‘In a recent issue of Nature,  the landmark paper has appeared that describes and discusses the finished version ('build 35') of the human genome. This International Human Genome Sequencing Consortium's new build of the genome sequence is as finished as current technology allows, which is a major improvement on the initial draft sequence. The finished version of the genome sequence covers 2.85 Gbp or 99% of the euchromatic region, with only 341 gaps, compared to the 150 000 in the working draft. It has a long-range continuity of 39.5 Mb, which is 475 times better than the 81 kb in the working draft, and the sequence has been delivered at an error rate of 1 10-5: almost 10 times better than the quality standard of 10-4 originally aimed for…The authors of this landmark paper emphasize the extremely rigorous quality control applied to achieve and validate this result. And rightly so, this sequence will be the raw material upon which future generations of scientists and healthcare workers will base studies that depend on highly reliable data. To this aim, 40 Mb was independently resequenced, and an overlap study was carried out on 4235 clones from one large insert library. As hoped for, the latter showed a bimodal distribution of base differences, consistent with half of these coming from one haplotype and half from the other. These results confirm that the sequencing error rate is 20100 times lower than the human polymorphism rate. This confirms the finished human genome sequence as a robust resource for large-scale evolutionary, functional and comparative analyses. The Consortium also resequenced 750 000 clones (8 coverage) from an independent fosmid library to validate over 97% of the junctions of the large insert clones. This analysis also suggests the presence of 50100 erroneous deletions (average 5 kb).’ European Journal of Human Genetics, 2005

‘The biological code crackers sequencing the human genome have said they have finished the job - two years ahead of schedule. Their announcement came less than three years after a "rough draft" was published to worldwide acclaim...The decoding is now close to 100% complete…American institutions have been the major partners in the decoding programme. When the Human Genome Project was formally launched, there were some who thought it could take 20 years or more to complete. But robotics and supercomputers speeded up the process hugely… The purpose of the last three years has been to fill in gaps in the DNA sequence and "proof read" the data to produce a "gold standard" that will inform genetic research for years to come. Jane Rogers, head of sequencing at the Sanger Institute, said: “We have reached the limits we set on this project, achieving tremendously high standards of quality much more quickly than we hoped. The working draft allowed researchers to kick-start a multitude of biomedical projects. Now they have a highly polished end product which will assist them even more. It's a bit like moving on from a first-attempt demo music tape to a classic CD," she said…Identifying genes can now be done in days instead of years.’ Ivan Noble, BBC News Online, 2003

Finishing the euchromatic sequence of the human genome - The international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers 99% of the euchromatic genome and is accurate to an error rate of 1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human genome seems to encode only 20,00025,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead… Because the precise scientific plan and the feasible degree of accuracy and completeness were unclear at the outset, the sequencing of the human genome proceeded in phases… Notably, the finishing phase required roughly equal resources of time and expense as the draft phase.’ Human Genome Sequencing Consortium, 2004

Revealing the Human Genome

Such a staggering spillage of secrets -

this walnut-cracking, slow unlocking

of a sacred, long buried biological box,

which we didn’t even know had a lid -

yielding key, cipher - sealed centuries

of blood and death’s fruitful sampling;

Evolutionary time capsule

still roaming modern Earth.

Such rushing into unaccustomed light -

sequencers, processors, spewing pattern,

curious letter fountain in electric air,

for the whole world’s artificial eye -

like finding light has a skeleton,

white bone - aeons before bone,

the honed dream of first light

that commanded itself to be -

and was, illumined even in the cup

of darkness, a shut eye dreaming -

discovering it came from families of light -

pinprick to star to heavenly recipe; sampled

in burning salmon sunset - summer honey

filling sugared flowercups; lickable, sticky

gold of autumn afternoons, the mussel-stomach

colour enchanting the Western Isles at evening.

Like finding dark has skeleton – exoskeleton;

soft blue skull like a squashy baby fontanelle

hardening at late evening under navy skin,

to glossy black turtle - crawling with stars.

