The origin of the extra chromosome 21 in Down syndrome

1978 ◽  
Vol 20 (1-6) ◽  
pp. 194-203 ◽  
Author(s):  
A. Hansson ◽  
M. Mikkelsen
Keyword(s):  
Down Syndrome ◽  
Extra Chromosome ◽  
Chromosome 21

Ts65Dn, a Mouse Model of Down Syndrome, Exhibits Increased GABAB-Induced Potassium Current

2007 ◽  
Vol 97 (1) ◽  
pp. 892-900 ◽  
Author(s):  
Tyler K. Best ◽  
Richard J. Siarey ◽  
Zygmunt Galdzicki
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Extra Chromosome ◽  
Functional Expression ◽  
Chromosome 21 ◽  
Fluctuation Analysis ◽  
Response Curves ◽  
Girk Channel

Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase (∼2-fold) in GABAB-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABAB receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

scholarly journals Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors -A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Pilar Osuna-Marco ◽  
Mónica López-Barahona ◽  
Blanca López-Ibor ◽  
Águeda Mercedes Tejera
Keyword(s):  
Down Syndrome ◽  
Solid Tumors ◽  
Tumor Suppressor Genes ◽  
Wilms Tumor ◽  
Extra Chromosome ◽  
Germ Cell Tumors ◽  
Chromosome 21 ◽  
Testicular Tumors ◽  
Unique Pattern ◽  
Increased Risk

People with Down syndrome have unique characteristics as a result of the presence of an extra chromosome 21. Regarding cancer, they present a unique pattern of tumors, which has not been fully explained to date. Globally, people with Down syndrome have a similar lifetime risk of developing cancer compared to the general population. However, they have a very increased risk of developing certain tumors (e.g., acute leukemia, germ cell tumors, testicular tumors and retinoblastoma) and, on the contrary, there are some other tumors which appear only exceptionally in this syndrome (e.g., breast cancer, prostate cancer, medulloblastoma, neuroblastoma and Wilms tumor). Various hypotheses have been developed to explain this situation. The genetic imbalance secondary to the presence of an extra chromosome 21 has molecular consequences at several levels, not only in chromosome 21 but also throughout the genome. In this review, we discuss the different proposed mechanisms that protect individuals with trisomy 21 from developing solid tumors: genetic dosage effect, tumor suppressor genes overexpression, disturbed metabolism, impaired neurogenesis and angiogenesis, increased apoptosis, immune system dysregulation, epigenetic aberrations and the effect of different microRNAs, among others. More research into the molecular pathways involved in this unique pattern of malignancies is still needed.

scholarly journals Gambaran Erupsi Gigi Permanen pada Anak Sindrom Down Usia 10-16 Tahun di Sekolah Luar Biasa Kabupaten Jember

2018 ◽  
Vol 8 (1) ◽  
pp. 8
Author(s):  
Loly Anastasya Sinaga ◽  
Dwi Kartika Apriyono ◽  
Masniari Novita
Keyword(s):  
Down Syndrome ◽  
Special Needs ◽  
Physical Characteristic ◽  
Trisomy 21 ◽  
Genetic Disorder ◽  
Extra Chromosome ◽  
Descriptive Study ◽  
Chromosome 21 ◽  
Permanent Teeth ◽  
Intellectual Abilities

Background: Down Syndrome is a genetic disorder that occurs because of chromosome 21 has three chromosome (trisomy 21). The extra chromosome changes the genetic balance, physical characteristic, intellectual abilities, and physiological body function. Tooth eruption in Down Syndrome children typically delayed in both the timing and sequence of eruption up to two or three years. Objective: To observe the permanent teeth eruption in Down syndrome children at age 10-16 years old, boys and girls in Special Needs School in Jember. Materials and Methods: This research was a descriptive study with 7 subjects. Each subject was examined then calculated teeth that had emerged or functionally eruption with articualting paper. Result and Conclusion:  Both permanent teeth that is still partially erupted tooth (emerged/ EM) and had erupted perfectly (functionally eruption/ FE) delayed in eruption in Down Syndrome boys and girls at age 10-16 years old.

Imbalances of Chromosome 21 in MDS/AML Include Cryptic Deletions but NOT RUNX1 Amplifications.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2561-2561
Author(s):  
Katya Gancheva ◽  
Diana Brazma ◽  
Nahid Zarein ◽  
Julie Howard-Reeves ◽  
Phaidra Partheniou ◽  
...  
Keyword(s):  
Down Syndrome ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Extra Chromosome ◽  
Chromosome 21 ◽  
Oligonucleotide Array ◽  
Fish Analysis ◽  
Extra Copy ◽  
Commercial Fish

