GENETIC DIVERSITY DOCUMENTED BY CELERA
GENETIC DIVERSITY DOCUMENTED BY CELERA
HERE WE GO!
Here's an article about Celera, the major private investigator
on the human genome project, beginning the process of discovering
the tiny but vast numbers of genetic individual differences between
people that lead to genetic diversity of all functions of the
body. We excitedly await the findings in the genes controlling
the FOKS in the decision-making apparatus leading to the Hypoism
Mapping Tiny Differences Genome Company Has Found 2.8 Million
W A S H I N G T O N, Sept. 13 - Celera Genomics Inc., the Maryland-based
company that is working to map every single human gene, said today
it had found 2.8 million of the little changes that make one person
different from another. These differences - known as single nucleotide
polymorphisms or SNPs - each represent a single change in the
3 billion letters that make up the human genetic code. For instance,
one person may have an "A" where another has a "C."
The announcement means Celera has outstripped the rival public
project to map the human genome, Craig Venter, president of Celera,
said in a telephone interview. "It is a far greater number
of SNPs than there are in the public databases," Venter said.
Earlier this month, the publicly funded Human Genome Project and
the public-private SNP consortium, which includes 10 major pharmaceutical
companies, announced that they had found 800,000 different SNPs
(pronounced "snips"). Venter said Celera had duplicated
400,000 of these in its 2.8 million. But the public project has
400,000 unique SNPs, which means 3.2 million SNPs are now known.
Promise of SNPS:
Scientists hope to eventually use these SNPs to find out why
one person develops heart disease and another does not, why some
women have a higher risk of breast cancer, and why some people
have side-effects from certain drugs. Most of these traits will
probably be caused by a combination of SNPs. Such a genetic trait
is known as a haplotype. But occasionally, a single SNP is linked
with disease. For instance, Venter said the 2.8 million SNPs that
Celera had found include a single letter change in a gene known
as APOe that makes people prone to heart disease. This change
had been known, but Venter said Celera's work confirmed it independently.
Venter, who was scheduled to announce his findings at a conference
of genomics researchers in Miami later today, said it will take
some time to determine which SNPs mean something and which are
just random differences. "We know precisely where they are,"
he said. "As we annotate the genome, we know whether they
are in protein regions ... or key regulatory regions. We will
know which ones have a chance of being associated with function."
Are Differences Important?
Proteins are the basic building blocks of the human body, so
changes there may have biological importance, Venter said. Those
that occur in regulatory regions may turn a gene on or off - also
of huge biological significance, Venter said. "A single change
could have profound impacts on protein expression," Venter
said. "It could lead to physiological changes and or disease."
But Venter stressed that it will take a great deal of research
to find which changes are important. "In most of us, most
of the traits and things that we have are due to combinations
of changes," he said. "The genetics community has made
such a big deal out of rare diseases and rare genes that people
assume that these are the standard. And they assume it is all
determinism, as well, which it isn't." Environmental factors,
such as age, diet and exposure to sunlight, combine with genes
to create changes such as ageing or disease in people. Celera
has made the information about the SNPs available to its subscribers,
which include drug companies and academic researchers who will
use the raw information to try and find biological meaning in
the SNPs. On Tuesday, Genaissance Pharmaceuticals, Inc. said its
researchers had found 12 different haplotypes that affected patients'
response to the asthma drug albuterol. Each was made up of a combination
of different SNPs.
NY Times: Study Breaks New Ground on Variations in Genome
Genaissance shows that on average, genes have 12 alleles each.
A large-scale study of the variability in the human genome has shown that each human gene may come in 12 different versions on average. The authors also say their findings cast doubt on the way that a large government and industry program is mining the genome for the genetic basis of common human diseases.
The study was undertaken by Genaissance Pharmaceuticals, a biotechnology company in New Haven, to discover the genetic basis for why individuals respond differently to given drugs.
The company's plan is to help doctors determine through a genetic test, rather than trial and error, which asthma or cholesterol drug, for example, would be best for a patient. The company has bought 60 of the latest-model DNA-sequencing machines, one of the largest sets outside those of the genome-sequencing centers, and installed them in a refurbished World War II munitions plant in New Haven.
