IGENENOME YONKE IYAQHUBEKA
Ukwahluka kwesakhiwo kubantu baseTshayina kunye neempembelelo zabo kwi-phenotypes, izifo kunye nokulungelelaniswa kwabantu
Nanopore |PacBio |Ukulandelelana kwakhona kwegenome |Ubizo lokwahluka kolwakhiwo
Kolu phononongo, ulandelelwano lweNanopore PromethION lunikezelwe yiBiomarker Technologies.
Iimbalasane
Kolu phononongo, i-landscape iyonke yokwahluka kolwakhiwo (SVs) kwi-genome yomntu yatyhilwa ngoncedo lolandelelwano lokufunda ixesha elide kwi-Nanopore PromethION platfrom, eyenza nzulu ukuqonda kwe-SVs kwi-phenotypes, izifo kunye ne-evolution.
Uyilo loMfuniselo
Iisampulu: I-peripheral blood leukocytes ye-405 yabantu baseTshayina abangabalulekanga (i-206 yamadoda kunye ne-199 yabasetyhini) kunye ne-68 phenotypic kunye nemilinganiselo yekliniki.Phakathi kwabo bonke abantu, imimandla yookhokho babantu abayi-124 yayingamaphondo aseMantla, abo babengabantu abali-198 babengamaZantsi, abangama-53 babekuMzantsi-Ntshona kwaye abangama-30 babengaziwa.
Isicwangciso sokulandelelanisa: I-Genome yonke i-long-read sequencing (LRS) kunye ne-Nanopore 1D ifundeka kunye ne-PacBio HiFi efundwayo.
Iqonga lokulandelelana: I-Nanopore PromethION;I-PacBio Sequel II
Ukufowuna kokwahluka kwesakhiwo
Umzobo 1. Ukuhamba komsebenzi we-SV ukubiza kunye nokucoca
IziPhumo eziphambili
Ukufunyanwa kokwahluka kolwakhiwo kunye nokuqinisekiswa
I-Dateset ye-Nanopore: Iyonke i-20.7 Tb ecocekileyo efundwayo eyenziwe kwi-platform ye-PromethION yokulandelelana, ukuphumeza umyinge wedatha ye-51 Gb ngesampuli, malunga.17-ubunzulu.
Ulungelelwaniso lwe-genome yereferensi(GRCh38): Umndilili wokwenza iimephu wama-94.1% uphunyeziwe.Ixabiso lempazamo eliphakathi (12.6%) lalifana nophononongo lwangaphambili lokulinganisa (12.6%) (Umfanekiso 2b kunye ne-2c)
Ukwahluka kwesakhiwo (SV) ukufowuna: Abafowuni be-SV abafake isicelo kolu phando babandakanya i-Sniffles, i-NanoVar kunye ne-NanoSV.Ii-SV ezizithembayo eziphakamileyo zichazwe njenge-SVs ezichongiweyo ubuncinane ngabafowunayo ababini kunye nokuhlunga okugqithisiweyo kubunzulu, ubude kunye nommandla.
Umyinge we-18,489 (ukusuka kwi-15,439 ukuya kwi-22,505) ii-SV ezizithembayo eziphezulu zichongiwe kwisampuli nganye.(Umfanekiso 2d, 2e kunye no-2f)
Umzobo 2. Imbonakalo yomhlaba iyonke yee-SVs ezichongwe yiNanopore dataset
Ukuqinisekiswa kwePacBio: Ii-SV ezichongiweyo kwisampulu enye (HG002, umntwana) ziqinisekiswe yi-PacBio HiFi dataset.Ireyithi yokufumanisa ubuxoki ngokubanzi (i-FDR) yayiyi-3.2%, ebonisa ukuchongwa kwe-SV ethembekileyo ngokufundwa kweNanopore.
