Article
Genetics & Heredity
Jonathan M. Chernus, Stephanie L. Sherman, Eleanor Feingold
Summary: Our study identified several genes with consistent patterns of association across groups and in certain subgroups, suggesting both generalized effects and specific effects in maternal nondisjunction of chromosome 21. While our results are epidemiological and cannot definitively prove mechanisms, the patterns we observed align with existing literature on associated genes.
PRENATAL DIAGNOSIS
(2021)
Article
Genetics & Heredity
Upamanyu Pal, Pinku Halder, Anirban Ray, Sumantra Sarkar, Supratim Dutta, Papiya Ghosh, Sujay Ghosh
Summary: In this study, variations in MCM9 were found to be associated with reduced recombination and nondisjunction of chromosome 21 during meiosis I in a maternal age-independent manner. These variants did not affect the position of chiasma formation. In Silico analyses suggested that some MCM9 variants may alter protein function due to amino acid substitution, as well as identified splice variants in MCM9. It is hypothesized that these polymorphisms predispose women to reduced recombination on chromosome 21 in oocytes at meiosis I, leading to the birth of a child with Down syndrome.
Article
Genetics & Heredity
Natalia V. Kovaleva
Summary: Nonhomologous meiotic co-orientation (NMC) was proposed to explain the interchromosomal effect (ICE) phenomenon, but subsequent studies did not support its meiotic nature. However, the NMC model still holds value in understanding the etiology of human aneuploidy. Analysis of data from 322 parental carriers of chromosomal abnormalities revealed unusual sex ratios in offspring, reflecting NMC between chromosomal abnormality and the X chromosome in spermatogenesis.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Nunzia Mollo, Miriam Aurilia, Roberta Scognamiglio, Lucrezia Zerillo, Rita Cicatiello, Ferdinando Bonfiglio, Pasqualina Pagano, Simona Paladino, Anna Conti, Lucio Nitsch, Antonella Izzo
Summary: Down syndrome is associated with upregulation of extracellular matrix (ECM) genes in the heart. The transcription factor RUNX1, located on chromosome 21, may potentially regulate the expression of these ECM genes. Silencing of RUNX1 in trisomic fetal fibroblasts reduces the expression of ECM genes and increases cell migration capacity.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Pinku Halder, Upamanyu Pal, Agnish Ganguly, Papiya Ghosh, Anirban Ray, Sumantra Sarkar, Sujay Ghosh
Summary: The aim of this study was to explore the association between maternal folate regulator gene polymorphisms and mutations and the incidence of chromosome 21 nondisjunction and Down syndrome births. The researchers tested the association between polymorphisms and mutations of DNMT3B and RFC1 genes and meiotic errors in the oocyte among 1215 Down syndrome child-bearing women and 900 controls. They found that a number of variants of DNMT3B and RFC1 exhibited an association with meiosis II nondisjunction independent of maternal age. The study also identified novel mutations and polymorphic variants unique to the Indian Bengali speaking cohort that increased the risk of meiosis II nondisjunction. In silico analyses predicted potential damages caused by these polymorphisms to the transcripts or proteins from the respective genes.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Genetics & Heredity
Francesca Antonaros, Rossella Zenatelli, Giulia Guerri, Matteo Bertelli, Chiara Locatelli, Beatrice Vione, Francesca Catapano, Alice Gori, Lorenza Vitale, Maria Chiara Pelleri, Giuseppe Ramacieri, Guido Cocchi, Pierluigi Strippoli, Maria Caracausi, Allison Piovesan
Summary: The study analyzed gene expression profiles of T21 and normal control blood cells, finding that the most over-expressed genes encode interferon-induced proteins and genes involved in mitochondrial translation and energy production were also altered.
Article
Genetics & Heredity
Jadranka Vranekovic, Ivana Babic Bozovic, Iva Bilic Cace, Bojana Brajenovic Milic
Summary: The study found a significant association between MTHFR gene polymorphisms and folate dietary intake with the stage of meiotic nondisjunction in mothers of children with maternally derived trisomy 21. Mothers with the CTAA, CTAC, and TTAA MTHFR genotype combinations had a 4.6-fold higher risk of MI nondisjunction of chromosome 21.
