ࡱ> oqna jbjb11 [[ .......~FFFF R ~jjjjjKKK+------,jR Y.K)"KKKY+..jjn+++K.j.j++B$f....K+++..+^ F:++0+D +D ++.~~B~~BGenomics Paper Jon Dozier Reference: Fan, H., and Quake S. Dectection of Aneuploidy with Digital Polyermerase Chain Reaction Analytical Chemistry, 2007, 79, 7576-7579. Bioanalysis and Sample: In this paper, the author show how digital-PCR (d-PCR), which is used to quantify the amount DNA in sample by counting the amplifications from single molecules, can be used diagnose aneuploidy which is a change in the number of chromosomes. The researchers used this technique to analyze two samples, one genomic sample from a normal cell line and one genomic sample from a trisomy 21, commonly known as Down Syndrome, cell line. They also looked if this technique could be used to detect aneuploidy in samples that had a mixture of regular DNA and aneuploidy DNA, and down to what level they could detect an aneuploidy sample. Importance: Detection of aneuplody is one most common pre-natal diagnostic screens, however, current screening practices take awhile to get the results; in most cases two weeks which can leave would be parents fretting. With this new method the time that a screen takes could be reduced to two hours. Also unlike with other PCR methods, like RT-PCR or Q-PCR, this method could not only detect allelic variation within cells but also detect aneuploidy, which is simply a difference in the amount chromosomal material. Technique: The d-PCR technique that the authors use requires first the sample be diluted to a low concentration. This solution is than pipetted into nanoliter wells on a specially fabricated chip. The concentration is such that on average there is less than one copy of DNA per well. After the PCR reaction is run Taqman probes that hydrize to either the DNA sample of interest, in this case chromosome 21, or a refernce pieces of DNA, in this case the for the gene GAPDH which is located on chromosome 12. The number of positive signals, which is measured by the number wells that fluoresce, correlates to the number of molecules in the original samples. By comparing the number of hits for the chromosome 21 DNA to a standard GAPDH gene, the authors could detect whether or not the sample contained an aneuploidy. For a normal sample the ratio should be 1:1 but for a trisomy 21 sample the ratio is 3:2. Also based upon their technique the authors found that they could detect an aneuploidy specimen that contained only 10% aneuploidy DNA, and this would require only 4000 molecules of DNA.  Example: Figure A shows two chips with two samples, both normal and trisomy 21 amplified for aneuploidy DNA, and figure B shows two chips with the same two samples amplified for GAPDH. Opinion: I think that the method the authors developed shows a lot of promise for aneuploidy detection in a clinically setting. I was also surprised by the low limit of detection, which only require a couple thousand DNA molecules. 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