NEW YORK, Feb 13 – Variagenics has been issued a patent for its proprietary haplotyping methods for determining differences in DNA polymorphisms between maternal and paternal chromosomes, the company said Tuesday.
Determining specific polymorphism variations between the two copies of a person’s genome may be key to understanding how SNPs affect drug response. Since a particular gene can contain many SNPs, and the number and type of SNPs may vary greatly between the parental copies, the combinations of SNPs rather than the individual SNPs determines genetic variation in drug responses and disease susceptibility, the company said.
The patent, no.6,183,958, is entitled " Probes for Variance Detection," and describes a method for obtaining a probe that discerns whether polymorphisms in sequences vary between a person’s maternal and paternal copy of a gene.
The probes contain many identical versions of a unique, or mono-allelic, known sequence from cells. When a sample of unknown DNA is added to these probes and heated up to unzip, the sequence from this DNA will hybridize to the probe. If the sequence does not totally hybridize, it will contain a bump in the mismatched pair of nucleotides, or heteroduplex, which scientists can detect using an enzyme called a resolvase, said Vincent Stanton, scientific vice president at Variagenics.
If all of the samples tested have the same heteroduplexes, then both copies of chromosomal DNA are identical in this region being tested. But if part of the DNA contains different heteroduplexes than anther part, these copies differ. The probe can detect exactly how and where these differences exist in the sequences, Stanton said.
“That’s important is to determine the set of SNPs in one chromosome vs. the other,” Stanton said. “The patent describes how you can use the patterns of cleavage” to do this.
Variagenics may license out this technology to any other company that wants to do haplotyping using heteroduplexes, and will use the probes in its own haplotyping systems, Stanton said.