The recent report in Science that mutations in the Dicer gene underlie Familial Pleuropulmonary Blastoma has all the hallmarks of a classic scientific discovery. Perseverance, dedication, compassion and brilliant scientific insight combined to yield a spectacular advance in cancer genetics. Dicer is an enzyme that is essential to the expression of a new class of non-coding genes called microRNAs. These microRNAs are powerful pleotropic effectors capable of dramatically altering the growth and differentiation of human cells. The authors show that mutations in the Dicer gene lead to this pediatric lung cancer. Thus, this is another remarkable example of the burgeoning linkage between the new biology of the non-coding human genome and disease. Indeed, one suspects that mutations in Dicer may well be associated with other more common human cancers.
The Need for a Grass Roots Genomics Movement
However, one begins to suspect that, in the future, such advances will only be made by a “ grassroots genomics movement”. It is a sad fact that many families, like the one in the study published in Science, suffer in silence from the tragically predictable consequences of their hereditary disease. Unfortunately, in general, such families remain unknown to the general biomedical research community. Firstly this is an information problem. Unless, the family represents an index case, their history is unlikely to be described in the literature. Secondly, it is because the major funding agencies believe that the study of rare disease will not have a significant impact on human health. Indeed, most federal research grant applicants assert the significance of the proposed studies by indicating the prevalence of the disease. Compounding this problem is the reluctance of most research grant applicants to propose to do truly innovative research. This problem has been recently discussed in an excellent article in the NY Sunday Times. Perhaps the time has come for a “grass roots” family based genomics movement. Much of the personalized genome discussion has focused on the DNA sequence of an individual. Now is the time to focus on genomic studies of families. With the dramatic decrease in the cost of whole genome sequencing, families with hereditary disease can now take the initiative and sequence their genomes. The alternative is to painfully wait until their hereditary disease attracts the attention of biomedical research.
This movement should not be confined to families with rare hereditary disease. The factors that regulate the penetrance of mutations in genes that are already known to underlie common genetic diseases (for example the BRCA1 gene and cancer) are far from clear. Family initiated sequence analysis studies may identify such factors and thereby refine the diagnosis.
Can it be done?
Some might say that this might be a difficult agenda. Indeed, the sequencing of the first human genome required the talents of a generation of the finest molecular biologists and considerable federal funding. However, many of the barriers have now been broken. Collection of DNA no longer requires a skilled phlebotomist and can be achieved by a simple cheek swab. The family will not need to operate or bear the cost of running a research lab. There are now several genomic sequence vendors who provide a sequencing service for around $20,000 per sample and an insight into the relevance of any sequence variants. The cost of sequencing 20 family members (including those affected and unaffected) is therefore much less than a typical R01 federal research grant. Families could form an “institute without walls” and directly apply for federal research grants. Their ability to provide a hereditary disease database might provide compelling preliminary data. As is typical of many grant applications, the collaboration with an established medical geneticist will provide both skills in grant preparation and in the interpretation of the sequence data.
It’s good science
Although it may be difficult at present to interpret the genome of an individual, the presence of a putative disease variant within a family should be much more readily tractable. It is important to point out that successful gene identification studies on families typically require a much smaller N than that required for GWAS studies on more heterogeneous populations. It is very likely that the identification of disease variants will garner the interest of experts in the biology of that gene and accelerate the development of therapeutic agents.
Thus, in sum, this movement will not only enhance a family’s ability to make sound healthcare decisions but also advance science.
![Reblog this post [with Zemanta]](http://img.zemanta.com/reblog_e.png?x-id=d71f0917-e731-485a-befc-c861fa5897f9)
