Review
Biochemistry & Molecular Biology
Osamu Samura, Yoshiharu Nakaoka, Norio Miharu
Summary: Gametogenesis differs between oocytes and sperm, with oocytes having chromosomal aneuploidies and most structural anomalies originating from sperm. Increasing female age leads to an increased number of chromosomal aberrations due to a prolonged meiotic period. Chromosome analysis of sperm is challenging but methods have been developed, allowing for the evaluation of individual sperm. Understanding gametic chromosomal abnormalities is crucial in assisted reproductive technology, but questions regarding which cases should undergo sperm chromosome analysis and result interpretation need to be addressed.
Article
Multidisciplinary Sciences
Siyuan Liu, Nirmala Akula, Paul K. Reardon, Jill Russ, Erin Torres, Liv S. Clasen, Jonathan Blumenthal, Francois Lalonde, Francis J. McMahon, Francis Szele, Christine M. Disteche, M. Zameel Cader, Armin Raznahan
Summary: This study investigates the effects of X, Y, and 21 aneuploidies on gene expression in lymphoblastoid cell lines, fibroblasts, and iPSC-derived neuronal cells. It confirms theoretical models of sex chromosome dosages sensitivity and identifies a set of 41 genes that show obligate dosage sensitivity. The study finds that cis effects of sex chromosome dosages are preserved in different cell types, while trans effects are mostly not preserved.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Filomena Mottola, Marianna Santonastaso, Valentina Ronga, Renata Finelli, Lucia Rocco
Summary: This study investigated the association between polymorphic rearrangements of chromosome 9 and male infertility. The results suggested that these rearrangements might be associated with abnormalities in sperm quality, indicating their potential impact on spermatogenesis regulation.
Article
Neurosciences
Elisa Guma, Antoine Beauchamp, Siyuan Liu, Elizabeth Levitis, Liv S. Clasen, Erin Torres, Jonathan Blumenthal, Francois Lalonde, Lily R. Qiu, Haley Hrncir, Allan MacKenzie-Graham, Xia Yang, Arthur P. Arnold, Jason P. Lerch, Armin Raznahan
Summary: All eutherian mammals exhibit chromosomal sex determination, with contrasting sex chromosome dosages (SCDs) in males (XY) and females (XX). Although direct effects of SCD on regional brain anatomy have been observed in transgenic mice and humans with sex chromosome trisomy (SCT), the cross-species conservation of these effects remains to be tested. We developed a harmonized framework for comparative structural neuroimaging and applied it to study the effects of SCT on regional brain anatomy in both humans and mice. Our findings suggest limited conservation of SCT effects between species, but identify specific brain regions that show overlapping effects of SCT, highlighting targets for future research.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Obstetrics & Gynecology
Line Elmerdahl Frederiksen, Sofie Moller Olgaard, Laura Roos, Olav Bjorn Petersen, Line Rode, Tanja Hartwig, Charlotte Kvist Ekelund, Ida Vogel
Summary: In this register-based study in Denmark, the associations between maternal age and the risk of fetal aneuploidies were assessed. It was found that advanced maternal age is associated with a higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2023)
Article
Biochemistry & Molecular Biology
My Anh Truong, Paula Cane-Gasull, Sippe G. de Vries, Wilco Nijenhuis, Rene Wardenaar, Lukas C. Kapitein, Floris Foijer, Susanne M. A. Lens
Summary: Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve.
Article
Cell Biology
Anna Kouznetsova, Jian Guo Liu, Sonata Valentiniene, Hjalmar Brismar, Christer Hoog
Summary: Aging significantly impacts the chromosome segregation process in human oocytes, leading to aneuploidy, infertility, and developmental disorders. As age increases, the likelihood of chromosome segregation irregularities also increases, resulting in a higher incidence of aneuploidy.
Article
Genetics & Heredity
Casey O. DuBose, John R. Daum, Christopher L. Sansam, Gary J. Gorbsky
Summary: Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine, but genetic aberrations may occur during culture. In this study, two iPSC lines were periodically analyzed using advanced optical mapping, revealing the rapid increase of trisomic cells for chromosome 12 in one cell line. The analysis also identified numerous structural variations distinct from those found in the general population.
