Sleep/Circadian Rhythm SNP Gene Array Initiative
In a joint initiative on the “feasibility of a sleep/circadian
rhythms gene chip” at the NIH workshop held in Bethesda, MD on April
10-12, 2008 (see Workshop flyer), the
group strongly endorsed the development of a sleep/circadian rhythm SNP
gene array chip.
An SNP array is a type of DNA microarray which is used
to detect polymorphisms within a population. A single nucleotide polymorphism
(SNP), a variation at a single site in DNA, is the most frequent type
of variation in the genome. There are around 10 million SNPs that have
been identified in the human genome. As SNPs are highly conserved throughout
evolution and within a population, the map of SNPs serves as an excellent
genotypic marker for research.
The most important application of an SNP array is in determining
disease susceptibility or resistance. In sleep research, for example, the sleep/circadian
rhythm SNP gene array chip could be used to indentify gene variants
conferring risk for circadian rhythm disorders or in differential susceptibility to sleep deprivation.
To spearhead the process of developing of a sleep/circadian
rhythm SNP gene array chip, the SRS Presidential Task Force on Genetics and Sleep was established.
The members of the Task Force are:
1. Joseph Bass, Northwestern University
2. Mary Carskadon, Brown University
3. Chiara Cirelli, University of Wisconsin-Madison
4. Thomas Kilduff, SRI International
5. Mirek Mackiewicz, University of Pennsylvania
6. Emanuel Mignot, Stanford University
7. Allan Pack, University of Pennsylvania (Chair of the Task Force)
8. Susan Redline, Case Western Reserve University
9. David Rye, Emory University
10. Clifford Saper, Harvard University
11. Joseph Takahashi, Northwestern University
12. Fred Turek, Northwestern University
13. Phyllis Zee, Northwestern University
The Task Force is charged with four tasks:
1. Determination of whether there should be a specific gene chip identified with SNPs from a selection
of genes that are likely to be involved in sleep and circadian disorders, which can be used to screen well
characterized clinical populations for specific gene mutations. If so, how many genes should be represented
on the chip, how many SNPs, and what should those be? Should the NIH be encouraged to assist the sleep
community with the development and distribution of these Sleep Gene Chips for the use by a broad range of
2. Determination of the current status of research definitions for all sleep disorders. If applicable,
propose a methodology that could be used to develop phenotypic definitions that would be used internationally
in studies of genetics of sleep.
3. Determination of whether the NIH should be encouraged to establish a nationwide system of Sleep Centers
that would agree on standardized ways to phenotype patients with sleep and circadian disorders. If so, what
types of clinical information (history, physical exam, basic laboratory tests) should be collected in a
standardized way? What types of specialized sleep studies should be done to establish the diagnoses, and are
there standardized ways in which this could be collected for comparison across centers?
4. Determination of the best method, going forward, to provide the underpinnings for a nationwide Genetics
and Sleep Initiative. What would be the best structure for such and initiative? Can this be done with private
funds, or will it require public funding?
If this becomes so large it could only be funded by the NIH, what should our strategies be in encouraging
and solidifying that support? Should there be an international component and if so how would that work if
the US component were NIH sponsored?
The written recommendations of the Task Force will be presented to the President of the
Sleep Research Society no later than February 14, 2009.
Based on the recommendations provided by the participants of the NIH workshop, the initial working group
that formed thereafter and the current Task Force members, a list of potential candidate genes for the SNP
sleep/circadian rhythms gene chip was developed (see attached file).
The following classes of genes are currently included on the list:
a. Genes identified in human studies where polymorphisms are associated
with different sleep/circadian phenotypes.
b. Genes identified in studies in model systems (rat, mice, fruit flies
etc.) where variants affect sleep/wake circadian phenotypes and response
to sleep deprivation.
c. Other genes in signaling pathways involving genes in (a) and (b).
d. Clock genes.
e. Genes for neuronal circuitry—neurotransmitters, neurotransmitter
receptors, relevant enzymes, relevant transporters.
f. Selected genes identified in microarray studies as being differentially
expressed in sleep wakefulness or after sleep deprivation. Priority should be given to genes
found in more than one microarray study (in the same species or different species).
g. Selected genes for relevant metabolic pathways.
You can comment on the sleep/circadian rhythms gene chip, propose
additional genes or suggest a gene be removed from the
list by sending e-mail message to: email@example.com.
To learn more about a similar initiative in the cardiovascular
field (i.e., IBC chip) follow this link: bmic.upenn.edu/cvdsnp/index.php