What are microsatellites?
Microsatellites, or repetitive DNA, defined as tandem repeats of 1- to 6-mer motifs, are pervasive throughout the human genome in both coding and non-coding regions. An example is the DNA sequence, CAGCAGCAGCAGCAG, where the motif (CAG) is repeated 5 times. There are approximately one million such repeat-containing loci in the human genome. Microsatellites are mostly known for their role in forensics and paternity testing. About 20 microsatellite loci, which are known to vary among individuals, are measured for all forensics and paternity testing. Orbit Genomics™ explores all one million microsatellite loci in the genome.
How are they different from other DNA sequence variations in the human genome?
Most of the genome is non-repeating, and the majority of genetic and genomic studies have focused on Single Nucleotide Polymorphisms, called SNPs. These variants, where a single DNA base (or nucleotide) changes, for example a G to an A, are often studied for their role in disease. Although they have been studied extensively, they fall far short of explaining the known or suspected genetic components of disease, especially complex diseases such as cancer, heart or neurological diseases. Over 50 hereditary cancer syndromes have been identified; yet, inherited mutations only account for 5-10% of all cancers.
Because of their repeating nature, microsatellites tend to be more susceptible to unstable genomic processes. They are more sensitive to cellular stressors and mutate ten thousand times faster than SNPs and other genetic mutations. In addition, microsatellite mutations are reversible. As a result, microsatellites are excellent readouts of genome stability and they reflect both inherited and acquired disease risk. Standard sequencing algorithms are optimized for SNP detection and do not correctly analyze microsatellites, making them more difficult to study.
How does Orbit Genomics use microsatellites?
Orbit Genomics has developed technologies to accurately measure microsatellite variations and associate those variations with disease. This technology is based on 20 years of research resulting in over 35 scientific published studies co-authored by our CSO, Skip Garner. Orbit Genomics’ OrbiSeq™ technology platform uses proprietary algorithms to accurately call the one million microsatellite loci in the human genome. These advancements have enabled us to develop new diagnostic tools to evaluate risk of certain cancers and for actionable clinical decision support. Orbit Genomics’ analysis pipelines have re-assembled thousands of disease and non-disease (control) genomes to accurately discover small subsets of variants at microsatellite loci, which together form a diagnostic test. Orbit Genomics has also used this technique to compare different traits in responders and non-responders to a given therapy to develop companion diagnostics for new or established drugs.
The OrbiSeq™ technology platform is applicable to many diseases and conditions beyond cancer. Because microsatellites reflect overall genome stability and mutate rapidly, they are an ideal marker for diseases and conditions of the aged. The company has already demonstrated the ability to measure a person’s genetic age and has identified microsatellite loci specific to many other diseases and conditions beyond cancer.