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Watter spesies het hul genome in volgorde laat volg?

Watter spesies het hul genome in volgorde laat volg?



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Die menslike genoomprojek het sy eerste volledige genoom bykans tien jaar gelede vrygestel. Sedertdien is baie spesies ook in volgorde geplaas.

Ek probeer 'n lys vind van voltooide (en moontlik lopende/geïnisieerde) projekte om ander spesies te volg, asook 'n paar basiese opsommingsdata, soos die aantal gene (verdeel tussen die geslagschromosome en outosome), lengte van DNA, aantal chromosome, ens .

Dit is vir 'n aanbieding wat ek by 'n konferensie gee en sal 'n goeie toevoeging tot my praatjie wees.


Die GOLD -databasis (Genomes Online DB) bevat data oor die volgorde -status, en ook 'n paar statistieke (aantal chromosome, genoomgrootte) - maar hierdie ekstra data is nie vir alle spesies beskikbaar nie.


Daar is verskeie lyste op Wikipedia, byvoorbeeld vir plante, bakterieë en eukariote.


Die Genome 10K-projek, in hul woorde "het ten doel om 'n genomiese dieretuin saam te stel - 'n versameling DNS-volgordes wat die genome van 10 000 gewerwelde spesies verteenwoordig, ongeveer een vir elke gewerwelde genus." Hier is hul spesie lys.


By NCBI vind u 'n tabel met genoominligting per organisme.

Vir elke organisme kan jy die Koninkryk, groep en subgroep waartoe dit behoort, die grootte in Megabasisse, die aantal chromosome, organelle en plasmiede (indien teenwoordig) en die aantal samestellings vind.


Heel-genoom-data wys na vier spesies kameelperde

Ruth Williams
6 Mei 2021

BO: Kameelperd reticulata in Samburu National Park, Kenia
GIRAFFE BEWARINGSSTIGTING, JULIAN FENNESSY

Navorsers voer die mees gedetailleerde genomiese volgorde -analise tot dusver van die hoogste landdier ter wêreld aan, en voer aan dat vier verskillende kameelperdesoorte bestaan. Maar hul verslag, wat gister (5 Mei) in Huidige biologie, blyk nie die langdurige debat onder kameelperdkenners oor presiese spesiegetalle by te lê nie, met sommige wat steeds aanvoer daar is waarskynlik meer spesies en ander minder.

"Dit is werklik moderne genetiese data [en] 'n geweldige bydrae tot die wetenskap," sê die evolusionêre genetikus Rasmus Heller van die Universiteit van Kopenhagen wat nie by die navorsing betrokke was nie. "Dit is regtig lekker dat ons uiteindelik volledige genoomdata op hierdie skaal vir kameelperde het," voeg hy by en merk op dat dit nie maklik is om baie genome te hê wat soveel kameelperde bevolkings verteenwoordig nie. Oor of hy dink die data bevestig die bestaan ​​van vier en slegs vier spesies, sê hy, "dit was 'n soort van 'n omstrede kwessie vir 'n aantal jare en . . . Ek verkies om 'n bietjie agnosties te bly. . . . Ek weet regtig nie, om eerlik te wees. ”

Sedert mense die spesies begin klassifiseer het, is die ikoniese kameelperd, wat op die savanne van Afrika ronddwaal en aan bome ronddwaal en bo alle ander diere uitstyg, as 'n enkele spesie beskou. Met die koms van genetiese volgorde is voorstelle van ses, agt, vier en drie spesies kameelperde, met verskillende subspesies, voorgestel.

En die debat is "verbasend warm", sê Heller. "Dit is 'n probleem dat die lewe deurmekaar en moeilik is om te duiwel, en mense met 'n brein wat dinge kompulsief in duiwegate steek," voeg die natuurlewe -bioloog Derek Lee van die Penn State University by wat nie aan die studie deelgeneem het nie.

"[Ons wou] hierdie probleem eens en vir altyd aanpak," sê die evolusionêre genetikus Axel Janke van die Senckenberg Biodiversity and Climate Research Center in Duitsland.

Janke se span het 'n verwysingsgenoom geskep deur 'n nuut-opeenvolging van 'n nuut verworwe kameelperd-DNA-monster te volg, en dit gebruik om nog 50 hele genome te verkry wat verkry is uit heropvolging van bestaande kameelperdmonsters van hoë gehalte en twee in die algemeen beskikbare kameelperde. Drie en veertig van die monsters kom van wilde populasies op 17 plekke regoor die Afrika-kontinent, wat deur lede van die Giraffe Conservation Foundation (GCF) versamel is. Die oorblywende agt individue kom uit drie Europese dieretuine. Die monsters verteenwoordig lede van alle vermeende spesies of subspesies van die soogdier.

Vergelykende volgorde-ontledings, wat byna 200 000 enkelnukleotied-polimorfismes in die diere se genome ondersoek het, het Janke se vorige bevinding bevestig dat die rye in vier afsonderlike groepe of spesies groepeer. Die vorige studie was gebaseer op slegs sewe genomiese lokusse tesame met mitochondriale volgordes. Die hele-genoom-analise van die span het verder gesuggereer dat die vier afstammelinge afsonderlik ontwikkel het sonder dat daar 'n beduidende bewys van verbastering was. Volgens die span is die spesies: Giraffa camelopardalis (insluitend die subspesie G. c. antiquorum, G. c. camelopardalis, en G. c. peralta) G. tippelskirchi (insluitend die subspesie G. t. tippelskirchi en G. t. thornicrofti) G. kameelperd (insluitend die subspesie G. g. angolensis en G. g. kameelperd) en G. reticulata.

Alhoewel hibridisering tussen hierdie spesies in gevangenskap kan plaasvind, vandaar die vorige argument vir 'n enkele kameelperd, "sien ons geen tekens van verbastering in die genome nie, en deur afleiding sê ons dat dit nie in die natuur voorkom nie," sê Janke , en dit ondersteun die biologiese definisie van aparte spesies, sê hy.

Sien "Hybride diere is nie die verkeerde dinge van die natuur nie"

Evolusionêre bioloog Alexandre Hassanin van Sorbonne Universiteit, wie se vorige ontleding vir die bestaan ​​van slegs drie spesies aangevoer het, stem nie saam nie. Hy skryf in 'n e-pos aan Die wetenskaplike dat hibridisasie wel tussen plaasvind G. reticulata en G. camelopardalis, wat hulle lede van dieselfde spesie maak. Die huidige artikel, sê hy, "is beperk in omvang omdat die skrywers kies om slegs 'n enkele wilde populasie van die subspesie in te sluit. reticulata in hul genomiese ontledings. ” As hulle “bevolkings van reticulata in die westelike en noordelike dele van die verspreiding daarvan, is ek redelik seker dat die gevolgtrekkings anders sou wees, ”voeg hy by.

