scholarly journals Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of down syndrome-related phenotypes

2021 ◽  
Author(s):  
Eva Lana-Elola ◽  
Heather Cater ◽  
Sheona Watson-Scales ◽  
Simon Greenaway ◽  
Jennifer Müller-Winkler ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Cognitive Deficits ◽  
Trisomy 21 ◽  
Heart Defects ◽  
Chromosome 21 ◽  
Phenotypic Analysis ◽  
Extra Copy ◽  
Human Chromosome 21 ◽  
Complex Phenotypes ◽  
Physiological Systems

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish if this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder.

scholarly journals Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down Syndrome-related phenotypes

2021 ◽  
Author(s):  
Eva Lana-Elola ◽  
Heather Cater ◽  
Sheona Watson-Scales ◽  
Simon Greenaway ◽  
Jennifer Müller-Winkler ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Bone Density ◽  
Cognitive Deficits ◽  
Trisomy 21 ◽  
Heart Defects ◽  
Chromosome 21 ◽  
Phenotypic Analysis ◽  
Extra Copy ◽  
Human Chromosome 21 ◽  
Complex Phenotypes

AbstractDown syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, causative genes remain mostly unknown. Animal models enable identification of these genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. Here, we comprehensively phenotype Dp1Tyb mice and find wide-ranging DS-like phenotypes including aberrant megakaryopoiesis, reduced bone density, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for studies of many complex DS phenotypes.

scholarly journals Consequences of aneuploidy in human fibroblasts with trisomy 21

2020 ◽  
Author(s):  
Sunyoung Hwang ◽  
Paola Cavaliere ◽  
Rui Li ◽  
Lihua Julie Zhu ◽  
Noah Dephoure ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Human Fibroblasts ◽  
Fold Increase ◽  
Trisomy 13 ◽  
Chromosome 21 ◽  
Phenotypic Analysis ◽  
Extra Copy ◽  
Protein Levels ◽  
Post Transcriptional Regulation

AbstractAn extra copy of chromosome 21 causes Down syndrome, the most common genetic disease in humans. The mechanisms by which the aneuploid status of the cell, independent of the identity of the triplicated genes, contributes to the pathologies associated with this syndrome are not well defined. To characterize aneuploidy driven phenotypes in trisomy 21 cells, we performed global transcriptome, proteome, and phenotypic analysis of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes. On average, mRNA and protein levels show a 1.5 fold increase in all trisomies with a subset of proteins enriched for subunits of macromolecular complexes showing signs of post-transcriptional regulation. Furthermore, we show several aneuploidy-associated phenotypes are present in trisomy 21 cells, including lower viability and an increased dependency on the serine-driven lipid biosynthesis pathway to proliferate. Our studies present a novel paradigm to study how aneuploidy contributes to Down syndrome.

scholarly journals Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR‐DSCR) on human chromosome 21

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Maria Chiara Pelleri ◽  
Elena Cicchini ◽  
Michael B. Petersen ◽  
Lisbeth Tranebjærg ◽  
Teresa Mattina ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Human Chromosome ◽  
Critical Region ◽  
Trisomy 21 ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Human Chromosome 21

scholarly journals Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

2019 ◽  
Author(s):  
Pishan Chang ◽  
Daniel Bush ◽  
Stephanie Schorge ◽  
Mark Good ◽  
Tara Canonica ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Models ◽  
Cognitive Deficits ◽  
Memory Task ◽  
Chromosome 21 ◽  
Neural Dynamics ◽  
Human Chromosome 21 ◽  
Chromosomal Disorder ◽  
Reduced Frequency ◽  
High Gamma

SummaryAltered neural dynamics in medial prefrontal cortex (mPFC) and hippocampus may contribute to cognitive impairments in the complex chromosomal disorder, Down Syndrome (DS). Here, we demonstrate non-overlapping behavioural differences associated with distinct abnormalities in hippocampal and mPFC electrophysiology during a canonical spatial memory task in three partially trisomic mouse models of DS (Dp1Tyb, Dp10Yey, Dp17Yey) that together cover all regions of homology with human chromosome 21 (Hsa21). Dp1Tyb mice showed slower decision-making (unrelated to the gene dose of DYRK1A, which has been implicated in DS cognitive dysfunction) and altered theta dynamics (reduced frequency, increased hippocampal-mPFC coherence, increased modulation of hippocampal high gamma); Dp10Yey mice showed impaired alternation performance and reduced theta modulation of hippocampal low gamma; while Dp17Yey mice were no different from wildtype mice. These results link specific hippocampal and mPFC circuit dysfunctions to cognitive deficits in DS models and, importantly, map them to discrete regions of Hsa21.

