Textbook of Personalized Medicine - Second Edition [2015]

59

The role of SNPs in clinical trials is:

• Genotyping is important in design and interpretation of clinical studies.
  Advantages of molecular genetic profi ling in clinical studies are:


• It is a contribution to molecular defi nition of the disease


• Correlation of drug response to the genetic background of the patient


• Prediction of dose-response and adverse effects


• SNP mapping data can be used to pinpoint a common set of variant nucleotides
  shared by people who do not respond to a drug.

Genotyping and Haplotyping

A genotype is the genetic constitution of an organism as defi ned by genetic and
molecular analysis and covers the complete set of genes. Genotyping can be used
for determination of relevant genetic variation in each of the two parental
chromosomes in an individual.
Haplotypes are gene versions that represent the genetic variations as they occur
on each pair of chromosome in an individual. This term has been redefi ned as a
genetic bar code with each line representing a SNP. Gene-based haplotypes are
comprised of a sequence of nucleotides (~25,000) that occur at SNP positions on a
single chromosome at the locus of a single gene. Haplotypes are the most precise
markers possible for a given gene because they contain all the variations in a gene.
Haplotypes contain more information than unorganized SNPs and for practical pur-
poses one has to deal with a dozen or fewer haplotypes for each gene. Thus, fewer
patients are needed to detect statistically signifi cant correlation to drug response
than if SNP genotyping is used alone. This forms the basis of developing personal-
ized or individualized therapy.

GENE

SEQUENCE

SNP

DISCOVERY

HAPLOTYPE

ASSEMBLY

GENOTYPING

METHOD

CLINICAL

CORRELATION

PHARMACOGENETIC

PROFILE

PERSONALIZED

© Jain PharmaBiotech MEDICINE

Fig. 2.6 Role of SNPs in personalized medicine

SNP Genotyping