Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
Standards Needed
The Utah Foundation for Biomedical Research's Gholson Lyon was busy in 2009, trying to identify the genetic causes behind a rare disease affecting baby boys in a family in Ogden, Utah. But, as he says in a Nature commentary, this week, he was hesitant to tell the family what he found because the research he did didn't follow the protocols required for validated clinical testing, and he wasn't sure the individual results were accurate.
The expansion of genomics into medicine is showing that it's time for researchers to "create a formalized protocol akin to the rigorous process that doctors and other health-care workers go through during any clinical lab test, which practically eliminates the chances of mistakes and mix-ups," Lyon says. "In this way, when participants want to know what we know, we will feel confident that what we tell them is correct." Scientists conducting human genetics research are not under CLIA regulations, he adds, but perhaps there should be a similar standard for researchers. "This means establishing suitable guidelines for the collection, tracking and sequencing of DNA samples from human participants, along with training health-care professionals in genetics counseling," Lyon writes.
As the director of a
As the director of a CLIA-certified laboratory that does genetic testing, who previously was a researcher at the NIH doing gene discovery in rare Mendelian diseases, I can assure you that research laboratories are VERY far from having any kind of appropriate formalized protocols. However, the cost and personnel requirements to set-up and maintain a CLIA environment greatly exceeds the budget of any research laboratory I know. I do not feel it is at all appropriate for research labs to turn themselves in CLIA labs (or something resembling them) when it is easy, straight-forward, and very inexpensive for the research lab to simply partner with a CLIA lab, who can confirm research findings in a CLIA environment, and provide a laboratory report suitable for inclusion in the patient/participant's medical recored.
It fair to say that there no
It fair to say that there no scope for taking a laid back attitude, either in academia of CLIA labs when it comes to clinical testing. Both Illumina and Life technologies are planning to take their genome sequencers to FDA for approval for diagnostic clinical sequencing. However, the technology (wet chemistry, software and hardware)has not matured to perfection but fast evolving to where sequence related conclusions could be made with confidence. The question is whether we should be using the data generated in non-CLIA environment for diagnostic/clinical decision making. My answer is that it depends on the question we ask. There are ample examples where genome sequencing in non-CLIA environment has saved patient lives or at least gave them a different treatment option. Till FDA finalizes on how to regulate genome sequencing for diagnostics and clinical decision making, it would be a mistake to put severe constrains on this technology which of course should be used judiciously.
Vishnu Mishra
Totally agree with the
Totally agree with the respondent who encourages partnerships between research and clinical labs for validation of assays and findings for use in clinical testing. Researchers frequently focus on a few patients or families that were part of their research discovery phase but do not have data about the clinical validity or clinical utility of their discoveries. Performance of these high-complexity tests require a lab director with board-certification per CLIA regulations. There are extensive guidance documents written about all of these aspects. I recall a researcher asking if he could send a tech over to my CAP-accredited genetic testing lab "for an hour" to learn how to make their lab CLIA certified. Yeah, right.
Yeah, right...for sure!! Ha
Yeah, right...for sure!! Ha Ha!!
Always the problem when you don't even know how much you don't even know.
As the Product Manager at
As the Product Manager at Horizon Diagnostics this touches on our drive to developing genetically defined molecular diagnostic reference standards.
There is a large variability in the sensitivity of current genetic tests. This occurs between labs, between platforms, between genotypes and even between different users within a lab.
We are currently working with the key players to bring standardization for these platforms in Molecular Pathology and addressing this very serious issue. Please contact me if you would like more information (jonathan.frampton@horizondiscovery.com)