Ii-SV ezingafunekiyo kunye neempawu ze-genomic
Ii-SV ezingafunekiyo: Isethi ye-132,312 engafunekiyo i-SVs ifunyenwe ngokudibanisa i-SVs kuzo zonke iisampuli, ezibandakanya i-67,405 DELs, i-60,182 INSs, i-3,956 DUPs kunye ne-769 INVs.(Umfanekiso 3a)
Uthelekiso kunye neeseti zedatha ze-SV esele zikho: Le datha yathelekiswa neseti yedatha epapashiweyo ye-TGS okanye ye-NGS.Ngaphakathi kweeseti zedatha ezine xa kuthelekiswa, i-LRS15, ekwayiyo yodwa isethi yedatha evela kwiqonga lolandelelwano lokufunda ixesha elide(i-PacBio) ekwabelwana ngalo ngokugqithelana okukhulu nale datha.Ngaphezu koko, i-53.3% (70,471) yee-SVs kule datha yaxelwa okokuqala.Ngokujonga kudidi ngalunye lwe-SV, inani le-INSs ezifunyenweyo ezinedatha elandelelanisiweyo yokufunda ixesha elide lalilikhulu kakhulu kunezinye ezifundwayo ezimfutshane, nto leyo ebonisa ukuba ulandelelwano lokufunda ixesha elide lusebenza kakhulu ekubhaqweni kwe-INSs.(Umfanekiso 3b kunye no-3c)
Umzobo 3. Iipropati zee-SV ezingafunekiyo kuhlobo ngalunye lwe-SV
Iimpawu zeGenomic: Inani le-SVs lifunyenwe lihambelana kakhulu nobude bechromosome.Ukusasazwa kofuzo, ukuphindaphinda, i-DELs (eluhlaza), i-INS (eluhlaza okwesibhakabhaka), i-DUP (ephuzi) kunye ne-INV (i-orange) ziboniswe kwi-Circos diagram, apho ukwanda ngokubanzi kwe-SV kubonwe ekupheleni kweengalo ze-chromosome.(Umfanekiso 3d kunye no-3e)
Ubude be-SVs: Ubude be-INS kunye ne-DEL bufunyenwe bufutshane kakhulu kunezo ze-DUPs kunye ne-INVs, ezivumelana nezo zichongwe yi-PacBio HiFi dataset.Ubude bazo zonke ii-SVs ezichongiweyo zongezwe ukuya kwi-395.6 Mb, ethathe i-13.2% yegenome yomntu wonke.Ii-SVs zichaphazele i-23.0 Mb(malunga ne-0.8%) ye-genome ngomntu ngamnye kumndilili.(Umfanekiso 3f kunye no-3g)
Ukusebenza, i-phenotypical kunye neempembelelo zeklinikhi ze-SVs
Ukulahleka komsebenzi oqikelelweyo (pLoF) SVs: ii-pLoF SVs zachazwa njenge-SVs ezisebenzisana ne-CDS, apho iikhowudi ze-nucleotides zacinywa okanye ii-ORF zatshintshwa.Iyonke i-1,929 ye-pLoF SVs echaphazela i-CDS ye-1,681 yofuzo yachazwa.Ngaphakathi kwezo, iijini ezingama-38 ziqaqambise "i-immunoglobulin receptor binding" kuhlalutyo lwe-GO lokutyebisa.Ezi pLoF SVs ziye zachazelwa ngakumbi yi-GWAS, i-OMIM ne-COSMIC, ngokulandelelanayo.(Umfanekiso 4a kunye no-4b)
I-Phenotypically kunye neklinikhi echaphazelekayo ye-SVs: Inani le-SV kwi-dataset ye-nanopore iboniswe ukuba i-phenotypically kunye neklinikhi efanelekileyo.I-heterozygous DEL enqabileyo ye-19.3 kb, eyaziwa ngokubangela i-alpha-thalassemia, ichongiwe kubantu abathathu, abangasebenzi kakuhle i-Hemoglobin Subunit Alpha 1 kunye ne-2 (HBA1 kunye ne-HBA2).Enye i-DEL ye-27.4 kb kwi-gene coding ye-Hemoglobin Subunit Beta(HBB) ichongiwe komnye umntu.Le SV yaziwa ngokubangela i-hemoglobinopathies enzulu.(Umfanekiso 4c)
Umzobo 4. ii-pLoF SVs ezinxulumene neephenotypes kunye nezifo
I-DEL eqhelekileyo ye-2.4 kb yabonwa kwi-35 homozygous kunye ne-67 heterozygous carriers, ehlanganisa ummandla opheleleyo we-3rd exon ye-Growth Homone Receptor (GHR).Abathwali be-homozygous bafunyenwe bemfutshane kakhulu kune-heterzygous (p=0.033).(Umfanekiso 4d)
Ngaphaya koko, ezi SVs zaqhutyelwa kwizifundo zokuzivelela kwabantu phakathi kwamaqela amabini ommandla: uMntla noMzantsi China.Ii-SVs ezahluke kakhulu zifunyenwe zisasazwa kwi-Chr 1, 2, 3, 6,10,12,14 kunye ne-19, apho, ezona ziphezulu zazinxulunyaniswa nemimandla yokhuselo, njenge-IGH, MHC, njl.njl. Kusengqiqweni ukucinga ukuba Umahluko kwezi SVs unokuba ngenxa yokukhukhuleka kwemfuza kunye nokuvezwa kwexesha elide kwizinto ezohlukeneyo zabemi baseTshayina.
Isalathiso
Wu, Zhikun, et al."Ukwahluka kolwakhiwo kubemi baseTshayina kunye nefuthe labo kwi-phenotypes, izifo kunye nokulungelelaniswa kwabantu."i-bioRxiv(2021).
Iindaba neembalasane ijolise ekwabelaneni ngamatyala aphumeleleyo amva nje kunye neBiomarker Technologies, ukubamba impumelelo yesayensi enoveli kunye nobuchule obubalaseleyo obusetyenzisiweyo ngexesha lokufunda.
Ixesha lokuposa: Jan-06-2022