Daarteenoor beweer die molekulêre bioloog Douglas Cavener van die Penn State University dat daar meer as net vier spesies kan wees. Hy sê omdat die span nie die presiese liggings van die diere wat gemonster is bekend maak nie, is dit moontlik dat sommige lede van dieselfde familie kan wees en dus geneties baie soortgelyk aan mekaar is. As dit die geval is, sê hy, kan die natuurlike bevolkings eintlik meer divers wees, met meer spesies en subspesies as wat hierdie studie aandui.

Janke skryf in 'n opvolg-e-pos aan Die wetenskaplike, "Die monsters is van pylbiopsies wat deur GCF oor 'n paar dae geneem is, dink ek. Natuurlik kan 'n mens nooit uitsluit dat verwante individue betrek word nie, maar ek is baie vol vertroue deur te weet hoe professioneel die GCF-span eerstehands werk dat hulle hul bes gedoen het om steekproefneming van verwante individue te vermy."

Sien "Genoom onthul leidrade aan kameelperde se 'skitterend vreemde' liggaamsvorm"

So, hoekom maak dit selfs saak om die presiese aantal kameelperdspesies te ken?

'Of ons nou daarvan hou of nie, die spesie is steeds die basiese geldeenheid. . . om biodiversiteit te meet, ”sê Heller, en“ die manier waarop bewarings aandag en hulpbronne toegeken word, is gebaseer op spesie -afbakening. . . . Dit is die spesie -eenheid wat ons graag wil beskerm. ”

As daar vier spesies kameelperde in plaas van een is, verduidelik Heller, "het hulle elkeen hul eie status", wat die bewaringspogings kan versterk.

Uiteindelik, sê Cavener, is dit jammer dat daar soveel kontroversie was oor hierdie kwessie van spesies, want as ek daaroor kom, "dink ek, het almal dieselfde belangstelling, en dit is die bewaring van kameelperde."


Wetenskaplikes rangskik genome van 240 diere om evolusie op DNS -vlak te verstaan

'N Multidissiplinêre span wetenskaplikes onder leiding van Elinor Karlsson, PhD, medeprofessor in molekulêre medisyne in die program in bioinformatika en berekeningsbiologie, het biodiversiteit op genetiese vlak vasgelê. Deur opeenvolging van die genoom van 240 soogdierspesies, waarvan 122 nog nooit in volgorde geplaas is nie, het navorsers 'n korrelasie tussen streke van verminderde genetiese diversiteit in spesies met 'n hoër risiko-uitsterwing geïdentifiseer. Verdere gebruik van hierdie vergelykende genome sal wetenskaplikes in staat stel om stukke DNA te identifiseer wat miljoene jare by soogdiere onveranderd (of bewaar) gebly het, wat tot nuwe insigte in menslike gesondheid, siektes en biodiversiteit gelei het.

"Wat ons kon doen deur die volgorde van hierdie genome te volg, is om biodiversiteit op genetiese vlak vas te lê," het dr. Karlsson gesê. "Deur hierdie data te neem, kan ons soogdiergenome oor spesies heen ontleed om te sien wat oor miljoene jare verander of nie verander nie op interessante maniere oor al hierdie genome. Dit sluit areas van die genoom in waar veranderinge waarskynlik tot siekte of siekte sal lei.”

Die data, gepubliseer in Natuur, is reeds gebruik om die siekte en siektes verder te verstaan. Vroeër vanjaar was Karlsson een van die skrywers wat die werk in 'n Verrigtinge van die National Academy of Sciences studie wat spesies geïdentifiseer het wat veral SARS-CoV-2 oordraagbaar kan wees vir mens-tot-dier oordrag.

Om 'n uiteenlopende en wye verskeidenheid spesies te vang om 'n genomiese datastel te genereer wat nuttig was, het Karlsson ten minste een spesie uit elke eutherse familie ingesluit. Onder die spesies wat geselekteer is, is nege wat die enigste lede van hul familie is en sewe wat ernstig bedreig is, insluitend die Mexikaanse brulaap, hirola, Russiese saiga, sosiale tuco-tuco, indri, noordelike witrenoster en swartrenoster. In totaal word 80 persent van soogdierfamilies in Karlsson se vergelykende analise verteenwoordig.

'Baie van hierdie diere kan nie in dieretuine gevind word nie,' verduidelik Karlsson. 'Ons kon slegs DNA -monsters kry deur die veld in te gaan en hierdie spesies in hul eie habitat te vind. Vir spesies wat op afgeleë plekke woon, soos die reënwoud of die diep oseaan, is dit 'n groot uitdaging om 'n DNS -monster terug te bring na die laboratorium wat van 'n kwaliteit was wat gevolg kan word. "

Sodra Karlsson en haar span die rye gehad het, moes hulle die data ontleed. Om dit te kan doen, moes die verskillende genome korrek ingelyn word sodat ooreenstemmende genetiese streke akkuraat bestudeer word. Dit het nege maande se wolkrekenaarkunde vergelyk om 240 genome, insluitend mense, basies vir basies te vergelyk en dit presies op te stel, om tot 'n enkele basisresolusie te kom. 'Berekenend is dit 'n groot oplewing', het Karlsson gesê.

Sodra al die data verwerk is, kon wetenskaplikes 3,1 persent van die soogdiergenoom isoleer wat byna identies was tussen al 240 spesies.

'Wat dit beteken', sê Karlsson, 'is dat hierdie DNA -rye onveranderd was sedert die tyd dat al hierdie spesies 'n gemeenskaplike voorouer gedeel het - miljoene en miljoene jare terug. Dit is meer as wat ons sou verwag van ewekansige mutasies. Dit sou daarop dui dat hierdie dele van DNA van kritieke belang is vir die lewe, en dat diere met mutasies in hierdie gebiede geneig was om nie lank genoeg te oorleef om voort te plant nie. "

Een van die aanvanklike vrae wat Karlsson kon ondersoek, was hoeveel diversiteit in die genoom van 'n gegewe spesie bestaan.

"As ons op soek is na vroeë seine dat 'n bevolking bedreig kan word, en kan baat vind by ingryping van bewaringsgroepe, kan ons dit in die genetiese data vind," het Karlsson gesê. 'Spesies met minder biodiversiteit het waarskynlik minder genetiese verskille tussen die DNA wat van ma geërf is en die DNA wat van vader af is. Hierdie spesies kan geïdentifiseer word met behulp van genetiese data voordat die bevolkingsgetalle vinnig daal en geprioritiseer word vir diepgaande studie. ”

Terwyl soek na areas van ooreenkomste tussen spesies kan lei tot insigte in menslike gesondheid en siekte, Karlsson is ook geïntrigeerd deur genetiese verskille tussen spesies. "As jy dink aan al die dinge wat ander spesies kan doen wat mense nie kan doen nie, soos winterslaap," het Karlsson gesê. 'Elke jaar hou diere wat in die winterslaap is, kalorieë op, word insulienweerstandig en slaap. Dan spring hulle net terug. Mense kan dit nie doen nie. Dit sou rampspoedig wees. Wat is die gene wat dit beheer? Wat beteken dit en hoe hou dit verband met die werking van die menslike genoom? Dit is die uiteindelike vraag.”


