We have done a whole exome scan for US $650 at 65x coverage and are very pleased with the information we received from the scan.
The 23andme scan is mostly reporting markers that are fairly common: the exome scan tells you about things that are very specific to you
and your family. The scan revealed some very interesting leads, many of these leads were things we had never heard of before. The illnesses related to them do not have proper names, instead they usually refer to obscure enzyme deficiencies etc. that most doctors would not be familiar with.
Here are some suggestions, if others are also interested in having an exome scan.
Don't wait! Scan your Exome Now!
The exome scan revealed a wealth of information. The scan came back with multiple BRCA mutations and many, many other interesting results. At this time, exome scans are still not quite ready for full roll-out, though even now the companies are gearing up for the massive wave of demand that is quickly approaching. When the price moves down some more, the genomics analysis software is improved, and the exome sequencing technology is fine tuned, then exome scans will obviously be done routinely.
With 23andme, all your genotypes that match the reference genome are reported. These reference results are mostly not significant.
(In the exome scan, many times the reference result was the variant! The reference should be redefined as the major allele.)
With the exome, only your genotypes that do not match the reference genome are reported. So in the exome scan we received, of the 62 million loci sequenced, only 60,000 were reported as different from the reference. One problem was that of these 60,000; 20,000 were considered to be low quality reads (probably errors). [The exome scan was highly enriched in the errors from 62 million base pairs of sequence.] However, quality scores for each base pair was included with the scan. Some of the results within the supposed errors were alarming, including pathogenic mutations in the APP gene.
Ask the company doing the scan, if it would be possible to enrich the sequencing in disease genes that you are especially interested in.
Also, ask if the mitochondrial exome DNA could be sequenced.
Make sure that you pay extra for more coverage.
We originally ordered a 30x coverage exome scan, though when we realized how inexpensive extra coverage was we moved it up to 65x coverage. A clinical grade exome scan is considered to be 70x coverage. It is worth the extra money. After the fixed costs of getting the scan started have been paid, the marginal cost for another 10x is very reasonable (~US$50).
Be aware that you will be somewhat ripped off. One gigabit of sequence (based on the full genome price) should only cost $10.
Our exome scan would have only cost $80 at that price point. The companies doing the exome scans are making quite a bit of money.
If the regulatory and legal environment were more clearly defined, then the price would likely move down.
The company that did the exome scan cut a few corners with the scan. The technology used in the exome scan, sequenced base pairs in 100 long reads. When the exon was 200 to 300 base pairs long, it was necessary to have a big pile up at centre of the exon, However, often when the exon was longer than 300 base pairs, the scan scrimped on both ends. The centre of the exon could have over 200 reads while the ends often had long tails of less than 5 reads or none at all. It might be good to determine whether it could be specified
what the minimum read depth of the tails would be. The 200 reads at the centre of the exons really did not, at the margin, contribute substantial data.
Make a Contribution
From the exome scan, over 500 of the SNV variants, 200 of the insertions, and 300 of the deletions (which were all read at high quality) were not found in dbSNP. These are still early days in genomics, though it should be realized that the ordinary citizen can make a relevant
contribution in moving genomics forward by having their exome scanned. The value of genome scanning is tremendously enhanced when the overall genomic dataset is expanded. There were thousands of variants in the exome scan that reported back as very rare, though the medical implications are not known. Establishing which variants in an exome actually contribute to pathology will allow exome scans to provide invaluable medical information.
By having an exome scan done, you can help grow the dataset and make a contribution.