The major objective of establishing the EPR is to provide DNA from, and access to, individuals with clinically significant genotypes who might be willing to participate in follow-up studies. We are not aware of a resource such as this that is available to NIEHS investigators at this time, although there are many readily available anonymous DNA repositories. Some possible types of follow-up studies that might be proposed for EPR participants are described below. These will depend on the prevalence and potential biological significance of the specific polymorphisms and vary in hypothesis and study design.
- Simple assessment of SNP prevalence rates in this sample of Chapel Hill area residents, or in subgroups based on gender, age, or ethnicity and race.
- Haplotype determinations in genes of interest. haplotype determinations can be approximated by statistical methods and confirmed by biochemical methods, e.g. cloning and direct sequencing of alleles. This type of "re-contactable" subject resource would allow investigators to identify probands with the SNPs or haplotypes of interest, and then propose a new study to analyze these variants from family members of the proband.
- Biochemical determinations on samples from subjects with particular SNPs or haplotypes. This is envisioned as one of the most common uses of this database, in which the identification of subjects with a given SNP or haplotype will allow for the proposal of studies designed to test some biochemical attribute of the SNP or haplotype.
- A more ambitious use for this resource would be for common variants, in which a substantial fraction of this population expresses a given allele. In this situation, it would be possible to actually design prospective studies of disease risk based on the presence or absence of the mutation. The resource would provide data on matched controls for this type of study as well.
- Rare cases in which major gene alterations are correlated directly with phenotype. For example, one mutation encountered during the EGP in the gene ZFP36l1 results in a non-spliced mRNA, and complete failure of allelic expression. Since knockout of this gene in mice results in embryonic lethality, it seems possible that the hemizygous state might have a less severe phenotype. It might be possible to do direct genotype-phenotype correlations in families harboring this mutation.
Last Reviewed: July 22, 2015