title: Copy number variation profile in the placental and parental genomes of recurrent pregnancy loss families.
abstract: We have previously shown an extensive load of somatic copy number variations (CNVs) in the human placental genome with the highest fraction detected in normal term pregnancies. Hereby, we hypothesized that insufficient promotion of CNVs may impair placental development and lead to recurrent pregnancy loss (RPL). RPL affects ~3% of couples aiming at childbirth and idiopathic RPL represents ~50% of cases. We analysed placental and parental CNV profiles of idiopathic RPL trios (mother-father-placenta) and duos (mother-placenta). Consistent with the hypothesis, the placental genomes of RPL cases exhibited 2-fold less CNVs compared to uncomplicated 1sttrimester pregnancies (P = 0.02). This difference mainly arose from lower number of duplications. Overall, 1sttrimester control placentas shared only 5.3% of identified CNV regions with RPL cases, whereas the respective fraction with term placentas was 35.1% (P = 1.1 × 10-9). Disruption of the genes NUP98 (embryonic stem cell development) and MTRR (folate metabolism) was detected exclusively in RPL placentas, potentially indicative to novel loci implicated in RPL. Interestingly, genes with higher overall expression were prone to deletions (>3-fold higher median expression compared to genes unaffected by CNVs, P = 6.69 × 10-20). Additionally, large pericentromeric and subtelomeric CNVs in parental genomes emerged as a risk factor for RPL.
authors.affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Riia 23 St., Tartu 51010, Estonia.
authors.forename: Laura
authors.initials: L
authors.lastname: Kasak
authors.affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Riia 23 St., Tartu 51010, Estonia.|Department of Obstetrics and Gynaecology, University of Tartu, Puusepa St. 8, Tartu 51014, Estonia.|Women's Clinic of Tartu University Hospital, Puusepa St. 8, Tartu 51014, Estonia.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Rull
authors.affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Riia 23 St., Tartu 51010, Estonia.|Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila St. 19, Tartu 51014, Estonia.
authors.forename: Siim
authors.initials: S
authors.lastname: Sõber
authors.affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Riia 23 St., Tartu 51010, Estonia.|Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila St. 19, Tartu 51014, Estonia.
authors.forename: Maris
authors.initials: M
authors.lastname: Laan
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics; D055815:Young Adult