Article
Multidisciplinary Sciences
Sunyoung Hwang, Paola Cavaliere, Rui Li, Lihua Julie Zhu, Noah Dephoure, Eduardo M. Torres
Summary: The study reveals that mRNA and protein levels are increased by 1.5-fold on average in trisomy 21 cells, with some proteins enriched for subunits of macromolecular complexes showing signs of post-transcriptional regulation. Additionally, trisomy 21 cells exhibit lower viability and increased dependency on serine-driven lipid synthesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Weber Beringui Feitosa, Patricia L. Morris
Summary: Mammalian oocytes undergo morphological, structural, and molecular changes during a process called oocyte aging. The SUMO pathway, specifically SUMO-2/3 and the SUMO-specific protease SENP-2, are involved in spindle morphology changes and chromosome movements during oocyte aging. Decreased UBC9 and differential ubiquitination patterns also correlate with in vitro oocyte aging. These findings suggest that age-related changes in SUMOylation and the deSUMOylation of key target proteins may contribute to spindle and chromosome alignment defects during mammalian oocyte postovulatory aging, with implications for ART-related human oocyte aging and fertilization success.
Editorial Material
Biochemistry & Molecular Biology
Gian Paolo Tonini
Summary: Neuroblastoma is a pediatric cancer that can present as localized or metastatic disease. Patients with localized tumors tend to have better outcomes, possibly due to lower levels of chromosome instability (CIN), compared to patients with metastatic tumors.
Article
Environmental Sciences
Steen K. T. Ooi, Hui Jiang, Yanyuan Kang, Patrick Allard
Summary: This study found that exposure to low levels of BPA affects early germ cell differentiation in mice, resulting in altered cell behavior, pathways, and molecular processes.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2021)
Article
Pathology
Li Wen, Jiye Gao, Leilei Huang, Dongmei Li, Guansheng Zhong
Summary: The study evaluated the clinical performance of NIPS for common trisomy and sex chromosome aneuploidy, showing high accuracy in detecting common trisomy and SCA. However, caution is needed in subsequent genetic counseling regarding the risk identified by Z-scores.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Obstetrics & Gynecology
Pe'er Dar, Bo Jacobsson, Cora MacPherson, Melissa Egbert, Fergal Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, Revital Faro, Rajeevi Madankumar, Lance Edwards, Sina Haeri, Robert Silver, Nidhi Vohra, Jon Hyett, Garfield Clunie, Zachary Demko, Kimberly Martin, Matthew Rabinowitz, Karen Flood, Ylva Carlsson, Georgios Doulaveris, Ciara Malone, Maria Hallingstrom, Susan Klugman, Rebecca Clifton, Charlly Kao, Hakon Hakonarson, Mary E. Norton
Summary: This study measured and compared the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy. The results showed that in women at a low risk for aneuploidy, cell-free DNA screening has high sensitivity and specificity. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Article
Endocrinology & Metabolism
Dylan C. Sarver, Cheng Xu, Leandro M. Velez, Susan Aja, Andrew E. Jaffe, Marcus M. Seldin, Roger H. Reeves, G. William Wong
Summary: In this study, a comprehensive and systematic analysis was conducted on the Ts65Dn trisomic mouse model to investigate the impact of gene dosage imbalance on whole-body metabolism. The results revealed altered metabolic parameters, including increased locomotor activity and energy expenditure, decreased fasting serum cholesterol levels, and mild glucose intolerance, in chow-fed Ts65Dn mice. When challenged with a high-fat diet, obese Ts65Dn mice showed dyslipidemia and impaired insulin sensitivity, as well as changes in mitochondrial activity and gene signatures related to fibrosis and inflammation in the liver and adipose tissue. Systems-level analysis identified conserved pathways and potential endocrine drivers contributing to dysregulated glucose and lipid metabolism.
MOLECULAR METABOLISM
(2023)