Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha
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 whi...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2010
|
| Online Access: | http://hdl.handle.net/1721.1/60364 |
| _version_ | 1826216154649067520 |
|---|---|
| author | Goldwasser, Jonathan Cohen, Pazit Y. Yang, Eric Balaguer, Patrick Yarmush, Martin L. Nahmias, Yaakov |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Goldwasser, Jonathan Cohen, Pazit Y. Yang, Eric Balaguer, Patrick Yarmush, Martin L. Nahmias, Yaakov |
| author_sort | Goldwasser, Jonathan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:42:49Z |
| format | Article |
| id | mit-1721.1/60364 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:42:49Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/603642022-10-03T07:45:43Z Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha Goldwasser, Jonathan Cohen, Pazit Y. Yang, Eric Balaguer, Patrick Yarmush, Martin L. Nahmias, Yaakov Harvard University--MIT Division of Health Sciences and Technology Goldwasser, Jonathan Goldwasser, Jonathan 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. Medical College of Wisconsin. Dept. of Surgery Medical College of Wisconsin. Biotechnology and Bioengineering Center (Inducement Grant Fund) Wallace H. Coulter Foundation Tandem Diagnostics (Firm) National Science Foundation (U.S.) (NSF#0438604 ) 2010-12-22T19:15:58Z 2010-12-22T19:15:58Z 2010-08 2010-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/60364 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 http://dx.doi.org/10.1371/journal.pone.0012399 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Goldwasser, Jonathan Cohen, Pazit Y. Yang, Eric Balaguer, Patrick Yarmush, Martin L. Nahmias, Yaakov Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title_full | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title_fullStr | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title_full_unstemmed | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title_short | Transcriptional Regulation of Human and Rat Hepatic Lipid Metabolism by the Grapefruit Flavonoid Naringenin: Role of PPAR alpha, PPAR gamma and LXR alpha |
| title_sort | transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin role of ppar alpha ppar gamma and lxr alpha |
| url | http://hdl.handle.net/1721.1/60364 |
| work_keys_str_mv | AT goldwasserjonathan transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha AT cohenpazity transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha AT yangeric transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha AT balaguerpatrick transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha AT yarmushmartinl transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha AT nahmiasyaakov transcriptionalregulationofhumanandrathepaticlipidmetabolismbythegrapefruitflavonoidnaringeninroleofpparalphappargammaandlxralpha |