Sequencing

Celera Sequencing - 60 million overlapping fragments, each 2,000 to 10,000 bases long,

Human Genome Project Sequencing - 22,000 fragments, each 100,000 to 300,000 bases long

Time to assemble 12,000 bases – 1980: more than a year; 1997 - 20 minutes; 2000 - one minute.

Figs, BBC Science Online

12 000 letters of DNA decoded by the Human Genome Project every second – 20 years previously, it had taken one year.

‘The Sanger Institute has more than 1500 devices installed on its network: more than 250 PCs and some Macintosh systems and a total of more than 700 64-bit Alpha processors. The Sanger Institute main sequence storage has more than 22 Terabytes (22,000 gigabytes) capacity. The system that serves sequence searches (the BLAST farm) has more than 400 nodes.’ Wellcome Trust Sanger Institute, UK,  where one third of Human Genome was sequenced

‘The method used for much of the genome is ‘shotgun sequencing’ which, in essence, involves breaking the genome up into conveniently sized chunks. The total size of the human genome is estimated to be about 3 billion base pairs, arrayed in 23 chromosomes. The chromosomes themselves are 50-250 million bases (megabases) long, too large to be sequenced directly (automated machines sequence fragments of between 400 and 700 bases), so the Human Genome Project fragments them into chunks of about 150 kilobases. Each of these large clones is then ‘shotgunned’ - broken into pieces of perhaps 1500 base pairs, either by enzymes or by physical shearing - and the fragments are sequenced separately. Shotgunning the original large clone randomly several times ensures that some of the fragments will overlap; computers then analyse the sequences of these small fragments, looking for end sequences that overlap - indicating neighbouring fragments - and assembling the original sequence of the clone… The alternative approach, ‘whole-genome shotgun sequencing’, was first used in 1982 by the inventor of shotgun sequencing, Fred Sanger, while working on phages (viruses of bacteria). In this technique, which has been used by the commercial company Celera Genomics, the whole genome is broken into small fragments that can be sequenced then reassembled. Although this approach can be highly automated and efficient - and has been very successful for the sequencing of the genomes of microorganisms and the fruitfly Drosophila - reassembling the fragments from the human genome is far more difficult and requires powerful computers.’ Wellcome Trust

Human Genome Project – Method (1)

It began, turning blind earth -

unknown geography, contours,

continents; panning sea - mining

air; hunting nuggets with needles,

teaspoons, in sluggish light,

glow-worms in dense night.

Then forks, ladles, spades;

buckets, diggers, trawlers -

storm lamps, growing brighter -

eagle eye transplanted to mole;

octopus arms to singing whale -

spotlight burning to lighthouse,

starlight seeding sun,

supernova, sunspots -

until bright nuggets strung;

sparkling, twitching beads

on silver strings -

life’s memorials

to the living and dead;

senseless knowledge

of order, space, materials -

chemical wire pulling pearls.

Spirit-pattern, matter unrealised,

insubstantial chimera of being -

spinning intricacy from simplicity -

uncovered, now revealed, displayed,

like a body put to bed in pure acid -

only known to us as mind translates

Sun to smiles - snowflakes and stars

rendered into their shining skeletons.

‘Francis Collins is a committed Christian and heads the publicly-funded National Human Genome Research Institute (NHGRI) in Washington DC, US…His professional reward, he says, comes when he discovers something that “the creator knew ahead of time - that's one of the aspects of my existence I wouldn't trade for anything”.’ BBC News

Working on the Human Genome

I am working in the realm of Grace -

when I hang up my bright white coat,

its hollow arms fall sloppily warm,

droop open like tired wings - shine

under dazzling laboratory light.

I have been borrowed, loaned -

when I return from my labour

to familiar family and friends,

my tongue babbles white smiles;

I think when I touch my children

you will see this character silver 

dripping from my loving fingers -

like the blood of mercury, nectar,

printing invisibly as kisses print,

shining their interior molecules -

because I have touched the divine.

I think they will see it -

in the pupils of my eyes,

like an infection of stars, love-scar,

because I have witnessed the divine;

so carefully unwrap the packaging,

to see the holy, golden gifts inside,

stripped of skin and shape.

And yet, I am there too -

all shining, shimmer-shivery,

as if stepped from the shower;

like a dripping silver ghost, indistinct -

then slipping even from this live ghost,

like a glorious embroidered robe -

and laughing aloud to see myself

only as code, known

as Word and light -

message and meaning;

love-print in the world.

All this makes me feel wonderful; as if

I come home looking just like the Moon.