The human being is now unspooling

animal skins, our old cast costumes -

our glorious burning tiger robe,

dazzling, missing swan wings -

eye-flower, leaf-palm,

our foot-root, bat-arm -

beyond example flesh,

the enormity of atoms,

marvellous weight of existence;

excising to what remains - left

held in the scientist’s palm

like a magic seed of light -

a description using light

because there is no word,

no suitable explanation,

existing simple symbol,

for the original Word,

which just is; yes - is.

A nest of letters,

written in light -

cocooned in darkness,

dreaming always, life -

translated by computers

trying to learn grace; art.

‘… the successful completion this month of all of the original goals of the Human Genome Project (HGP) emboldens the launch of a new phase for genomics research, to explore the remarkable landscape of opportunity that now opens up before us. Like Shakespeare, we are inclined to say, “what’s past is prologue” (The Tempest, Act II, Scene 1). If we, like bold architects, can design and build this unprecedented and noble structure, resting on the firm bedrock foundation of the HGP (Figure 2), then the true promise of genomics research for benefiting humankind can be realized. “Make no little plans; they have no magic to stir men’s blood and probably will themselves not be realized. Make big plans; aim high in hope and work, remembering that a noble, logical diagram once recorded will not die, but long after we are gone will be a living thing, asserting itself with ever-growing insistency” (attributed to Daniel Burnham, architect).’ A Vision for the Future of Genomics Research, Francis S Collins, Eric D Green, Alan E Guttmacher & Mark S Guyer on behalf of the US National Human Genome Research Institute, Nature, 2003

‘Owing to the emphasis on thoroughness, validation and QC, the flavor of the [Human Genome Sequencing Consortium] paper is rather more technical than the mainly biology-oriented working draft publication, which was therefore, unsurprisingly, more electrifying. …. One revisited issue is the human gene count. This is corrected to an estimate of 22 500 (range 2025 000): downwards from the already surprisingly low estimate of 31 000 in the working draft.’ European Journal of Human Genetics, 2005

Coaxing our ghost from skin wall,

bone helmet, wild animal, flower;

pattern among drapes of existence -

furred, spotted, fleshed; the running

glory of them to our pinnacle eye -

grown slowly in the rumbling belly

of time, from death’s foetal waters,

stories of continual fertilising birth –

into dazzling light, comes brighter light,

like the skeleton of a star, heart of a star,

star-seed. We have caught ourselves

in the process of life, computer-held,

coagulated a moment - not frozen,

as the Genome is always evolving;

never a Gingerbread man, static pattern,

but man becoming - a work-in-progress,

like water pausing as mercury -

river as silver ribbon from afar

for the benefit of comprehension;

possibility of process, perception.

We have deduced ourselves,

our living poetry, nature -

poetry that speaks our name;

all others - living and dead -

animal, man, fish, plant -

shown to be one structure.

For some it's the sense of completion. For others it's the importance of getting it right. Either way, the completion of the human genome project in time for the fiftieth anniversary of the discovery of DNA's helical  structure is attended by many sighs of relief… Two groups of scientists revealed draft versions of the human DNA sequence: one from a private company, one from an international and publicly funded consortium. Labs involved in the latter have been slogging to fill the holes ever since. Today they are announcing closure: 98% of the regions that actually contain genes are done…Some bits remain elusive; for unknown reasons, current molecular-biology tools cannot get the better of them. Whether or not the details actually matter is "a matter of bar room fistfights", says Branscomb. But there is pressure to be accurate because this sequence serves as a reference to which people's genomes are compared.’ Helen Pearson, Nature, 2003

The world will hold collective breath a moment;

TV food hang cooling, hooked on frozen fork -

before treacherous sinking sands of everyday,

duty’s ambush; television, bills and pleasure -

our tailored sorrows, fitted panniers on our back,

eclipse interest blinkers, illuminated attention -

snuff wonder, humbling perspective; that stirring -

as we avoid the shattering night beauty of stars.