Down Syndrome

2017 ◽  
Author(s):  
George T Capone
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Developmental Delays ◽  
Gene Dosage ◽  
Adult Life ◽  
Chromosome 21 ◽  
Extra Copy ◽  
Anatomical Features ◽  
Primary Mechanism ◽  
Dosage Imbalance

People with Down syndrome (trisomy 21) are distinguished by having an extra copy of chromosome 21. Chromosome 21 contains an estimated 562 genes, including 161 known to code for functional proteins, and at least 396 considered novel. Gene dosage imbalance is the primary mechanism, which results in the molecular, cellular, histological, and anatomical features characteristic of the condition. Throughout brain development, major neurobiological events go awry, resulting in a differently organized brain and characteristic developmental delays noted during infancy and the preschool years. The consequences of gene dosage imbalance continue to have repercussions on neurobiological function throughout childhood and adult life.

scholarly journals Congenital Chylothorax in Newborn with Trisomy 21

2021 ◽  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Rare Complication ◽  
Extra Chromosome ◽  
Chromosome 21 ◽  
Abnormal Development ◽  
Chromosomal Anomalies ◽  
Extra Copy ◽  
Genetic Abnormalities ◽  
Congenital Chylothorax

Dawn syndrome Trisomy 21 means there’s an extra copy of chromosome 21 in every cell. This is the most common form of Down syndrome, there is three types of Down syndrome. Trisomy 21 which there is an extra copy of chromosome 21 in every cell. Mosaicism occurs when a child is born with an extra chromosome in some but not all of their cells. Translocation in this type of Down syndrome, children have only an extra part of chromosome 21. There are 46 total chromosomes. However, one of them has an extra piece of chromosome 21 attached. Down syndrome is associated with a lots of complication like congenital heart disease. Vision. Hearing behavior and mental problem. Our case is Down syndrome with congenital chylothorax which is rare complication. Neonatal chylothorax results from the accumulation of chyle in the pleural space and may be either congenital or an acquired condition. Congenital chylothorax is most likely due to abnormal development or obstruction of the lymphatic system. It is often associated with hydrops fetalis. It can be idiopathic or may be associated with various chromosomal anomalies including Trisomy 21, Turner syndrome, Noonan syndrome, and other genetic abnormalities [1]. Treatment of chylothorax is multidisplenery need insertion of chest tube to decrease respiratory distress, diet management and pediatric surgery.

Molecular Cytogenetic Classification of Down Syndrome and Screening of Somatic Aneuploidy in Mothers

2021 ◽  
pp. 1-9
Author(s):  
Sushil Kumar Jaiswal ◽  
Ashok Kumar ◽  
Amit Kumar Rai
Keyword(s):  
Down Syndrome ◽  
Peripheral Blood ◽  
Trisomy 21 ◽  
Health Management ◽  
Chromosome 21 ◽  
Robertsonian Translocations ◽  
Significant Difference ◽  
And Control

Down Syndrome (DS) caused by trisomy 21 results in various congenital and developmental complications in children. It is crucial to cytogenetically diagnose the DS cases early for their proper health management and to reduce the risk of further DS childbirths in mothers. In this study, we performed a cytogenetic analysis of 436 suspected DS cases using karyotyping and fluorescent in situ hybridization. We detected free trisomies (95.3%), robertsonian translocations (2.4%), isochromosomes (0.6%), and mosaics (1.2%). We observed a slightly higher incidence of DS childbirth in younger mothers compared to mothers with advanced age. We compared the somatic aneuploidy in peripheral blood of mothers having DS children (MDS) and control mothers (CM) to identify biomarkers for predicting the risk for DS childbirths. No significant difference was observed. After induced demethylation in peripheral blood cells, we did not observe a significant difference in the frequency of aneuploidy between MDS and CM. In conclusion, free trisomy 21 is the most common type of chromosomal abnormality in DS. A small number of DS cases have translocations and mosaicism of chromosome 21. Additionally, somatic aneuploidy in the peripheral blood from the mother is not an effective marker to predict DS childbirths.

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