The decoding of the human genome provided, in effect, a single DNA sequence. But what is of interest for most medical purposes is to know how each gene varies from one person to another and how those variations influence an individual's susceptibility to disease and response to drugs.
Government and industry have devoted considerable resources to looking for sites in the genome's three- billion-unit sequence where some people have one letter of DNA and some another. These sites of common variation are known as SNP's (pronounced snips). The hope is to correlate SNP's with disease and discover which versions of a gene predispose a person to diseases like diabetes or cancer.
So far three million or so SNP's have been cataloged, but they have been discovered more or less at random across the genome. Genaissance officials estimate that there are some 30 million SNP's in the human population, and say a SNP chosen at random is unlikely to pinpoint a gene variant that causes disease or drug response.
Instead, Genaissance is analyzing sets of closely bunched SNP's in the hope of correlating the patterns with a patient's response to various drugs. A connected set of SNP's inherited as a unit is called a haplotype, and so the company calls its method the haplotype approach.
Its ambition is to catalog the haplotypes of every human gene by decoding each gene in a total of about 90 people drawn from the three major human-population groups: Africans, Asians and Europeans. Company officials say they have already sequenced 4,000 of the estimated 30,000 human genes in this way and intend to sequence all of them within a few years.
Genaissance has published the results from 313 of these genes in today's issue of Science, in an article by Dr. J. Claiborne Stephens and several colleagues. From an analysis of the SNP's in these 313 genes, the authors calculate that each gene exists in 12 versions on average.
Dr. Kenneth Kidd, a population geneticist at Yale University who was not connected with the study, described the data as very important and said it confirmed how much genetic variability existed in the human population. He said he agreed with Genaissance's view that the SNP approach was "misconceived," and chided the government for having stripped ethnic identities from the panel of people whose genomes have been searched for SNP's.
But Dr. Francis Collins, director of the National Human Genome Research Institute, said the SNP and haplotype approaches were not in opposition. His institute plans a workshop next week, he said, on how to build a haplotype map of the genome. There may be quick ways of arranging the SNP's already discovered into the sets or haplotypes in which they are usually inherited.
Dr. Gualberto Ruaño, chief executive of Genaissance, said its haplotype catalog could help pharmaceutical companies to profile patients who respond best to their drugs, and to develop new drugs for any identified group of those who fail to respond.
Genetic information can be a delicate matter, particularly if it reveals a person's susceptibility to disease. Dr. Gerald F. Vovis, the company's chief technology officer, said Genaissance was developing information only about drug response, which in his view would fall into a less delicate category.
Both Dr. Kidd and Dr. David Altshuler of Harvard University said Genaissance was overcounting the number of SNP's and haplotypes, by including SNP's found in a single person. Because only common SNP's are likely to play a role in common diseases, geneticists usually count a DNA change as a SNP only it if occurs in at least 1 percent of a population. Many of the DNA changes Genaissance finds are singletons of perhaps no significance for any but the individual involved.
Nature Reviews Genetics 6, 668 (2005); doi:10.1038/nrg1703
Uniting human variation
It's becoming increasingly clear that polymorphism in the human genome goes way beyond SNPs. More and more studies are now identifying large-scale genomic variants — which include inversions, deletions and copy-number variants — as important components of normal human genetic variation. The Database of Genomic Variants aims to put all the information from these studies in one place.
The database is continually updated with information from both experimental data produced in-house by the research groups that curate it and from published studies. Just pick a chromosome and you are presented with a list of known variants, organized by location. Alternatively, you can enter the name of your favourite gene or region of the genome and the database will tell you if any identified variants are associated with it.
Useful graphical representations allow you to visualize where each variant lies in relation to cytological bands, coding regions and segmental duplications. The database also tells you the frequency of each variant, the method that was used to identify it and the ethnic backgrounds of the individuals in whom it was located. Links to gene databases and original papers make further investigations straightforward.
Once you've identified a variant of interest, the database also allows you to access a genome browser that provides more information about the surrounding genomic region. Here you can look for a range of features, including CpG islands, gene deserts, SNPs and segmental duplications.
As it expands, the database should help to piece together the contribution of large-scale polymorphisms to the genetic individualities that make each of us different.