Use of Routinely Collected Amniotic Fluid for Whole-Genome Expression Analysis of Polygenic Disorders

Abstract

Background: 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. Methods: We used oligonucleotide microarrays to analyze amniotic fluid samples obtained from pregnant women carrying fetuses with neural tube defects diagnosed during ultrasound examination. The control samples were obtained from pregnant women who underwent routine genetic amniocentesis because of advanced maternal age (>35 years). We also investigated specific folate-related genes because maternal periconceptional folic acid supplementation has been found to have a protective effect with respect to neural tube defects. Results: Fetal mRNA from amniocytes was successfully isolated, amplified, labeled, and hybridized to wholegenome transcript arrays. We detected differential gene expression profiles between cases and controls. Highlighted genes such as SLA, LST1, and BENE might be important in the development of neural tube defects. None of the specific folate-related genes were in the top 100 associated transcripts.

Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth

“…For example, gene expression studies may accelerate our understanding of mechanism. 32 The role of leptin in placental and fetal growth and the potential utility of AFL in pregnancy management are promising and require further study. In summary, these results are important in assessing the impact of AFL levels to maternal and fetal health outcomes.…”

Rat Monoclonal Antibodies Specific for LST1 Proteins

“…Recent work has also shown that high LST1 expression levels are associated with several inflammatory diseases including rheumatoid arthritis (4) and the inflammatory response believed to cause neural tube defect. (8) These associations, however, have been established based on mRNA expression data and have not been validated at the protein level. To allow insights into the structure and function of LST1 isoforms and to discern their potential role in autoimmune diseases, we generated and characterized rat monoclonal antibodies specific for LST1.…”

An Upstream Open Reading Frame Regulates LST1 Expression during Monocyte Differentiation

“…Additionally, we have recently found transmembrane LST1 to regulate cell-cell communication [12]. Several studies have proposed that LST1 may play a role in inflammatory diseases including Reactive Arthritis [13], Lupus Nephritis [14] and the inflammatory response believed to cause Neural Tube Defect [15]. These studies correlated high levels of LST1 expression with inflammatory pathologies, thereby further substantiating a potential link between LST1 protein levels and inflammation.…”