In all of the discussions about driving down the cost of sequencing, I haven't seen much about the cost of nucleotides (or fluorescent nucleotides, for that matter). Genomic target enrichment methods (e.g., Nimblegen arrays) rely on (expensive) synthetic DNA on, or cleaved off of, microarray surfaces. Costs of standard oligos such as universal primers can be amortized over many samples, but as we approach the $1000 or even the $100 genome, costs of nucleotides and enzymes for PCR or phosphoramidites for custom oligo synthesis may become a factor. Is anyone aware of technology that could drive down these costs? Maybe the single molecule sequencing methods like Helicos or DNA nanopores will have a better chance once all of the reagent costs are factored in.
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This falls in line with my own reflections. None of the currently sold new-generation sequencing methods can cope with a sample containing the entire human genome in single run. And there is no need for that because most disease phenotypes correlate with mutations found within exons or in their vicinity, and these account for 1 to 2% human genome or about 60Mb of the total sequence. This is why the enrichment question is in the focus of the current research.
There is an explosive growth in the number of papers addressing the enrichment for exons. I have not read all of them, but those I have invariably use “programmable microarrays” containing many thousands of unique primers. In my childhood I attempted just to count from 1 to 1000 and found it a hard job.
Does anybody know the approximate price of a programmable microarray containing, say, 385,000 tiled oligonucleotides corresponding to 30,000 exons (Hodges et al., et al.,2007, Nat Genet Nov 4: [Epub ahead of print]).
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At some point recently I remember reading that Nimblegen was offering a giveaway of 15 custom arrays to the person/lab who proposed the best experiment. In the contest rules they stated the retail value of that prize to be $18,000US...which translates to ~$1200 per chip.Originally posted by Michael L. Altshuler View PostDoes anybody know the approximate price of a programmable microarray containing, say, 385,000 tiled oligonucleotides corresponding to 30,000 exons (Hodges et al., et al.,2007, Nat Genet Nov 4: [Epub ahead of print]).
Not too bad, and they undoubtedly have at least 50% margin in that cost. So if you're buying in bulk now I'm sure you can get the chip cost well below $1000.
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CRISPR/Cas9 sparked the gene editing revolution for both research and therapeutics.1 But this system still showed severe issues that limited its applications. The most prominent were the heavy reliance on PAM sequences, delivery limitations, double-stranded breaks that prompt unintended edits and cell death, and editing inefficiency (both in targeting and in knock-in reliability).
Despite this, “CRISPR helped turn genome editing from a specialized technique into...-
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