Browsing by Author "Nõukas, Margit"

Now showing 1 - 2 of 2

C14orf132 gene is possibly related to extremely low birth weight
(2016-09) Tiirats, Airi; Viltrop, Triin; Nõukas, Margit; Reimann, Ene; Salumets, Andres; Kõks, Sulev
Background Despite extensive research the genetic component of extremely low birth weight (ELBW) in newborns has remained obscure. Results The aim of the case study was to identify candidate gene(s) causing ELBW in newborns and hypotrophy in infants. A family of four was studied: mother, father and two ELBW-phenotype children. Studies were made of the medical conditions of the second child at birth and post-partum - peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy and suspected metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate the genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 (chromosome 14 open reading frame 132) differentially expressed, with the level of the transcript significantly lower in the blood samples of the children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion We demonstrated the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the pre- and early postnatal developmental delay through the altered gene expression.
In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages
(Nature Medicine, 2019-11-04) Esteki, Masoud Zamani; Viltrop, Triin; Tšuiko, Olga; Tiirats, Airi; Koel, Mariann; Nõukas, Margit; Žilina, Olga; Teearu, Katre; Marjonen, Heidi; Kahila, Hanna; Meekels, Jeroen; Söderström-Anttila, Viveca; Suikkari, Anne-Maria; Tiitinen, Aila; Mägi, Reedik; Kõks, Sulev; Kaminen-Ahola, Nina; Kurg, Ants; Voet, Thierry; Vermeesch, Joris Robert; Salumets, Andres
Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1,2,3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.