Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood.
We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.
Department of Bioengineering, Stanford University and Howard Hughes Medical Institute, 318 Campus Drive, Clark Center, Room E300, Stanford, CA 94305, USA.
H Christina
HC
Fan
Yair J
YJ
Blumenfeld
Usha
U
Chitkara
Louanne
L
Hudgins
Stephen R
SR
Quake
D000782:Aneuploidy; D001483:Base Sequence; D002474:Cell-Free System; D002877:Chromosomes, Human / Q000235:genetics; D004247:DNA / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009035:Mothers; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014158:Transcription, Genetic / Q000235:genetics
D004247:DNA