Wetenskaplikes rangskik genome van 131 plasentale soogdierspesies

In 'n studie wat implikasies het om medisyne en biodiversiteitsbewaring te bevorder, het 'n groot internasionale konsortium van navorsers betrokke by die Zoonomia-projek die genome van 131 spesies plasentale soogdiere se volgorde en ontleed, wat die wêreldwye totaal op 240 te staan ​​bring.

Die Zoonomia -projek bring die fraksie eutherse soogdierfamilies wat deur ten minste een vergadering verteenwoordig word, op 83%. Hierdie beeld wys die bruinkeelluiaard (Bradypus variegatus) in die Cahuita Nasionale Park, Costa Rica. Beeldkrediet: Christian Mehlführer / CC BY 2.5.

Die genomika-revolusie maak vooruitgang nie net in mediese navorsing moontlik nie, maar ook in basiese biologie en in die bewaring van biodiversiteit, waar genomiese hulpmiddels gehelp het om stropers vas te trek en om bedreigde bevolkings te beskerm.

Ons het egter slegs 'n beperkte vermoë om te voorspel watter genomiese variante lei tot veranderinge in organisme-vlak fenotipes, soos verhoogde siekte risiko — 'n taak wat, in mense, bemoeilik word deur die blote grootte van die genoom.

Vergelykende genomika kan hierdie uitdaging die hoof bied deur die identifisering van nukleotiedposisies wat onveranderd gebly het gedurende miljoene jare se evolusie, en die soeke na siektes wat variëteite veroorsaak, gefokus word.

In 2011 het die 29 soogdiere -projek genetiese gebiede van evolusionêre beperking geïdentifiseer wat in totaal 4,2% van die genoom uitmaak, deur die behoud van volgorde by mense plus 28 ander soogdiere te meet.

Hierdie streke het geblyk meer verryk te wees vir die oorerflikheid van komplekse siektes as enige ander funksionele merk, insluitend koderingstatus.

Deur die aantal spesies uit te brei en 'n belyning te maak wat onafhanklik is van enige enkele verwysingsgenoom, is die Zoonomia -projek, wat vroeër die 200 Mammals Project genoem is, ontwerp om evolusionêre beperkings in die eutherse afstamming op te spoor met 'n groter resolusie, en verskaf genomiese hulpbronne vir meer as 130 voorheen ongekarakteriseerde spesies.

"Die vergelyking van die genome van die 240 soogdiere sal genetici help om die mutasies te identifiseer wat tot menslike siektes lei," het professor Kerstin Lindblad-Toh, 'n navorser aan die Uppsala Universiteit, SciLifeLab en die Broad Institute of MIT en Harvard, gesê.

Die Zoonomia-wetenskaplikes het genetiese innovasies geïdentifiseer wat blykbaar sekere diere teen siektes soos kanker en diabetes beskerm.

Hulle het ook genomiese elemente vasgestel wat onveranderd gebly het gedurende miljoene jare van evolusie, wat voorspel waar mutasies waarskynlik met die risiko van siektes verband hou, en wat nuwe weë van terapeutiese ontwikkeling kan onthul.

'Voor die mikroskoop kon ons nie sien wat binne -in 'n sel aangaan nie,' sê dr. Oliver Ryder, kleberg, direkteur van bewaringsgenetika aan die San Diego Zoo Institute for Conservation Research.

'Nou kyk ons ​​na die lewe vanuit 'n heeltemal nuwe perspektief. DNS dra instruksies, en nou kan ons dit lees.”

Filogenetiese boom van die soogdierfamilies in die belyning van die Zoonomia-projek, insluitend beide nuwe byeenkomste en alle ander soogdiergenome van hoë gehalte wat in die openbaar in GenBank beskikbaar was toe die span begin het. Bestaande taksonomiese klassifikasies herken 'n totaal van 127 bestaande families van eutherse soogdiere, insluitend 43 gesinne wat nie voorheen in GenBank verteenwoordig was nie (rooi bokse) en 41 gesinne met bykomende verteenwoordigende genoomversamelings (pienk bokse). Van die oorblywende gesinne het 21 GenBank -genoomvergaderings gehad, maar geen Zoonomia -projek (grys bokse) en 22 het geen verteenwoordigende genome -samestelling (wit bokse) nie. Hakies dui die aantal spesies met genoomsamestellings in 'n gegewe familie aan. Beeldkrediet: Genereux et al., doi: 10.1038/s41586-020-2876-6.

Benewens die begrip van die menslike genoom, kan alle nuwe genome van die plasentale soogdiere saam gebruik word om te bestudeer hoe spesifieke spesies by verskillende omgewings aanpas.

Sommige otters het byvoorbeeld 'n dik, waterbestande pels, en sommige muise, maar nie almal nie, het by hibernasie aangepas. Hierdie diere-eienskappe kan ons help om menslike eienskappe soos metaboliese siektes te verstaan.

Met klimaatsverandering en meer dierehabitatte wat deur menslike aktiwiteite geraak word, word dit al hoe belangriker om bedreigde spesies te verdedig.

In die nuwe studie het diere op die IUCN-rooilys van bedreigde spesies minder variasie in hul genoom gehad, wat ooreenstem met hul bedreigde status.

"Ons hoop dat ons uitgebreide datastel, wat vir alle wetenskaplikes ter wêreld beskikbaar is, gebruik sal word om siektegenetika en die beskerming van biodiversiteit te verstaan," het professor Lindblad-Toh gesê.

"Genoomvolgorde vir bedreigde spesies kan help om die risiko van uitwissing van 'n spesie te identifiseer en pogings tot bewaring te bestuur," het dr. Megan Owen, korporatiewe direkteur van natuurbewaringskunde by San Diego Zoo Global, gesê.

“Hulle gee ook aan wildbeamptes gereedskap om stropers en wildsmokkelaars vas te trek.”

"Een van die opwindendste dinge van die Zoonomia-projek is dat baie van ons kernvrae toeganklik is vir mense binne sowel as buite die wetenskap," sê dr. Diane Genereux, 'n navorsingswetenskaplike in die Vertebrate Genomics Group by die Broad Institute of MIT en Harvard.

"Deur wetenskaplike projekte te ontwerp wat vir almal toeganklik is, kan ons voordele vir die openbare, menslike en omgewingsgesondheid verseker."

Die span se resultate is in die uitgawe van 12 November 2020 van die joernaal gepubliseer Natuur.


Hoe wetenskaplikes besluit watter diergenome om te volgorde

Wat het paddas, orangoetangs en bokke in Afrika in gemeen? Genetici het diep, diep binne -in hul gene gekyk: hierdie spesies het hul hele genome op volgorde laat volg.

Verwante inhoud

U het moontlik gehoor van die moontlikheid om u eie hele genoom in volgorde te kry. 'n Paar jaar gelede het die prys van volgordebepaling van 'n menslike genoom tot $1 000 gedaal. Dit is nie sakgeld nie, maar dit is ook nie die $2,7 miljard wat dit gekos het om die eerste menslike genoom te volg nie. Met diere is dit egter meer ingewikkeld. Aangesien geen ander van die spesies ooit opeenvolg is nie, is dit moeiliker om die genoom sonder enige verwysing saam te stel.

Die rondewurm C. elegans het die eerste dier geword om sy genoom op te volg, en#160 in 1998. Sedertdien het   beter tegnologie vir genoomvolgorde wetenskaplikes in staat gestel om aan te beweeg na aansienlik meer ingewikkelde organismes en die volgorde baie vinniger en doeltreffender te doen. &# 160

Maar dit is steeds onwaarskynlik dat wetenskaplikes ooit die genoom van elke dier sal volg. Hulle moet kies en keur. So, waar om te begin?

Daar’s niemand kriteria waarop hierdie besluit geneem word. Soms is dit nodig om bewus te maak van die spesie en die potensiële voordeel daarvan vir die mensdom: dit was die rede waarom navorsers van die Nasionale Universiteit van Singapoer vroeër vanjaar aansoek gedoen het om finansiering om die genoom van die tempelput -adder te volg, skryf Samantha Boh vir die Singapore Times. Die adder is die enigste slangspesie waarvan bekend is dat dit 'n gifstof genaamd waglerin produseer, en sy skryf 'n neuromuskulêre remmer wat volgens wetenskaplikes ontwikkel kan word tot 'n spierverslappende middel. ”

Behalwe die moontlike mediese voordele van genoomvolgorde, is die praktyk belangrik vir basiese wetenskaplike en historiese begrip van die wêreld. Die historiese voetspore van die aanpassingsgebeurtenisse wat hulle gelei het tot waar hulle vandag is, is in die genome van lewende spesies gevestig, het Stephen O ’Brien, hoof van die Laboratory of Genomic Diversity, op 'n konferensie gesê.

Die bestudering van die huidige genome van diere kan wetenskaplikes vertel oor hul verlede as 'n spesie–en die geskiedenis van die omgewings waar hulle’ve geleef het en die ander spesies wat saam met hulle gewoon het. Byvoorbeeld, die genome van mak diere kan help om die verlede van die mensdom te verduidelik. Beide mense en diere, soos koeie en varke, is verander (en word steeds verander) toe 'n deel van die mensdom gevestig is en begin boer het. Om te bestudeer hoe hulle ontwikkel het toe hulle mak geword het, help genetici om die faktore in antieke menslike evolusie te verstaan, en dit kan help om te verduidelik wanneer presies die diere mak gemaak is.

Die genome van hierdie huisdiere het die mensdom ook baie te bied. “Akkurate verwysingsgenome is belangrik vir die begrip van 'n organisme se biologie, om te leer oor die genetiese oorsake van gesondheid en siektes en, by diere, vir die neem van teelbesluite,”  volgens a National Human Genome Research Institute pers vrylating.  

Soms help die volgorde van 'n dier se genoom wetenskaplikes om skerp te bly. Kanadese navorsers wat normaalweg op die menslike genoom werk, het vroeër vanjaar die bever se genoom in volgorde gerangskik ter viering van Kanada se 150ste verjaardag. “Die meeste van ons pogings is op menslike genome,”, het wetenskaplike Stephen Scherer vir my gesê. Maar dit stimuleer ons eintlik intellektueel om verder te kyk as wat ons doen. Want soms is goeie openbare betrekkinge 'n goeie rede as enige ander.

Papadum, die San Clemente-bok wie se genoom vroeër vanjaar met ’n nuwe tegniek herbou is. (Brian L. Sayre)

Oor Kat Eschner

Kat Eschner is 'n vryskut -wetenskap- en kultuurjoernalis in Toronto.


Inhoud

Die DNS-volgorde-metodes wat in die 1970's en 1980's gebruik is, was handmatig, byvoorbeeld Maxam-Gilbert-volgordebepaling en Sanger-volgordebepaling. Verskeie hele bakteriofage- en dierlike virale genome is volgens hierdie tegnieke opeenvolg, maar die verskuiwing na vinniger, outomatiese volgordebepalingsmetodes in die negentigerjare het die opeenvolging van die groter bakteriële en eukariotiese genome vergemaklik. [10]

Die eerste organisme wat sy hele genoom georden het, was Haemophilus influenzae in 1995. [11] Daarna is die genome van ander bakterieë en sommige archaea vir die eerste keer opgestel, hoofsaaklik as gevolg van hul klein genoomgrootte. H. influenzae het 'n genoom van 1 830 140 basispare DNA. [11] Daarteenoor het eukariote, beide eensellige en meersellige soos Amoeba dubia en mense (Homo sapiens) onderskeidelik, het baie groter genome (sien C-waarde paradoks). [12] Amoeba dubia het 'n genoom van 700 miljard nukleotiedpare wat oor duisende chromosome versprei is. [13] Mense bevat minder nukleotiedpare (ongeveer 3,2 miljard in elke kiemsel - let op die presiese grootte van die menslike genoom word nog hersien) as A. dubia hul genoomgrootte oorskry egter die genoomgrootte van individuele bakterieë. [14]

Die eerste bakteriese en argaeale genome, insluitend dié van H. influenzae, is met die volgorde van Shotgun opgevolg. [11] In 1996 is die eerste eukariotiese genoom (Saccharomyces cerevisiae) is op volgorde. S. cerevisiae, 'n modelorganisme in die biologie het 'n genoom van slegs ongeveer 12 miljoen nukleotiedpare, [15] en was die eerste eensellige eukariote om sy hele genoom in volgorde te hê. Die eerste meersellige eukariote, en dier, om sy hele genoom in volgorde te hê, was die aalwurm: Caenorhabditis elegans in 1998. [16] Eukariotiese genome word deur verskeie metodes georden, insluitend Haelgeweer-volgordebepaling van kort DNS-fragmente en volgordebepaling van groter DNS-klone vanaf DNS-biblioteke soos bakteriese kunsmatige chromosome (BACs) en gis-kunsmatige chromosome (YACs). [17]

In 1999 is die hele DNS-volgorde van menslike chromosoom 22, die kortste menslike outosoom, gepubliseer. [18] Teen die jaar 2000 is die tweede dier- en tweede ongewerwelde (nog eerste insek) genoom opgevolg - dié van die vrugtevlieg Drosophila melanogaster - 'n gewilde keuse van modelorganisme in eksperimentele navorsing. [19] Die eerste plantgenoom - dié van die modelorganisme Arabidopsis thaliana - is ook teen 2000 in volle volgorde geplaas. [20] Teen 2001 is 'n konsep van die hele menslike genoomvolgorde gepubliseer. [21] Die genoom van die laboratoriummuis Muskulus is in 2002 voltooi. [22]

In 2004 het die Human Genome Project 'n onvolledige weergawe van die menslike genoom gepubliseer. [23] In 2008 het 'n groep van Leiden, Nederland, die volgordebepaling van die eerste vroulike menslike genoom (Marjolein Kriek) gerapporteer.

Selle wat gebruik word vir die opeenvolging van redigering

Byna enige biologiese monster wat 'n volledige kopie van die DNS bevat—selfs 'n baie klein hoeveelheid DNS of antieke DNS—kan die genetiese materiaal verskaf wat nodig is vir volledige genoomvolgordebepaling. Sulke monsters kan speeksel, epiteelselle, beenmurg, hare insluit (solank die hare 'n haarfollikel bevat), sade, plantblare of enigiets anders wat selle bevat wat DNA bevat.

Die genoomvolgorde van 'n enkele sel wat uit 'n gemengde populasie selle gekies word, kan bepaal word deur gebruik te maak van tegnieke van enkelvoudige genoom volgordebepaling. Dit hou belangrike voordele in in omgewingsmikrobiologie in gevalle waar 'n enkele sel van 'n spesifieke mikro-organisme spesie deur mikroskopie uit 'n gemengde populasie geïsoleer kan word op grond van sy morfologiese of ander onderskeidende eienskappe. In sulke gevalle kan die normaalweg nodige stappe van isolasie en groei van die organisme in kultuur weggelaat word, wat sodoende die volgordebepaling van 'n veel groter spektrum van organismegenome moontlik maak. [24]

Enkelcelgenoomvolgorde word getoets as 'n metode van voorimplantasie genetiese diagnose, waarin 'n sel uit die embrio wat deur in vitro -bevrugting geskep is, geneem en ontleed word voordat die embrio na die baarmoeder oorgedra word. [25] Na inplanting kan selvrye fetale DNA deur middel van eenvoudige aderpunksie van die moeder geneem word en vir heelgenoomvolgordebepaling van die fetus gebruik word. [26]

Vroeë tegnieke Wysig

Die opeenvolging van byna 'n hele menslike genoom is vir die eerste keer in 2000 bewerkstellig, deels deur gebruik te maak van haelgeweervolgorde -tegnologie. Alhoewel die volledige genoom haelgeweer -opeenvolging vir klein (4000–7000 basispaar) genome reeds in 1979 in gebruik was, het [27] die breër toepassing baat gevind by twee -eindige opeenvolging, in die volksmond bekend as volgorde van 'n dubbele loop haelgeweer. Namate volgordebepalingsprojekte langer en meer ingewikkelde genome begin aanneem het, het verskeie groepe begin besef dat nuttige inligting verkry kan word deur albei kante van 'n fragment van DNS te volgorde. Alhoewel die volgorde van beide kante van dieselfde fragment en die byhou van die gepaarde data volg meer omslagtig was as om 'n enkele uiteinde van twee afsonderlike fragmente te volg, was die kennis dat die twee rye in teenoorgestelde rigtings georiënteer was en ongeveer die lengte van 'n fragment afgesien van elke ander was waardevol in die rekonstruksie van die volgorde van die oorspronklike doelfragment.

Die eerste gepubliseerde beskrywing van die gebruik van gepaarde eindes was in 1990 as deel van die opeenvolging van die menslike HPRT -lokus, [28] hoewel die gebruik van gepaarde punte beperk was tot die sluiting van gapings na die toepassing van 'n tradisionele haelgeweer -volgordebepalingsbenadering. Die eerste teoretiese beskrywing van 'n suiwer paarsgewys eindvolgorde strategie, met die veronderstelling dat fragmente van konstante lengte was, was in 1991. [29] In 1995 is die vernuwing van die gebruik van fragmente van verskillende groottes bekendgestel, [30] en getoon dat 'n suiwer paarsgewys eindvolgorde strategie sou moontlik wees op groot teikens. Die strategie is daarna deur die Instituut vir Genomiese Navorsing (TIGR) aanvaar om die hele genoom van die bakterie te orden. Haemophilus influenzae in 1995, [31] en daarna deur Celera Genomics om die hele vrugtevlieggenoom in 2000 te volg, [32] en daarna die hele menslike genoom. Applied Biosystems, nou Life Technologies genoem, vervaardig die outomatiese kapillêre opeenvolgers wat deur Celera Genomics en The Human Genome Project gebruik word.

Huidige tegnieke Redigeer

Alhoewel kapillêre volgordebepaling die eerste benadering was om 'n byna volle menslike genoom suksesvol te volg, is dit steeds te duur en neem dit te lank vir kommersiële doeleindes. Sedert 2005 is kapillêre volgordebepaling geleidelik verplaas deur hoë-deurset (voorheen "volgende generasie") volgordebepalingtegnologieë soos Illumina kleurstofvolgordebepaling, pyrosevolgordebepaling en SMRT-volgordebepaling. [33] Al hierdie tegnologieë gebruik steeds die basiese haelgeweerstrategie, naamlik parallelisering en sjabloonopwekking via genoomfragmentasie.

Ander tegnologieë verskyn, insluitend nanopoortegnologie. Alhoewel nanopore-volgordebepalingstegnologie nog steeds verfyn word, is die draagbaarheid en potensiële vermoë om langlesings te genereer relevant vir volgorde-volgorde-toepassings van die hele genoom. [34]

Analise Wysig

In beginsel kan volledige genoomvolgordebepaling die rou nukleotiedvolgorde van 'n individuele organisme se DNA verskaf. Verdere analise moet egter uitgevoer word om die biologiese of mediese betekenis van hierdie volgorde te verskaf, soos hoe hierdie kennis gebruik kan word om siektes te voorkom. Metodes vir die ontleding van volgorde -data word ontwikkel en verfyn.

Omdat volgordebepaling baie data genereer (daar is byvoorbeeld ongeveer ses biljoen basispare in elke menslike diploïede genoom), word die uitset daarvan elektronies gestoor en vereis 'n groot hoeveelheid rekenaarkrag en bergingskapasiteit.

Alhoewel die ontleding van WGS -data stadig kan wees, is dit moontlik om hierdie stap te bespoedig deur toegewyde hardeware te gebruik. [35]

'N Aantal openbare en private ondernemings ding mee om 'n volledige genoomopvolgplatform te ontwikkel wat kommersieel robuust is vir navorsing en kliniese gebruik, [36] insluitend Illumina, [37] Knome, [38] Sequenom, [39] 454 Life Sciences, [40] Pacific Biosciences, [41] Complete Genomics, [42] Helicos Biosciences, [43] GE Global Research (General Electric), Affymetrix, IBM, Intelligent Bio-Systems, [44] Life Technologies, Oxford Nanopore Technologies, [45 ] en die Beijing Genomics Institute. [46] [47] [48] Hierdie maatskappye word swaar gefinansier en gerugsteun deur waagkapitaliste, verskansingsfondse en beleggingsbanke. [49] [50]

'N Algemene kommersiële mikpunt vir die volgorde van koste tot die laat 2010's was $ 1000, maar die private ondernemings werk daaraan om 'n nuwe doelwit van slegs $ 100 te bereik. [51]

Aansporing wysig

In Oktober 2006 het die X-prysstigting, in samewerking met die J. Craig Venter Wetenskapstigting, die Archon X-prys vir genomika gestig, [52] met die bedoeling om $10 miljoen toe te ken aan "die eerste span wat 'n toestel kan bou en dit kan gebruik om 100 menslike genome binne 10 dae of minder te volg, met 'n akkuraatheid van nie meer as een fout in elke opeenvolgende 1.000.000 basisse nie, met rye wat ten minste 98% van die genoom akkuraat dek, en teen 'n herhalende koste van nie meer as $ 1.000 per genoom nie ". [53] Die Archon X-prys vir Genomika is in 2013, voor die amptelike begindatum daarvan, gekanselleer. [54] [55]

Geskiedenis Redigeer

In 2007 het Applied Biosystems 'n nuwe tipe sequencer genaamd SOLiD System begin verkoop. [56] Die tegnologie het gebruikers in staat gestel om 60 gigabases per lopie te volg. [57]

In Junie 2009 het Illumina aangekondig dat hulle hul eie persoonlike volledige genoomvolgordediens op 'n diepte van 30× vir $48 000 per genoom bekendstel. [58] [59] In Augustus het die stigter van Helicos Biosciences, Stephen Quake, verklaar dat hy met behulp van die maatskappy se Single Molecule Sequencer sy eie volle genoom vir minder as $50 000 in volgorde bepaal het. [60] In November publiseer Complete Genomics 'n eweknie-geëvalueerde referaat in Wetenskap demonstreer sy vermoë om 'n volledige menslike genoom vir $1,700 te volgorde. [61] [62]

In May 2011, Illumina lowered its Full Genome Sequencing service to $5,000 per human genome, or $4,000 if ordering 50 or more. [63] Helicos Biosciences, Pacific Biosciences, Complete Genomics, Illumina, Sequenom, ION Torrent Systems, Halcyon Molecular, NABsys, IBM, and GE Global appear to all be going head to head in the race to commercialize full genome sequencing. [33] [64]

With sequencing costs declining, a number of companies began claiming that their equipment would soon achieve the $1,000 genome: these companies included Life Technologies in January 2012, [65] Oxford Nanopore Technologies in February 2012, [66] and Illumina in February 2014. [67] [68] In 2015, the NHGRI estimated the cost of obtaining a whole-genome sequence at around $1,500. [69] In 2016, Veritas Genetics began selling whole genome sequencing, including a report as to some of the information in the sequencing for $999. [70] In summer 2019 Veritas Genetics cut the cost for WGS to $599. [71] In 2017, BGI began offering WGS for $600. [72]

However, in 2015 some noted that effective use of whole gene sequencing can cost considerably more than $1000. [73] Also, reportedly there remain parts of the human genome that have not been fully sequenced by 2017. [74] [75] [76]

DNA microarrays Edit

Full genome sequencing provides information on a genome that is orders of magnitude larger than by DNA arrays, the previous leader in genotyping technology.

For humans, DNA arrays currently provide genotypic information on up to one million genetic variants, [77] [78] [79] while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000 times more data. Because of this, full genome sequencing is considered a disruptive innovation to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their consumables cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500 per 1 million basepairs). [40]

Mutation frequencies Edit

Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. [80] [81] An even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical twins) 100-year-old centenarians. [82] Only 8 somatic differences were found, though somatic variation occurring in less than 20% of blood cells would be undetected.

In the specifically protein coding regions of the human genome, it is estimated that there are about 0.35 mutations that would change the protein sequence between parent/child generations (less than one mutated protein per generation). [83]

In cancer, mutation frequencies are much higher, due to genome instability. This frequency can further depend on patient age, exposure to DNA damaging agents (such as UV-irradiation or components of tobacco smoke) and the activity/inactivity of DNA repair mechanisms. [ aanhaling nodig ] Furthermore, mutation frequency can vary between cancer types: in germline cells, mutation rates occur at approximately 0.023 mutations per megabase, but this number is much higher in breast cancer (1.18-1.66 somatic mutations per Mb), in lung cancer (17.7) or in melanomas (≈33). [84] Since the haploid human genome consists of approximately 3,200 megabases, [85] this translates into about 74 mutations (mostly in noncoding regions) in germline DNA per generation, but 3,776-5,312 somatic mutations per haploid genome in breast cancer, 56,640 in lung cancer and 105,600 in melanomas.

The distribution of somatic mutations across the human genome is very uneven, [86] such that the gene-rich, early-replicating regions receive fewer mutations than gene-poor, late-replicating heterochromatin, likely due to differential DNA repair activity. [87] In particular, the histone modification H3K9me3 is associated with high, [88] and H3K36me3 with low mutation frequencies. [89]

Genome-wide association studies Edit

In research, whole-genome sequencing can be used in a Genome-Wide Association Study (GWAS) - a project aiming to determine the genetic variant or variants associated with a disease or some other phenotype. [90]

Diagnostic use Edit

In 2009, Illumina released its first whole genome sequencers that were approved for clinical as opposed to research-only use and doctors at academic medical centers began quietly using them to try to diagnose what was wrong with people whom standard approaches had failed to help. [91] In 2009, a team from Stanford led by Euan Ashley performed clinical interpretation of a full human genome, that of bioengineer Stephen Quake. [92] In 2010, Ashley’s team reported whole genome molecular autopsy [93] and in 2011, extended the interpretation framework to a fully sequenced family, the West family, who were the first family to be sequenced on the Illumina platform. [94] The price to sequence a genome at that time was US$19,500, which was billed to the patient but usually paid for out of a research grant one person at that time had applied for reimbursement from their insurance company. [91] For example, one child had needed around 100 surgeries by the time he was three years old, and his doctor turned to whole genome sequencing to determine the problem it took a team of around 30 people that included 12 bioinformatics experts, three sequencing technicians, five physicians, two genetic counsellors and two ethicists to identify a rare mutation in the XIAP that was causing widespread problems. [91] [95] [96]

Due to recent cost reductions (see above) whole genome sequencing has become a realistic application in DNA diagnostics. In 2013, the 3Gb-TEST consortium obtained funding from the European Union to prepare the health care system for these innovations in DNA diagnostics. [97] [98] Quality assessment schemes, Health technology assessment and guidelines have to be in place. The 3Gb-TEST consortium has identified the analysis and interpretation of sequence data as the most complicated step in the diagnostic process. [99] At the Consortium meeting in Athens in September 2014, the Consortium coined the word genotranslation for this crucial step. This step leads to a so-called genoreport. Guidelines are needed to determine the required content of these reports.

Genomes2People (G2P), an initiative of Brigham and Women's Hospital and Harvard Medical School was created in 2011 to examine the integration of genomic sequencing into clinical care of adults and children. [100] G2P's director, Robert C. Green, had previously led the REVEAL study — Risk EValuation and Education for Alzheimer's Disease – a series of clinical trials exploring patient reactions to the knowledge of their genetic risk for Alzheimer's. [101] [102]

In 2018, researchers at Rady Children's Institute for Genomic Medicine in San Diego, CA determined that rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. The researchers reported a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42 P = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting. [103]

Rare variant association study Edit

Whole genome sequencing studies enable the assessment of associations between complex traits and both coding and noncoding rare variants (minor allele frequency (MAF) < 1%) across the genome. Single-variant analyses typically have low power to identify associations with rare variants, and variant set tests have been proposed to jointly test the effects of given sets of multiple rare variants. [104] SNP annotations help to prioritize rare functional variants, and incorporating these annotations can effectively boost the power of genetic association of rare variants analysis of whole genome sequencing studies. [105]

The introduction of whole genome sequencing may have ethical implications. [106] On one hand, genetic testing can potentially diagnose preventable diseases, both in the individual undergoing genetic testing and in their relatives. [106] On the other hand, genetic testing has potential downsides such as genetic discrimination, loss of anonymity, and psychological impacts such as discovery of non-paternity. [107]

Some ethicists insist that the privacy of individuals undergoing genetic testing must be protected. [106] Indeed, privacy issues can be of particular concern when minors undergo genetic testing. [108] Illumina's CEO, Jay Flatley, claimed in February 2009 that "by 2019 it will have become routine to map infants' genes when they are born". [109] This potential use of genome sequencing is highly controversial, as it runs counter to established ethical norms for predictive genetic testing of asymptomatic minors that have been well established in the fields of medical genetics and genetic counseling. [110] [111] [112] [113] The traditional guidelines for genetic testing have been developed over the course of several decades since it first became possible to test for genetic markers associated with disease, prior to the advent of cost-effective, comprehensive genetic screening.

When an individual undergoes whole genome sequencing, they reveal information about not only their own DNA sequences, but also about probable DNA sequences of their close genetic relatives. [106] This information can further reveal useful predictive information about relatives' present and future health risks. [114] Hence, there are important questions about what obligations, if any, are owed to the family members of the individuals who are undergoing genetic testing. In Western/European society, tested individuals are usually encouraged to share important information on any genetic diagnoses with their close relatives, since the importance of the genetic diagnosis for offspring and other close relatives is usually one of the reasons for seeking a genetic testing in the first place. [106] Nevertheless, a major ethical dilemma can develop when the patients refuse to share information on a diagnosis that is made for serious genetic disorder that is highly preventable and where there is a high risk to relatives carrying the same disease mutation. Under such circumstances, the clinician may suspect that the relatives would rather know of the diagnosis and hence the clinician can face a conflict of interest with respect to patient-doctor confidentiality. [106]

Privacy concerns can also arise when whole genome sequencing is used in scientific research studies. Researchers often need to put information on patient's genotypes and phenotypes into public scientific databases, such as locus specific databases. [106] Although only anonymous patient data are submitted to locus specific databases, patients might still be identifiable by their relatives in the case of finding a rare disease or a rare missense mutation. [106] Public discussion around the introduction of advanced forensic techniques (such as advanced familial searching using public DNA ancestry websites and DNA phenotyping approaches) has been limited, disjointed, and unfocused. As forensic genetics and medical genetics converge toward genome sequencing, issues surrounding genetic data become increasingly connected, and additional legal protections may need to be established. [115]

The first nearly complete human genomes sequenced were two Americans of predominantly Northwestern European ancestry in 2007 (J. Craig Venter at 7.5-fold coverage, [116] [117] [118] and James Watson at 7.4-fold). [119] [120] [121] This was followed in 2008 by sequencing of an anonymous Han Chinese man (at 36-fold), [122] a Yoruban man from Nigeria (at 30-fold), [123] a female clinical geneticist (Marjolein Kriek) from the Netherlands (at 7 to 8-fold), and a female caucasian Leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues). [124] Steve Jobs was among the first 20 people to have their whole genome sequenced, reportedly for the cost of $100,000. [125] As of June 2012 [update] , there were 69 nearly complete human genomes publicly available. [126] In November 2013, a Spanish family made their personal genomics data publicly available under a Creative Commons public domain license. The work was led by Manuel Corpas and the data obtained by direct-to-consumer genetic testing with 23andMe and the Beijing Genomics Institute). This is believed to be the first such Public Genomics dataset for a whole family. [127]


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Marsupials versus mammals

Marsupials, our mammalian brethren, are found mostly in Australia and New Guinea. They have many weird features that separate them from other mammals, including a very short pregnancy, after which they shelter their very immature offspring in a pouch.

Sequences of the kangaroo and other marsupials have shed light on how these features have developed after the placental mammal-marsupial split 150 million years ago. The genome sequencing of an opossum and a small kangaroo species called the tammar wallaby show that the group may have evolved in South America, not Australia.

Analysis of the tammar wallaby genome indicates that large areas of the marsupial genome are similar to the genome of normal, placental mammals.


Human Genome Sequencing: Approaches and Applications

A list of different methods used for mapping of human genomes is given below. These techniques are also useful for the detection of normal and disease genes in humans.

1. DNA sequencing : Physical map of DNA can be identified with highest resolution.

2. Use of probes : To identify RFLPs, STS and SNPs.

3. Radiation hybrid mapping: Fragment genome into large pieces and locate markers and genes. Requires somatic cell hybrids.

4. Fluorescence in situ hybridization (FISH) : To localize a gene on chromosome.

5. Sequence tagged site (STS) mapping : Applicable to any part of DNA sequence if some sequence information is available.

6. Expressed sequence tag (EST) mapping : A variant of STS mapping expressed genes are actually mapped and located.

7. Pulsed-field gel electrophoresis (PFGE) : For the separation and isolation of large DNA fragments.

8. Cloning in vectors (plasmids, phages, variable lengths, cosmids, YACs, BACs).: To isolate DNA fragments of variable length.

9. Polymerase chain reaction (PCR) : To amplify gene fragments.

10. Chromosome walking : Useful for cloning of overlapping DNA fragments (restricted to about 200 kb).

11. Chromosome jumping : DNA can be cut into large fragments and circularized for use in chromosome walking.

12. Detection of cytogenetic abnormalities : Certain genetic diseases can be identified by cloning the affected genes e.g. Duchenne muscular dystrophy.

13. Databases : Existing databases facilitate gene identification by comparison of DNA and protein sequences.

For elucidating human genome, different approaches were used by the two HGP groups. IHCSC predominantly employed map first and sequence later approach. The principal method was hierarchical shotgun sequencing. This technique involves fragmentation of the genome into small fragments (100-200 kb), inserting them into vectors (mostly bacterial artificial chromosomes, BACs) and cloning. The cloned fragments could be sequenced.

Celera Genomics used whole genome shotgun approach. This bypasses the mapping step and saves time. Further, Celera group was lucky to have high-throughput sequenators and powerful computer programmes that helped for the early completion of human genome sequence.

Whose Genome was Sequenced?

One of the intriguing questions of human genome project is whose genome is being sequenced and how will it relate to the 6 billion or so population with variations in world? There is no simple answer to this question.

However, looking from the positive side, it does not matter whose genome is sequenced, since the phenotypic differences between individuals are due to variations in just 0.1% of the total genome sequences. Therefore many individual genomes can be used as source material for sequencing.

Much of the human genome work was performed on the material supplied by the Centre for Human Polymorphism in Paris, France. This institute had collected cell lines from sixty different French families, each spanning three generations. The material supplied from Paris was used for human genome sequencing.

Human Genome Sequence -Results Summarised:

The information on the human genome projects is too vast, and only some highlights can be given below. Some of them are briefly described.

Major Highlights of human Genome:

1. The draft represents about 90% of the entire human genome. It is believed that most of the important parts have been identified.

2. The remaining 10% of the genome sequences are at the very ends of chromosomes (i.e. telomeres) and around the centromeres.

3. Human genome is composed of 3200 Mb (or 3.2 Gb) i.e. 3.2 billion base pairs (3,200,000,000).

4. Approximately 1.1 to 1.5% of the genome codes for proteins.

5. Approximately 24% of the total genome is composed of introns that split the coding regions (exons), and appear as repeating sequences with no specific functions.

6. The number of protein coding genes is in the range of 30,000-40,000.

7. An average gene consists of 3000 bases, the sizes however vary greatly. Dystrophin gene is the larget known human gene with 2.4 million bases.

8. Chromosome 1 (the target human chromosome) contains the highest number of genes (2968), while the Y chromosome has the lowest. Chromosomes also differ in their GC content and number of transposable elements.

9. Genes and DNA sequences associated with many diseases such as breast cancer, muscle diseases, deafness and blindness have been identified.

10. About 100 coding regions appear to have been copied and moved by RNA-based transposition (retro- transposons).

11. Repeated sequences constitute about 50% of the human genome.

12. A vast majority of the genome (

97%) has no known functions.

13. Between the humans, the DNA differs only by 0.2% or one in 500 bases.

14. More than 3 million single nucleotide polymorphisms (SNPs) have been identified.

15. Human DNA is about 98% identical to that of chimpanzees.

16. About 200 genes are close to that found in bacteria.

Most of the Genome Sequence is Identified:

About 90% of the human genome has been sequenced. It is composed of 3.2 billion base pairs (3200 Mb or 3.2 Gb). If written in the format of a telephone book, the base sequence of human genome would fill about 200 telephone books of 1000 pages each. Some other interesting analogs/ sidelights of genome are given in Table 12.3.

Individual differences in genomes:

It has to be remembered that every individual, except identical twins, have their own versions of genome sequences. The differences between individuals are largely due to single nucleotide polymorphisms (SNPs). SNPs represent positions in the genome where some individuals have one nucleotide (i.e. an A), and others have a different nucleotide (i.e. a G). The frequency of occurrence of SNPs is estimated to be one per 1000 base pairs. About 3 million SNPs are believed to be present and at least half of them have been identified.

Benefits/Applications of Human Genome Sequencing:

It is expected that the sequencing of human genome and the genomes of other organisms will dramatically change our understanding and perceptions of biology and medicine. Some of the benefits of human genome project are given.

Identification of human genes and their functions:

Analysis of genomes has helped to identify the genes, and functions of some of the genes. The functions of other genes and the interaction between the gene products needs to be further elucidated.

Understanding of polygenic disorders:

The biochemistry and genetics of many single- gene disorders have been elucidated e.g. sickle-cell anemia, cystic fibrosis, and retinoblastoma. A majority of the common diseases in humans, however, are polygenic in nature e.g. cancer, hypertension, diabetes. At present, we have very little knowledge about the causes of these diseases. The information on the genome sequence will certainly help to unravel the mysteries surrounding polygenic diseases.

Improvements in gene therapy:

At present, human gene therapy is in its infancy for various reasons. Genome sequence knowledge will certainly help for more effective treatment of genetic diseases by gene therapy.

Improved diagnosis of diseases:

In the near future, probes for many genetic diseases will be available for specific identification and appropriate treatment.

Development of pharmacogenomics:

The drugs may be tailored to treat the individual patients. This will become possible considering the variations in enzymes and other proteins involved in drug action, and the metabolism of the individuals.

Genetic basis of psychiatric disorders:

By studying the genes involved in behavioural patterns, the causation of psychiatric diseases can be understood. This will help for the better treatment of these disorders.

Understanding of complex social trait:

With the genome sequence now in hand, the complex social traits can be better understood. For instance, recently genes controlling speech have been identified.

Knowledge on mutations:

Many events leading to the mutations can be uncovered with the knowledge of genome.

Better understanding of developmental biology:

By determining the biology of human genome and its regulatory control, it will be possible to understand how humans develop from a fertilized eggs to adults.

Vergelykende genomika:

Genomes from many organisms have been sequenced, and the number will increase in the coming years. The information on the genomes of different species will throw light on the major stages in evolution.

Development of biotechnology:

The data on the human genome sequence will spur the development of biotechnology in various spheres.


Kyk die video: Origins of Genus HomoAustralopiths and Early Homo; Variation of Early Homo; Speciation of Homo (Augustus 2022).