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Many
companies are focused on developing high-density
genotyping arrays for studying genetic variation. Along
with available genomic sequencing data, this is leading
researchers closer to the possibility of personalized
medicine.
High
-Throughput Whole Genome
Arrays
Illumina,
Inc. has recently introduced two new products based on
their BeadChip technology (analyzes more than 317,000
SNPs via a single-tube, whole genomic amplification
process without PCR): the HumanHap300-Duo and the
HumanHap300-Duo+. According to the company, these are
the first multi-sample, whole genome arrays, with more
than 634,000 total tag SNPs (Single-Nucleotide
Polymorphism) per BeadChip. Tag SNPs selected from the
International HapMap Project enable SNP selection. The
Duo+ array allows for the addition of up to 60,000
custom SNP loci.
These
assays are ideal for loss of heterozygosity and
comparative hybridization studies (where normal and
disease samples are analyzed in parallel-as in cancer
research), and according to the company, will help
enable personalized medicine by correlating genetic
variation and gene function with specific disease
states.
Advances
in SNP Analysis
Another
recent technology advancement that will push SNP
genotyping forward is a 1-million SNP product. Recently
announced by Affymetrix, Inc. and developed in
collaboration with researchers at MIT and Harvard, the
new software will extract more information from each
array without any manufacturing or assay changes. The
company also announced it will be lowering the price of
its two-chip 500K SNP genotyping set by $250. This will
be offered as a single array by the end of this year,
increasing throughput. Both products are based on the
company’s Whole-Genome Sampling Assay (WGSA).
Multiplexing
is becoming more in demand for genetic analysis.
Sequenom, Inc. has announced its latest multiplex
genotyping assay, the iPLEX Gold Assay, which provides
routine multiplexing at 36x per reaction and up to 40x
depending on the complexity of the assay. This runs on
the company’s MassArray Compact System, a DNA analysis
platform that measures genetic target material and
variations. The iPLEX Gold will be available by the end
of this year and also as a service through the
company’s genetic analysis services unit.
New
Approaches
Several
companies have developed new technologies or adapted old
technologies for genotyping applications. Fluidigm has
developed a digital array for early cancer detection
research. The BioMark 12.765 array is based on a system
of channels and integrated valves to divide a mixture of
sample and PCR reagents into 765 nano-volume parts. This
enables detection of a somatic-cell point mutation in a
high background of similar sequences. Chris Heid,
director of marketing, says there are plans to apply
this technology for SNP analysis.
Adapting
the principles of flow cytometry, Luminex Corp.’s xMAP
technology uses a micron-sized microsphere with a
proprietary dying process to create 100 unique dye
mixtures in order to identify an individual microsphere.
It multiplexes up to 100 analytes in a single well.
Advantages include simultaneous analysis of different
bioassays (customizable for the user), real-time
analysis, and accurate quantification of biological
interactions. The company is focusing on licensing xMAP—Perkin
Elmer is using it to develop biomarker panels for drug
development and in vitro diagnostics.
Studies
Confirm and Validate
New Assays
BioTrove,
Inc. and Applied Biosystems, Inc. recently presented
data at the American Society of Human Genetics meeting
that validated their genotyping assays. BioTrove’s
OpenArray system (a high-throughput nanoliter-scale SNP
genotyping platform) confirmed that variation in the
NOS1AP gene is associated with cardiovascular mortality.
The 25,000-patient SNP genotyping association study was
conducted with researchers at Johns Hopkins School of
Medicine. Ongoing studies will search for additional
genetic sequences associated with cardiovascular
disease.
TaqMan
Drug Metabolism Genotyping Assays have been shown to
provide higher accuracy than other methods in
identifying gene variations that code for drug
metabolism enzymes. Researchers from Applied Biosystems,
Inc. and the National Cancer Institute demonstrated the
use of 2,400 markers from the assay panel in examining
genetic variation across the International HapMap
project and SNP500 cancer population. This validation
data is now publicly available through The
Pharmacogenetics and Pharmacogenomics Knowledge Base (www.PharmGKB.org).
Phoebe White, senior director, Taqman genotyping
business, says trying to identify sets of drug
metabolism genes has huge relevance for clinical outcome
studies. The company plans to use the assay in clinical
research and to identify assays with clinical relevance
for ADME-TOX studies.
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