Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human fetuses using oligonucleotide microarray analysis of fetal mRNA isolated from amniocytes to investigate the genetic background of the polygenic neural tube defect Spina bifida

ABSTRACT: In polygenic disorders we do not know exactly, how many genes are involved in the pathomechanism, but the analysis of fetal gene expression can get us closer to the solution. In our study we were searching for the genetic background of the polygenic neural tube defect, which is the second most common birth defect in the world (1 in 1000 live births). Our data revealed novel candidate genes, like SLAP, LST1 and BENE, which can play an important role in the pathogenesis of neural tube defects. We created a data warehouse from the results, suitable for further analysis. This study also demonstrates that a routinely collected amount of amniotic fluid (as small as 6 mL) is enough to successfully hybridize isolated RNA to expression arrays, making the ability to use the technique from normally collected amniotic fluid samples. Experiment Overall Design: We report an in vivo study in living human fetuses using oligonucleotide microarray analysis of fetal mRNA isolated from amniocytes, which were collected by amniocentesis. RNA was successfully isolated, amplified, labeled, and hybridized to whole-genome Affymetrix transcript arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Balazs Gyorffy

PROVIDER: E-GEOD-4182 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders.

Nagy Gyula Richárd GR Gyõrffy Balázs B Galamb Orsolya O Molnár Béla B Nagy Bálint B Papp Zoltán Z

Clinical chemistry 20060928 11

<h4>Background</h4>Neural tube defects related to polygenic disorders are the second most common birth defects in the world, but no molecular biologic tests are available to analyze the genes involved in the pathomechanism of these disorders. We explored the use of routinely collected amniotic fluid to characterize the differential gene expression profiles of polygenic disorders.<h4>Methods</h4>We used oligonucleotide microarrays to analyze amniotic fluid samples obtained from pregnant women car ...[more]

PMID: 17008366

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Project description:Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in an inflammatory process, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there is still little knowledge about the functional roles of innate immune cells that respond to invading microbes. In the current study, we performed RNA sequencing of sorted neutrophils and monocytes/macrophages from amniotic fluid from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e. preterm or term delivery). We showed that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection that are indicative of the distinct roles these cells play. We also found that amniotic fluid monocytes/macrophages of fetal origin display impaired ability to clear out microbes invading the amniotic cavity compared to those of maternal origin. Notably, we demonstrate that the transcriptomic changes in amniotic fluid monocytes/macrophages are heavily associated with the severity of the fetal inflammatory response, suggesting that the trafficking of fetal neutrophils throughout the umbilical cord is partially modulated by monocytes/macrophages in the amniotic cavity. Finally, we show that amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptomic activity compared to those from term deliveries, highlighting the protective role of these innate immune cells in this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection, and provide new insights into the functions of amniotic fluid neutrophils and monocytes in the amniotic cavity.

Dataset Information

Transcription profiling of human fetuses using oligonucleotide microarray analysis of fetal mRNA isolated from amniocytes to investigate the genetic background of the polygenic neural tube defect Spina bifida

Publications

Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders.

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