Resolving the variable genome and epigenome in human disease - Knight - 2012 - Journal of Internal Medicine
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Conclusions
There
is no doubt that recent advances in genomics, currently driven by new
high-throughput sequencing techniques, are taking us to remarkable new
levels in our understanding of the human genome, and the genetic and
epigenetic variation that exists, with important implications for our
understanding of human disease. As this knowledge grows, our
appreciation of the complexity with which we are faced is also
underlined. For common multifactorial traits, GWAs have been very
informative but leave much heritable risk unresolved. Rarer variants may
prove important but in general, more integrated approaches are needed
in which environmental risk factors are considered and combined with
functional genomic analyses. Moreover, we need to derive functional
genomic data in a disease-relevant setting as the consequences of
underlying genetic and epigenetic diversity are increasingly recognized
to be highly context specific.
Current
technologies that can interrogate the whole genome carry with them
significant caveats: these tools are new, and successful application to
important biological problems requires careful experimental design and
consideration of the limitations inherent in such approaches. The data
sets involved are highly complex, and analysis remains extremely
challenging with significant risks of false positive and negative
results until the field matures. High-throughput sequencing is not a
panacea but a critical tool in current genomics.
Used wisely, it is resolving the individual genome and epigenome, at a structural and functional level, and will radically advance our understanding of disease. For Mendelian traits (Wiki) , the impact is already being felt. For common multifactorial diseases, this may take a little longer.
Used wisely, it is resolving the individual genome and epigenome, at a structural and functional level, and will radically advance our understanding of disease. For Mendelian traits (Wiki) , the impact is already being felt. For common multifactorial diseases, this may take a little longer.