Article
Genetics & Heredity
Jakob Schuy, Jesper Eisfeldt, Maria Pettersson, Niloofar Shahrokhshahi, Mohsen Moslem, Daniel Nilsson, Niklas Dahl, Mansoureh Shahsavani, Anna Falk, Anna Lindstrand
Summary: Using induced pluripotent stem cells (iPSCs) from patients, researchers investigated the effects of partial monosomy on neural cells. RNA-Seq analysis revealed downregulation of multiple genes within the deleted region and global transcriptional dysregulation. A comparison with trisomy 21 cell lines showed opposite expression changes for genes on chromosome 21 and non-chromosome 21 genes.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, General & Internal
Carl P. Weiner, Mark L. Weiss, Helen Zhou, Argyro Syngelaki, Kypros H. Nicolaides, Yafeng Dong
Summary: The study suggests that maternal plasma RNA screening, tested by qRT-PCR and classified by machine learning, may accurately predict prenatal trisomy 21 (T21) at a lower cost than plasma DNA, providing potential for universal screening.
Article
Genetics & Heredity
Yasuhiro Kazuki, Feng J. Gao, Miho Yamakawa, Masumi Hirabayashi, Kanako Kazuki, Naoyo Kajitani, Sachiko Miyagawa-Tomita, Satoshi Abe, Makoto Sanbo, Hiromasa Hara, Hiroshi Kuniishi, Satoshi Ichisaka, Yoshio Hata, Moeka Koshima, Haruka Takayama, Shoko Takehara, Yuji Nakayama, Masaharu Hiratsuka, Yuichi Iida, Satoko Matsukura, Naohiro Noda, Yicong Li, Anna J. Moyer, Bei Cheng, Nandini Singh, Joan T. Richtsmeier, Mitsuo Oshimura, Roger H. Reeves
Summary: A transchromosomic rat model of Down syndrome (DS) was developed, showing DS-related characteristics such as learning and memory deficits, increased anxiety and hyperactivity, and reproducing well-characterized brain morphology, cerebellar size reduction, and anomalies in craniofacial morphology. This robust DS animal model can facilitate DS research and preclinical validation for drug development.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Cell Biology
Kourtney Sloan, Jared Thomas, Matthew Blackwell, Deanna Voisard, Eva Lana-Elola, Sheona Watson-Scales, Daniel L. Roper, Joseph M. Wallace, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Randall J. Roper
Summary: This study investigates the effects of triplicated genes on mouse skeletal phenotypes and finds that they can both improve and worsen bone deficits.
DISEASE MODELS & MECHANISMS
(2023)
Article
Medicine, General & Internal
Melissa J. Alldred, Sang Han Lee, Stephen D. Ginsberg
Summary: Down syndrome is a genetic disorder caused by the triplication of chromosome 21, leading to neurological and physiological pathologies which worsen with age. Maternal choline supplementation may attenuate cognitive decline in DS and AD mouse models. The dysregulation of adiponectin (APN) in the brain could be an early marker of cognitive decline and neurodegeneration, suggesting its potential as a biomarker for AD pathology.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Anna J. Moyer, Fabian-Xose Fernandez, Yicong Li, Donna K. Klinedinst, Liliana D. Florea, Yasuhiro Kazuki, Mitsuo Oshimura, Roger H. Reeves
Summary: Trisomy 21 and mutations in the Sonic hedgehog (SHH) signaling pathway lead to similar phenotypes, including cerebellar hypoplasia, craniofacial abnormalities, congenital heart defects, and Hirschsprung disease. Overexpression of human chromosome 21 genes disrupts normal SHH signaling during development and affects the phenotypes. By overexpressing 163 chromosome 21 genes in SHH-responsive mouse cell lines and analyzing cerebellar samples from Down syndrome mouse models, this study identified genes that upregulate or inhibit SHH signaling. The findings prioritize dosage-sensitive chromosome 21 genes for further studies and suggest potential therapeutic targets to ameliorate Down syndrome phenotypes.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Andrei Semikhodskii, Tatiana Makarova, Daria Sutyagina
Summary: Uniparental disomy (UPD) is a rare chromosomal condition that can lead to genetic inconsistencies in parentage DNA testing. We present a case of trio paternity test where multiple inconsistent markers were found on chromosome 21, indicating maternal heterodisomy. This case highlights the importance of considering UPD as a potential cause of genetic inconsistencies, especially when markers are located on the same chromosome.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Obstetrics & Gynecology
Chih-Ping Chen, Te-Yao Hsu, Schu-Rern Chern, Peih-Shan Wu, Shin -Wen Chen, Liang-Kai Wang, Fang-Tzu Wu, Yen -Ting Pan, Yun-Yi Chen, Wayseen Wang
Summary: We present a case of mosaic trisomy 21 in amniocentesis in a twin pregnancy that resulted in a favorable fetal outcome. The maternal uniparental disomy (UPD) 21 and postnatal decrease of the trisomy 21 cell line were also observed. This case highlights the transient and benign nature of mosaic trisomy 21 and emphasizes the importance of considering UPD 21.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2023)