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22
| 1 | 2008
Klinisk Biokemi i Norden
(Fortsat fra side 20)
sis has already contributed in medical diagnostics,
because many of these molecular markers can function
as biomarkers when associated with development or
predisposition to common diseases as well as indi-
vidual variations in drug response. One criterion to
prioritize a polymorphism for study is whether it has a
functional consequence.
Among variations being analyzed, SNPs seem to
be the most common type of genetic variation and
about 10 millions of SNPs (5) are now documented
in several dedicated databases free of charge. (http://
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=snp, SNP
BrowserTM v3.1, Applied Biosystems. The scientific
focus is now drifting towards how these SNPs co-
occur, how they interact to alter the function of a gene,
and which SNPs can eventually be used as biomarkers.
However, important to notice is that many reported
DNA variations have only been identified using a
few individuals and have not been strictly defined as
polymorphisms. Investigators may also take into con-
sideration that the allele frequency may vary dramatic
among ethnic groups.
A group of defined SNPs has already for sev-
eral years been utilized as biomarkers for diagnosis
of simple, single gene defects. Detection of SNPs
in for example the Coagulation Factor V (Leiden)
and the Prothrombin genes have been established
as routine analysis in coagulation defects (8;9), as
well as documented SNPs in the candidate genes for
Hypercholesterolemi, Hemochromatosis and Lactosis
intolerance (10;11).
The term haplotype may be useful when several
SNPs are identified surrounding the gene of interest.
Haplotypes refers to a combination of polymorphisms
in close proximity that are coinherited in many indi-
viduals in a population. Designing Haplotypes from a
distinct region may provide a more complete descrip-
tion of the different SNPs involved in the disease
studied, and databases for searching and generating
haplotypes are established (http://www.nhgri.nih.gov/
About_NHGRI/Der/haplotype/index.html). Since the
number of SNPs and haplotypes reported has increased
extensively the last years, the approach to seek for
good SNP biomarkers has been more challenging. As
complexity of the project proceeds, professional assist-
ance from dedicated technical staff (bioinformatics) is
strongly recommended.
Foto: Henrik Alfthan. Island.
