Free Personal Genome, with a Catch
27/04/10 12:35 Filed in: GenomeWeb Daily Scan
Submitted by S. Pelech - Kinexus on Mon, 11/22/2010 - 02:18.
It's really amazing to see all of the hype about the mass sequencing of thousands of human genomes, even if it will soon only cost a thousand dollars or less for each. While we are all about 99.6% genetically identical, there can be profound consequences of SNP variations amongst individuals in limited cases. Nevertheless, at the protein level there is an incredible amount of feedback and redundancies to compensate for variations in protein performance as a result of these SNP changes.
Genotype does not equal phenotype as the environment plays an equally critical role in the development of most known diseases. Less than 2.5% of the human genome appears to encode about 23,000 different proteins, which appear in perhaps over 100,000 alternative splicing forms and are subject to extensive post-translational modifications. For example, there appears to be as many as 500,000 phosphorylation sites in human proteins, which act as on/off switches to regulate the activities, interactions and degradation of proteins. Genome sequencing does not provide this information. The complex interplay of proteins is only hinted with genomic analyses.
It is ludicrous to think that we can correlate complex human behaviours and disease manifestations primarily with genomic data. At best, such data might have some utility for prediction of the health risks of large populations, but it will be fairly useless for individual diagnoses and prognoses except for a very small number of cases. Moreover, such information may not be very helpful to individuals if there are no effective treatments available. During complex embryonic development, the most serious of genetic defects are identified and these pregnancies are naturally terminated early on. Decades of epidemiology studies without the benefit of genomics analyses have already uncovered critical environmental factors to promote wellness and reduce the risk of disease.
A deluge of genomic data is drowning researchers and to a large part is already ignored by the vast majority of investigators. It seems that the mass gene sequencing efforts will only serve to make the hay stack of data magnitudes larger so it will become even more difficult to weed through and find useful discoveries rather than false leads. More effort should be expended on making sense of the genomic data at hand rather than working to accumulate even more redundant sequencing data faster. The recently published reports of the poor performance of well documented biomarker SNP's for prediction of development of cancer in two separate large clinical studies seriously calls into question the whole enterprise.
The availability of a personal genomic sequence will probably generate more grief than benefit. For one thing, a significant portion of the population may find out that one or more of their parents are not who they thought they were. For another, the added stress from the psychological impact from the knowledge that one's genome harbors perhaps hundreds of SNP's that have been suspected to contribute to disease will probably have greater impact than the actual SNP's. For the vast majority of people with limited knowledge of biochemistry, the actual data from their sequenced genomes will be completely meaningless except for something to brag about with their friends that they have been gene sequenced. Surely the funding to sequence genomes on mass could be better spent on more productive avenues of research that are much more likely to be translational.
Link to the original blog post
It's really amazing to see all of the hype about the mass sequencing of thousands of human genomes, even if it will soon only cost a thousand dollars or less for each. While we are all about 99.6% genetically identical, there can be profound consequences of SNP variations amongst individuals in limited cases. Nevertheless, at the protein level there is an incredible amount of feedback and redundancies to compensate for variations in protein performance as a result of these SNP changes.
Genotype does not equal phenotype as the environment plays an equally critical role in the development of most known diseases. Less than 2.5% of the human genome appears to encode about 23,000 different proteins, which appear in perhaps over 100,000 alternative splicing forms and are subject to extensive post-translational modifications. For example, there appears to be as many as 500,000 phosphorylation sites in human proteins, which act as on/off switches to regulate the activities, interactions and degradation of proteins. Genome sequencing does not provide this information. The complex interplay of proteins is only hinted with genomic analyses.
It is ludicrous to think that we can correlate complex human behaviours and disease manifestations primarily with genomic data. At best, such data might have some utility for prediction of the health risks of large populations, but it will be fairly useless for individual diagnoses and prognoses except for a very small number of cases. Moreover, such information may not be very helpful to individuals if there are no effective treatments available. During complex embryonic development, the most serious of genetic defects are identified and these pregnancies are naturally terminated early on. Decades of epidemiology studies without the benefit of genomics analyses have already uncovered critical environmental factors to promote wellness and reduce the risk of disease.
A deluge of genomic data is drowning researchers and to a large part is already ignored by the vast majority of investigators. It seems that the mass gene sequencing efforts will only serve to make the hay stack of data magnitudes larger so it will become even more difficult to weed through and find useful discoveries rather than false leads. More effort should be expended on making sense of the genomic data at hand rather than working to accumulate even more redundant sequencing data faster. The recently published reports of the poor performance of well documented biomarker SNP's for prediction of development of cancer in two separate large clinical studies seriously calls into question the whole enterprise.
The availability of a personal genomic sequence will probably generate more grief than benefit. For one thing, a significant portion of the population may find out that one or more of their parents are not who they thought they were. For another, the added stress from the psychological impact from the knowledge that one's genome harbors perhaps hundreds of SNP's that have been suspected to contribute to disease will probably have greater impact than the actual SNP's. For the vast majority of people with limited knowledge of biochemistry, the actual data from their sequenced genomes will be completely meaningless except for something to brag about with their friends that they have been gene sequenced. Surely the funding to sequence genomes on mass could be better spent on more productive avenues of research that are much more likely to be translational.
Link to the original blog post