Many many years ago I started up an Affymetrix microarray core lab. One of the early presentations on the 10k genotyping arrays was an epiphany for me. It was clear from the data that copy number would be easily discernible from the technology. I also thought that 10â€™s of thousands of genotypes, with the possibility of millions to come would allow strong phenotype:genotype correlations to be made. In fact I went to our TechTransfer department with the idea of developing a photofit chip but the idea was discounted as just too difficult with this new and unproven technology. Things don’t stand still in Genomics though.
Biotechnology holds the key: In this monthâ€™s Nature Biotechnology Caitlin Smith, Stephen Strauss and Laura DeFrancesco published a very interesting feature article on the use of DNA in forensics. All the ideas from ten years ago came back including one that I have been uncomfortable talking about since it occurred to me (see Dr Evilâ€™s DNA Disguise down the page).
The authors give a very good review of current DNA technology for use in forensics. STR profiles have been used for more than twenty years and recent work showed they could be profiled using NGS, the authors missed this reference and I think it is a key one on the road to NGS tests as it provides a potential stepping stone. (see Short-read,high-throughput sequencing technology for STR genotyping). The next big step is likely to come from NGS-genotyping of 1000â€™s or more SNPs. The article mentions two interesting uses of SNPs, HIrisPLEX, which uses six genes to determine blue or brown eye colour and hair color; and the Identitas SNP-chip for profiling ethnicity, gender, relatedness, geographic ancestry and other phenotypic traits (although their website is woefully lacking on details).
STRs can work on vanishingly small amounts of DNA but Michael Fischerâ€™s group at the Oxford Systems Biology Institute published a method in Genome Research last year for NGS library prep from 20pg of MouseDNA. It should be possible to amplify or select 1000â€™s of SNPS from these libraries to run a cheap benchtop sequencer analysis.
It looks to me that the days of STR analysis are numbered.
Facebook photofit app: Eric Lander was on a panel discussion at AGBT a few years ago organised by PacBio. He was taking part in a debate on the public release of genome data and said that his daughter (17 at the time) was happy to splash her life over Facebook and may be much less concerned about sharing her genomic data than her father might. If we can buy a 23andMe test for as little as $99, or a genome for $1000 is there a market for a Facebook app that sends you updates on research findings?
And if people put this kind of data if Facebook with its powerful feature recognition tools could we create a photofit app? This is not as crazy as it sounded to the people sat on the same table as me at that dinner! With millions of possible customers and links to friends and family already in the system, FaceBook seems like the next big step for 23andME or DNAncestry and others like them. It wonâ€™t take the FBI long to realise how useful the data are. Although the US has somewhat tighter control on this kind of data than the UK, and I thought we were not yet a police state!
Dr Evilâ€™s DNA disguise: This is the idea Iâ€™ve had floating around for more than a decade. Iâ€™ve been nervous about writing or discussing it as the idea is such a simple one Iâ€™d worried that someone might actually use it and there could be some comeback on me. Fortunately the authors of the Nature Biotechnology article have out the idea out there so here I go…
Itâ€™s quite simple really. PCR amplify an STR profile from someone unrelated to you and dilute it into a spray bottle. A quick squirt as you are burgling a house and tracking you down as a suspect in a case becomes more difficult. The DNA disguise will massively out compete the small amount of DNA in your fingerprint in the forensic test.
And if you are concerned that SNPs might take over as the default forensic test then why not make a Nextera library. It only cost $60 to make and again PCR amplification will drown out any signal from your own DNA. A side-box in the article mentions work by Nucleix that demonstrates that you can distinguish native DNA by looking at methylation so the disguise may not be perfect.
I will now not only smell nicer during my next seminar, but will also be almost undetectable in a crime scene with my new DNAftershave.
PS: DNAftershave is now available on eBay (with profits going to charity).
PPS: If you drank a PCR reaction would it be detectable as circulating DNA or in urine? Or would it simply be degraded in your stomach?