‘…researchers have reached the halfway point in dotting the i's and crossing the t's of the genetic sentences describing how to build a human. The newly finalised chromosome 5 is the 12th chromosome to be completed, with 12 more to go. As the new sequence reveals, this chromosome is a genetic behemoth containing key disease genes and a wealth of information about how humans evolved…Chromosome 5, the largest to be completed thus far, is made up of 180.9 million genetic letters – the As, Ts, Gs, and Cs that compose the genetic alphabet. Those letters spell out the chromosome's 923 genes, including 66 genes that are known to be involved in human disease. Another 14 diseases seem to be caused by chromosome 5 genes, but they haven't yet been linked to a specific gene. Other chromosome 5 genes include a cluster that codes for interleukins, molecules that are involved in immune signalling and maturation and are also implicated in asthma. Hidden in the chromosome 5 sequence are clues to how humans evolved after branching away from chimpanzees. On average, the chromosome is more than 99 per cent similar between chimpanzees and humans, with the greatest similarity found in genes that cause diseases when mutated... Moving evolutionarily further away, about one-third of chromosome 5 is similar to a chicken chromosome that determines the chicken's sex, much like the X and Y chromosomes in humans. This finding backs up previous research suggesting that before mammals and birds split 300 million years ago, the sex chromosomes had not yet evolved. After the split, mammals and birds developed their own methods of creating males and females. One duplicated region on chromosome 5 could eventually help explain how spinal muscular dystrophy is inherited.’ Wellcome Trust, 2004

Slowness, at enormous speed -

Slowness, at enormous speed -

war against inaccurate darkness,

to bring this amazing thing to light,

good hands. Orphaned from life -

isolated script, deducible chemistry;

the dissection of beauty, expression

shaking hands with shifting skeleton,

which is silver; shining - promising

Earth and all her creatures -

new unity and understanding.

From the circus-masters, our animal

preserved, free - from taxidermists -

scrap-merchants, white-coated vultures,

we have cradled our mighty monument;

dream, hope, idea, thought, action,

discussion, argument, race, draft -

trumpets, labour, refinement;

completion, more refinement…

chromosome by chromosome now,

the Genome will not stop yielding.

‘Even more detailed annotations and analyses have already been published for chromosomes 5, 6, 7, 9, 10, 13, 14, 19, 20, 21, 22 and Y. Publications describing the remaining 12 chromosomes are forthcoming.’ Wellcome Trust Sanger Institute, 2004

‘Biological research increasingly depends on 'finished' genome sequences. Deducing what is absent from these sequences is not trivial. More than 99% of the euchromatic portion of the human genome is now represented as a high-quality finished sequence with each base ordered and oriented. However, two principal types of gap remain: heterochromatic (estimated to be  200 Mb) and euchromatic (23.0 Mb) gaps. Here, we use various global sources of data to help understand the nature of the gaps in the finished human genome. Not all gaps are recalcitrant to subcloning, nor are most heterochromatic. The presence of recent segmental duplications is the most important predictor of gap location in euchromatic sequences. The resolution of these regions remains an important challenge for the completion of the human genome, gene annotation and SNP assignment.’ An assessment of the sequence gaps: Unfinished business in a finished human genome, Nature, 2004

‘Dr Francis Collins, the scientist leading the Human Genome Project, says he expects important new gene sequences governing aspects of personality, such as intelligence and behaviour, to be known very shortly. While the project to crack our DNA code has been targeted at understanding and eradicating disease, Dr Collins believes the project will provide significant insights into a broad range of heritable aspects. "We haven't discovered most of those yet, but frankly, we should be prepared for an avalanche of that kind of information coming in the next two or three years," he told the BBC World Service's The Interview programme. "On top of the Human Genome Project, which laid out the letters of the code in a 'reference DNA sequence' way, we now have a very good encyclopaedia of the variable parts. "Researchers are using those in very powerful ways, to track down the specific genes involved in very complicated things - including intelligence," said the director of the US National Human Genome Research Institute. Dr Collins stressed that understanding the genes governing behaviour was not the main focus of the Human Genome Project. Instead, it remains firmly focussed on identifying the faulty genes responsible for disease, such as diabetes, heart disease, and cancer.’ BBC, 2006

Note from the author
exploring the project

    The Human Genome Project (1)
    The Word
    Genetic Transcription
    & Translation
    Nature of the Genome
    All Life is One

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