Posted on 10/20/2004 8:03:13 PM PDT by PeaceBeWithYou
Tailored therapies to target a range of diseases, such as diabetes and breast cancer, may be a step closer after the final draft of the gene-rich part of the "human book of life" was published yesterday.The sequence provides a blueprint of the genes that make life possible and is accurate to only one error in 100,000 "letters" of code, an article in the journal Nature reveals.
Analysis of the new data shows that the human genome, which is the entire genetic map of an organism, contains between 20,000 and 25,000 genes. Surprisingly, the number of genes is possibly only 5,000 more than that of the nematode worm, one of the simplest organisms on the planet.
Of the genes that have been identified, 1,183 were only recently discovered by a process known as "gene duplication".
Scientists also found that 37 genes seem to have recently "died" by developing a mutation that made them non-functional, although it does not affect human development.
The work, which was conducted by the International Human Genome Sequencing Consortium (IHGSC), builds on the historic publication of the first draft of the whole human genome in 2001. The publicly funded IHGSC and the private company Celera announced completion of the first drafts in jointly published papers three years ago.
However, the drafts were some way off being perfect, as both groups were missing about 10 per cent of what is known as the "euchromatin" - the crucial gene-rich portion of the genome.
Genes are sequences of DNA that provide the coded instructions for making proteins. Other parts of the genome consist of DNA but not genes.
Dr Jane Rogers, the head of DNA sequencing at the Cambridge-based Sanger Institute, which conducted much of the work for the first draft in 2001, explained: "What we find in the human genome is that the majority of it is made from a fairly unique gene-containing sequence, and this is what is known as the euchromatic part.
"That holds the information that provides the codes for proteins and the regulation of their production. This is important because it provides most of the instructions to make the materials that we humans consist of."
The sequence, published throughout the world yesterday, is estimated to cover 99 per cent of the gene-containing part of the genome. It has just 341 gaps remaining and consists of unbroken runs of code averaging 38 million bases - the chemical "letters" that make up DNA.
The IHGSC scientists wrote in Nature: "The genome sequence reported here should serve as a firm foundation for biomedical research in the decades to come.
"It allows systematic searches for the causes of disease - for example, to find all key heritable factors predisposing to diabetes or ... mutations underlying breast cancer - with confidence that little can escape detection."
Dr Rogers wrote: "That this draft is again missing a small portion of the euchromatin does not mean that the information is unusable.
"Making this sequence available to researchers from the outset has really stimulated biological exploration and changed the way that researchers carry it out.
"So instead of starting with needing to identify a piece of DNA that has an effect, they will actually go to the database first and look for the sequence and start their experiments from there.
"Small pieces are still missing throughout the genome, and it is of the utmost importance that we now try and find those.
"We are now trying to define where variations occur in the human genome that we can then say are causative for disease. If we can do that reliably, that would then allow us to look in populations of people who have specific diseases and see if we can observe the changes that occur in the genome.
"If we do see the changes it will then tell us if it is the reason for the disease. There is some prospect in future for the potential for gene therapy if we need to replace a gene, and there are many more opportunities as well. For example, if we have a mutation that affects some sort of metabolising enzyme, a patient might not respond to one type of drug very well, but they could respond to another. Having that information could direct the prescription of drugs to be far more effective."
Professor Robin Lovell-Badge, the head of developmental genetics at the National Institute for Medical Research in London, wrote: "This will greatly increase our understanding of what happens in cases of genetic disease and issues about interaction between genes and environment.
"If you take heart disease or certain types of diabetes, people who suffer from strokes and even behavioural problems, these are all likely to be influenced by a combination of different genes. Knowing what the full set of genes are is an incredibly useful starting point to gaining knowledge of what causes those ailments.
"We can also begin to discover why some people respond well to certain drugs, and others do not, which is clearly influenced by genetics.
"All these things will be enormously helped by having the full sequence, as it used to take years to find a single gene responsible for conditions such as cystic fibrosis. Now we can just consult the database."
In an accompanying article, Dr Lincoln Stein, from the Cold Spring Harbor Laboratory in New York, said the finished gene sequence had roughly doubled the total time and cost of the human genome project.
He wrote: "Does it contribute anything new to our understanding of the genome? It does indeed, and to prove the point the authors of the current paper describe several large-scale analyses of the genome that would have been difficult to perform on the draft sequence. Absolute completeness [of the sequencing project] will be elusive, but ... obtaining the substantial majority of the information will greatly accelerate the pace of biomedical research in thousands of laboratories."
Dr Stein concluded: "In sequencing the human genome, the researchers have already climbed mountains and travelled a long and winding road.
"But we are only at the end of the beginning: ahead lies another mountain range that we will need to map out and explore as we seek to understand how all the parts revealed by the genome sequence work together to make life."
In an accompanying Nature paper, scientists led by Dr Evan Eichler, from the University of Washington in Seattle, said the new sequence showed up shortcomings in the technique used by Celera.
The company took a controversial shortcut called the "whole genome shotgun method", which involved blasting apart the genome, sequencing random fragments, and using a computer to fit them together like pieces of a jigsaw puzzle.
Dr Eichler’s team found that the technique missed many duplicated DNA regions and may not provide an accurate picture of the genome.
Much of our DNA is disposable, study suggests
Mice, and probably humans, can survive despite having whole pages of DNA ripped out of their "book of life", scientists claimed yesterday.
Researchers deleted more than two million bases - the chemical "letters" of the DNA code - from the mouse genome. To the surprise of the scientists, the mice shrugged off the loss and were virtually unaffected.
The deleted sequences were from regions of the genome not known to have any essential function. Eddy Rubin, the director of the Joint Genome Institute in Walnut Creek, California, where the work was carried out, said: "We were looking particularly for sequences that might not be essential. Nonetheless, we were surprised, given the magnitude of the information being deleted from the genome, by the complete lack of impact noted.
"From our results, it would seem that some non-coding sequences may, indeed, have minimal, if any, function."
Controversy surrounds the DNA "desert" that makes up 98 per cent of the human genome.
Genes are sequences of DNA that provide the essential instructions for making proteins. But large swathes of DNA exist between the genes that appear to be barren wasteland with no purpose.
Some experts believe this "junk" DNA may not be as useless as it seems and plays a hidden role. But the new research, published in the journal Nature, indicates that large parts of the genome really are disposable.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.