‘The International Human Genome Sequencing Consortium has published its scientific description of the finished human genome sequence, the product of the 13-year effort to read the information encoded in the human chromosomes that reached its culmination in 2003. The paper, which appears in the 21 October issue of the journal Nature, examines the current genome sequence, which contains 2.85 billion nucleotides, encompasses around 99 per cent of the euchromatic (or gene-containing) portion of the human genome and is 99.999 per cent accurate - 10 times more accurate than the original goal. Notably, the predicted total number of genes has fallen to just 22 287: 19 599 known protein-coding genes and a further 2188 sections of DNA predicted to be protein-coding genes. Original estimates of gene number when the draft genome sequence was released were between 30 and 40 000, a figure that was considered surprisingly small. "Only a decade ago, most scientists thought humans had about 100 000 genes. When we analysed the working draft of the human genome sequence three years ago, we estimated there were about 30 000 to 35 000 genes, which surprised many. “This new analysis reduces that number even further and provides us with the clearest picture yet of our genome," said NHGRI Director Francis Collins. "The availability of the highly accurate human genome sequence in free public databases enables researchers around the world to conduct even more precise studies of our genetic instruction book and how it influences health and disease." ‘Finished' doesn't mean that the human genome sequence is perfect. There still remain 341 gaps in the finished human genome sequence, in contrast to the 150 000 gaps in the  working draft…’ Wellcome Trust Sanger Institute, 2004

Unearthing the Human Genome

Invading the sacredness of someone else’s bedroom top drawer -

women’s skin-powder dust, perfume ghosts; jewellery casualties

in gorgeous little velvet coffins, intestinal beads spilled, the blind

rings with lost eyes; brooches still pinning granny’s face - crippled,

bloody lipsticks, ancient silk limpening at the heart of lace - button

amputees clinging hopefully to threads, so desperate to feel needles

again in those aching holes, be re-united with dead mother garments.

The keys that haunt everybody – (if only we could find all the things

they open, close; the world - our lives, would be easier to understand).

Maybe tickets for a show – a boat, castle, years ago. Love words

and poems bleeding black and blue through skinny yellow paper;

cheesy souvenir thimble, horrible ribbon bows from forced necks

of momentous flowers - loud scarves slithering, slowly coming back

into fashion; pills for a forgotten illness with illegible doctor’s script,

safety-pins a-waiting sartorial danger; all these odd things washed up

from a life into the drawer, as sand passively takes all-comers – not

asking why, what for, just lays them out like starfish hands, accepts;

gradually becoming person-spelled, printed, like church icons slowly

growing holy. Imagine invading the sacredness of an egg, without

smashing, sawing, slicing. Think of the shape, perfect inviolability,

except for butting sperm inveigling mammal egg, promising cargo,

half-written letter by special delivery; the letterbox opening, healing,

as new life writes on the seemingly empty page - but magic happens,

lemon-juice writing, cocktail-shaking, spinning – an automaton body

making itself as mystery and grace hover like the breath of a lake;

halo, light anchored in a shining object - knowing skin boundaries

but not of them. The rooted, composted, whirring of letters shifting,

reforming - machine-knitting original patterns but incorporating still

Cable, Fair Isle, Turtle Neck. Patiently designing tiger fur, Einstein’s

brain, kingfisher wing, apple-belly; how to print love in a living eye.

Even beneath Plasticine’s pliable body -

before coming into warm moulding hands,

nimble fingers, multiple elastic fate;

mutability, passive form - material

at the heart of soft molecule,

to the inner nature of supple.

Even under thin star bones,

stuff of bone, white fibre -

to softness, cloud bone,

scaffold idea of bone -

white bone dream;

it is dark there -

everything unrealised, present -

like the absent breath of a ghost

inhabiting a prickling, cold room -

innocence of a black light switch

wired at the start of time -

where air is still dark space.

Now torches, spotlights shining

on the Genome’s many hearts -

all knowing in their history

each other’s beats and wars;

each one mother, son, sister, brother,

daughter to the other; genetic family,

the communal products of adaptation,

even collation of wrong information -

molecular meltdown, struggle and disease;

but always correcting or die in the attempt.

Always printing and editing - creating fantastic

patterns, chains; labour and success, developing

engineering, embroidering beauty; more

and more dazzling chemistry, creativity –

the tools of love, heart mechanics;

operation of eyes, hands blooming.

Like the tinkering watchmaker removing

the back, seeing unmistakeable artistry -

the mark, signature; instantly