I will focus on the genetic analysis and diagnostics company Sequenom in this blog. Sequenom plays in the same space as Illumina, Applied Biosciences and Beckman Coulter (Affymetrix does not have a directly competing product). 

Sequenom's main product is MassARRAY which is a mass spectrometer based genetic analyzer. MassARRAY's core application is SNP genotyping which is based on single base primer extension method and depends on the mass difference between bases to make a call for an SNP. The company refers to this application as "iPLEX genotyping", emphasizing the method's multiplexed use to analyze up to 40 SNPs in one individual reaction. They market this product toward "fine mapping" studies  which need a small number of SNPs (typically <100) with higher sample throughput  instead of the genome wide scans  that analyze a large number of SNPs (1,000-10,000) but with much lower sample throughput rate (<50 samples/day).

The MassARRAY instrument can also be used for a variety of application including quantitate gene expression, epigenetic analysis, and the recently announced iSEQ for molecular typing of microorganisms.

The reason I chose Sequenom as my first company for this blog is not just MassARRAY but its noninvasive prenatal diagnostic technology (NIPD) for down syndrome testing.

The company's NIPD Technology is based on the work of Professor Dennis Lo at Chinese Hong Kong University, and isolates and analyzes circulating fetal nucleic acid from the maternal blood sample. The method is both non-invasive, therefore poses no risk to the baby, and has the possibility to be performed earlier in the pregnancy. The alternative is amniocentesis which involves the insertion of a needle through the womb to sample the amniotic fluid that bathes the fetus. Amniocentesis carries a 0.5-2% chance of miscarriage. 

In a pivotal research study published in February 2007 Nature Medicine, Dr. Dennis Lo’s group studied the PLAC4 (placenta specific 4) gene for detection of Down Syndrome. PLAC4 is the most suitable because it is located on chromosome 21 and its expression is restricted to the placenta, which allows fetus-specific analysis without any interference from maternal genome. The group made use of its expertise with mass spectrometry to quantify chromosome 21 levels. They used SNPs located in the fetal-specific gene. In case of normal fetus, the sample contains equal ratios of each SNP allele (1:1 ratio) If, however, a trisomy is present, the allele ratio shifts to 2:1 leading to a diagnosis of Down syndrome.

Sequenom's down syndrome prenatal diagnostic test is in developmental stages and the recently announced data seems very promising. On 4th June, the company reported that in blinded studies involving approximately 200 clinical samples collected both prospectively and retrospectively, its proprietary test for Down syndrome correctly identified 100% of all Down syndrome samples (i.e. sensitivity or detection rate), without any false-positive outcomes (i.e. 100% specificity). (see this post in the diagnostics category)

Here is the video overview of Sequenom's down syndrome test: