UNASSIGNED: Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of @entity2007 and become increasingly accepted in clinical practice. We investigated whether NIPT using @entity5599 ( @entity5599 ) could reliably detect subchromosomal deletions/duplications in @entity1 carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant @entity1 to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant @entity1 with @entity2241 detected on ultrasound who also underwent an invasive diagnostic procedure. We used @entity5599 of maternal plasma DNA to detect @entity854 and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, @entity5599 detected 56 of 78 (71.8%) @entity854 detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude @entity3203 . This study shows that detection of fetal @entity854 is a viable extension of NIPT based on @entity5599 . Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating @entity5 DNA for detection of @entity5 .

Noninvasive detection of fetal XXXX by semiconductor sequencing of maternal plasma DNA.

@entity1 :: ('9606', 'Species') :: ['women'] @entity2007 :: ('MESH:D000782', 'Disease') :: ['aneuploidy'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity5599 :: ('MESH:D010855', 'Disease') :: ['semiconductor sequencing platform', 'SSP'] @entity854 :: ('MESH:D018376', 'Disease') :: ['subchromosomal abnormalities'] @entity3203 :: ('MESH:D059786', 'Disease') :: ['maternal karyotype abnormalities'] @entity2241 :: ('MESH:D005315', 'Disease') :: ['fetal structural abnormalities']
@entity854 :: (MESH:D018376,Disease) :: ['subchromosomal abnormalities']
