Fan et al.

"Shotgun DNA sequencing" assay for human chromosomal trisomies

     DNA from cells shed by a fetus in utero can be collected from the circulating blood of the pregnant women.  In a clinical application of Next-Generation DNA sequencing (NGS) technology, the DNA is randomly amplified by PCR ("shotgunned") as millions of short sequences. A 25bp sequence EST "tag" can be read from one end of each of these fragments ("Expressed Sequence Tag"). Based on knowledge of the complete human genome sequence gained from the Human Genome Project, each tag can be "assigned" automatically by computer to a particular chromosome. 

    The three most common trisomies in newborn humans are those of chromosomes 13 (Patau Syndrome),
18 (Edward Syndrome), and 21 (Down Syndrome). The main graph shows that the presence of these trisomies in an early fetus increases the number of tag assignments that map to that chromosome, as compared with to an unaffected
(disomic) fetus, because there is an extra chromosome in each case. 

   For nine pregnancies involving fetuses with Trisomy 21 (red circles),  the expanded graph on the right shows significantly more tag assignments than do any of the unaffected disomy 21 pregnancies (blue triangles) or (control, non-pregnant) adult males (black squares).

Figure after Fan et al. 2008 Proc Natl Acad Sci 105,16266; All text material © 2014 by Steven M. Carr