dc.contributor.author | Goldwasser, Jonathan | |
dc.contributor.author | Cohen, Pazit Y. | |
dc.contributor.author | Yang, Eric | |
dc.contributor.author | Balaguer, Patrick | |
dc.contributor.author | Yarmush, Martin L. | |
dc.contributor.author | Nahmias, Yaakov | |
dc.date.accessioned | 2010-12-22T19:15:58Z | |
dc.date.available | 2010-12-22T19:15:58Z | |
dc.date.issued | 2010-08 | |
dc.date.submitted | 2010-03 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/60364 | |
dc.description.abstract | Background
Screening tests for Trisomy 21 (T21), also known as Down syndrome, are routinely performed for the majority of pregnant women. However, current tests rely on either evaluating non-specific markers, which lead to false negative and false positive results, or on invasive tests, which while highly accurate, are expensive and carry a risk of fetal loss. We outline a novel, rapid, highly sensitive, and targeted approach to non-invasively detect fetal T21 using maternal plasma DNA.
Methods and Findings
Highly heterozygous tandem Single Nucleotide Polymorphism (SNP) sequences on chromosome 21 were analyzed using High-Fidelity PCR and Cycling Temperature Capillary Electrophoresis (CTCE). This approach was used to blindly analyze plasma DNA obtained from peripheral blood from 40 high risk pregnant women, in adherence to a Medical College of Wisconsin Institutional Review Board approved protocol. Tandem SNP sequences were informative when the mother was heterozygous and a third paternal haplotype was present, permitting a quantitative comparison between the maternally inherited haplotype and the paternally inherited haplotype to infer fetal chromosomal dosage by calculating a Haplotype Ratio (HR). 27 subjects were assessable; 13 subjects were not informative due to either low DNA yield or were not informative at the tandem SNP sequences examined. All results were confirmed by a procedure (amniocentesis/CVS) or at postnatal follow-up. Twenty subjects were identified as carrying a disomy 21 fetus (with two copies of chromosome 21) and seven subjects were identified as carrying a T21 fetus. The sensitivity and the specificity of the assay was 100% when HR values lying between 3/5 and 5/3 were used as a threshold for normal subjects.
Conclusions
In summary, a targeted approach, based on calculation of Haplotype Ratios from tandem SNP sequences combined with a sensitive and quantitative DNA measurement technology can be used to accurately detect fetal T21 in maternal plasma when sufficient fetal DNA is present in maternal plasma. | en_US |
dc.description.sponsorship | Medical College of Wisconsin. Dept. of Surgery | en_US |
dc.description.sponsorship | Medical College of Wisconsin. Biotechnology and Bioengineering Center (Inducement Grant Fund) | en_US |
dc.description.sponsorship | Wallace H. Coulter Foundation | en_US |
dc.description.sponsorship | Tandem Diagnostics (Firm) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (NSF#0438604 ) | en_US |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pone.0012399 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en_US |
dc.source | PLoS | en_US |
dc.title | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Goldwasser, Jonathan et al. “Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPARα, PPARγ and LXRα.” PLoS ONE 5.8 (2010): e12399. | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.approver | Goldwasser, Jonathan | |
dc.contributor.mitauthor | Goldwasser, Jonathan | |
dc.relation.journal | PLoS ONE | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Goldwasser, Jonathan; Cohen, Pazit Y.; Yang, Eric; Balaguer, Patrick; Yarmush, Martin L.; Nahmias, Yaakov | en |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |