SVs za pLoF zongeye gusobanurwa na GWAS, OMIM na COSMIC.(Isanamu 4a na 4b)
SVs zifitanye isano na clinique: Umubare wa SV muri dataset ya nanopore yerekanwe ko ari fenotipiki na clinique.DEL idasanzwe ya DEL ya 19.3 kb, izwiho gutera alfa-thalassemia, yagaragaye mubantu batatu, ikaba idakora neza ya Hemoglobin Subunit Alpha 1 na 2 (HBA1 na HBA2).Indi DEL ya 27.4 kb kuri gene code ya Hemoglobin Subunit Beta (HBB) yamenyekanye mubandi bantu.Iyi SV yari izwiho gutera hemoglobinopathies ikomeye.(Isanamu 4c)
Igicapo 4. SVo ya SV ifitanye isano na phenotypes n'indwara
DEL isanzwe ya 2,4 kb yagaragaye muri 35 bahuje ibitsina na 67 batwara ibinyabuzima, bikubiyemo akarere kuzuye ka exon ya 3 ya Growth Homone Receptor (GHR).Abatwara abaryamana bahuje igitsina wasangaga ari ngufi cyane ugereranije na heterzygous (p = 0.033).(Isanamu 4d)
Byongeye kandi, izi SV zatunganijwe kubushakashatsi bwihindagurika bwabaturage hagati y amatsinda abiri yo mu karere: Amajyaruguru n’Ubushinwa.SVs itandukanye cyane yabonetse yatanzwe kuri Chr 1, 2, 3, 6,10,12,14 na 19, muribwo, iyambere yari ifitanye isano nakarere k’ubudahangarwa, nka IGH, MHC, nibindi. gutandukana muri izi SVs birashobora guterwa no gutondekanya genetike hamwe nigihe kirekire cyo guhura nibintu bitandukanye kubantu batuye mubushinwa.
Reba
Wu, Zhikun, n'abandi.Ati: “Imiterere itandukanye mu baturage b'Abashinwa n'ingaruka zayo kuri fenotipi, indwara no kurwanya imihindagurikire y'abaturage.”bioRxiv(2021).
Amakuru n'ibikurubikuru igamije gusangira ibibazo byatsinzwe na Biomarker Technologies, gufata ibyagezweho mu buhanga hamwe nubuhanga bukomeye bwakoreshejwe mugihe cyo kwiga.
Igihe cyo kohereza: Mutarama-06-2022