BioArray News (subscription required) reports that genomic analysis technology provider Illumina has launched a new family of genotyping chips designed to simultaneously assay 4 million sites of variation in the human genome.
The chips are a major step up from the 1-million-feature chips that
currently represent the state of the art, and take advantage of several
public projects generating catalogues of human genetic variation (such
as the 1000 Genomes Project).
Illumina has also increased the density of markers in and around genes,
and fleshed out regions that have previously been associated with
complex traits and diseases.
The new chips are specifically designed to increase the coverage of two
types of variants that tended to be poorly captured by previous
generations of chips: rare variants, and structural variation.
Chip-based genotyping is very much a place-holder technology while we
wait for whole-genome sequencing to become cheap and accurate enough to
use for large-scale studies. Illumina clearly expects the market to
persist for at least another couple of years before sequencing takes
There might be some customers who will hold off for the next generation
of arrays. “We think it will be a year to a year and a half until all
the content is out there and we arrive at a penultimate array that has
the content that everyone will want,” [Illumina CEO Jay Flatley] said.
Of course, Illumina is well-placed to ride the wave regardless of when
the sequencing transition occurs; in addition to its genotyping
products it provides the most successful current second-generation
sequencing technology, the Genome Analyzer, and has secured an exclusive marketing contract for one of the most promising third-generation platforms, Oxford Nanopore.
Bigger is not always better
The BioArray News article also notes that the most recent generation of genotyping chips (the 1M series, with one million features) have “not seen adoption … to the extent of other chips”. There’s a good reason for that, which is spelled out in an article in PLoS Genetics this week: despite the increased number of variants on the 1M chip, its value for money (in terms of power for a fixed study cost) is actually lower than earlier-generation chips.
Here’s a table from that paper illustrating this point:
The table assumes a fixed budget of $2 million for genotyping. Despite having nearly twice the number of markers, the Illumina 1M chip actually has substantially lower power than the earlier-generation 610K chip, for a simple reason: because the 1M chip is almost twice as expensive, researchers have to settle for genotyping many fewer individuals; and the increased power from adding more markers doesn’t make up for this drop in sample size.
The same economics may well apply to the new chips (depending on their pricing, of course). The addition of rare variants to the chip adds an extra element to the equation; but it should be noted that the low power of genotyping studies to detect rare disease-causing variants means that such studies will require very large sample sizes; if the new chips are too expensive such studies may well be impractical for most research groups, encouraging them to lean towards targeted resequencing of candidate genes instead.