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 whole-genome 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. CONCLUSIONS: This pilot study demonstrated that a routinely collected amount of amniotic fluid (as small as 6 mL) can provide sufficient RNA to successfully hybridize to expression arrays. Analysis of the differences in fetal gene expressions might help us decipher the complex genetic background of polygenic disorders.
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 whole-genome 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. CONCLUSIONS: This pilot study demonstrated that a routinely collected amount of amniotic fluid (as small as 6 mL) can provide sufficient RNA to successfully hybridize to expression arrays. Analysis of the differences in fetal gene expressions might help us decipher the complex genetic background of polygenic disorders.
Authors: M Scott-Finley; J G Woo; M Habli; O Ramos-Gonzales; J F Cnota; Y Wang; B D Kamath-Rayne; A C Hinton; W J Polzin; T M Crombleholme; R B Hinton Journal: J Perinatol Date: 2015-04-30 Impact factor: 2.521
Authors: Zhongzhong Chen; Yunping Lei; Yufang Zheng; Vanessa Aguiar-Pulido; M Elizabeth Ross; Rui Peng; Li Jin; Ting Zhang; Richard H Finnell; Hongyan Wang Journal: Cell Res Date: 2018-07-05 Impact factor: 25.617
Authors: Vanessa Aguiar-Pulido; Paul Wolujewicz; Alexander Martinez-Fundichely; Eran Elhaik; Gaurav Thareja; Alice Abdel Aleem; Nader Chalhoub; Tawny Cuykendall; Jamel Al-Zamer; Yunping Lei; Haitham El-Bashir; James M Musser; Abdulla Al-Kaabi; Gary M Shaw; Ekta Khurana; Karsten Suhre; Christopher E Mason; Olivier Elemento; Richard H Finnell; M Elizabeth Ross Journal: Proc Natl Acad Sci U S A Date: 2021-12-21 Impact factor: 11.205
Authors: Christian Schiller; Carina Nowak; Kalliope N Diakopoulos; Ulrich H Weidle; Elisabeth H Weiss Journal: PLoS One Date: 2014-05-09 Impact factor: 3.240