Abstract Abstract 2561 We present the results of a study demonstrating that the genome profile of RUNX1 in MDS/AML is characterised by hitherto unreported partial deletions and absence of amplifications. This is in stark contrast to reports of chromosome 21 amplifications in ALL. We speculate that the absence of RUNX1 deletions results from them being well below a size detectable by commercial FISH probes. Extra chromosome 21 is the second most common acquired trisomy after (+) 8 in adult myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). It is rarely observed as sole abnormality but seen as part of complex karyotype in some 3–7% of the AML (Atlas of Genetics and Cytogenetics in Oncology and Haematology, http://atlasgeneticsoncology.org). Although the gene(s) in trisomy 21 associated with leukemia are unknown, the 21q22 region appears to be critical since it houses the RUNX1 gene. Multiple amplified copies of the RUNX1 carried by marker chromosomes, such as iAML21, are described in both acute lymphoblastic leukemia (ALL) and AML. A common 5.1 Mb amplification containing the RUNX1, miR-802 and genes mapping to the Down syndrome critical region identified in 91 children with iAML21, was shown to be the likely initiating event in this rare form of childhood B-cell ALL (Rand et al., Blood, 2011). In contrast, recent studies of AML in a Down syndrome and a constitutionally normal individual showed lack of RUNX1, ETS2 and ERG involvement (Canzonetta et al., BJH, 2012). Here we present 16 MDS/AML cases with imbalances of chromosome 21 identified by genomic array screening from a cohort of 83 cases. Whole genome screening (aCGH) was performed on presentation samples of MDS /AML and de novo AML cases using an oligonucleotide array platform (Agilent) at 60K, 244K, 400K and 1M density. G banding and FISH analysis were also successfully performed. Gain of an extra copy (trisomy) of chromosome 21 (+21) was found in 9 patients, all but one with complex karyotypes. In 2 AMLs high level amplifications were detected at 21q22, which involved the ETS2 and ERG but not the RUNX1 sequences. While several commercially available RUNX1 FISH probes showed gene multiple signals, custom FISH probes covering the relevant regions confirmed that the amplifications excluded the RUNX1 but affected both EST2 and ERG thus rendering the commercial probes unfit to assess CNA in this genome area. In another two cases with trisomy 12, cryptic loss of 43Kb and 98Kb resp. within the RUNX1 sequences was detected and confirmed by FISH. Furthermore, similar deletions within the 21q22.12 were also found in another 7 cases all of which had diploid set of chromosome 21 but had multiple changes at G banding level and high TGA score. These RUNX1 deletions were variable in size, ranging from 98Kb to 2.7Mb. Although our observations excluded clinical correlations it is note worthy that most of the patients with RUNX1 loss have not achieved complete cytogenetic remission. These findings suggest role for the RUNX1 loss as indicator of progressive disease and provide a novel insight into pathogenesis of MDS/AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of the head circumference measurement between Down syndrome and normal children

2012 ◽  
Vol 24 (2) ◽  
Author(s):  
Nur Hanis Adibah Yahya ◽  
Ratna Indriyanti ◽  
Rudy Hartanto
Keyword(s):  
Down Syndrome ◽  
Head Circumference ◽  
Extra Chromosome ◽  
Mean Value ◽  
Chromosome 21 ◽  
Normal Children ◽  
Cross Sectional ◽  
Children With Down Syndrome ◽  
Value Of Children ◽  
And Gender

Introduction: Growth and development assessment in children is measured by the head circumference measurement or as known as occipital-frontal circumference. In cases of genetic abnormalities such as Down syndrome which is caused by extra chromosome 21, give distinct features in the craniofacial profile, hence the author finds it is useful to observe the changes in their growth, mainly the head circumference. The purpose of this research is to analized comparison between head circumference measurement in children with Down syndrome in Sekolah Luar Biasa-C and normal children, Methods: Type of this research is analytical with surveying technique, using cross sectional studies on 20 children with Down syndrome and 160 normal children 6 to 13 years old. The sample subject. Based on anthropometry landmark on point Glabella to Opisthocranion, measurement is taken using a non-stretchable, flexible measuring tape. Result: There are significant differences between the head circumference of children in both group according to age and gender; except age 6 male, with the mean value of children with Down syndrome compare to normal circumference measurement were smaller 3 to 5 cm behind the normal children in this research. Conclusion: The head circumference of the children with Down syndrome over all from age 6 to 13 years old were smaller than the regular children in same age and same gender.

No Evidence for Genomic Imprinting in Liver-Born Down Syndrome Patients

1996 ◽  
Vol 45 (1-2) ◽  
pp. 265-271 ◽  
Author(s):  
C. Stoll ◽  
Y. Alembik ◽  
B. Dott ◽  
J. Feingold
Keyword(s):  
Down Syndrome ◽  
Genomic Imprinting ◽  
Extra Chromosome ◽  
Chromosome 21 ◽  
Parental Origin ◽  
Maternal Origin ◽  
Paternal Origin ◽  
Cytogenetic Analyses ◽  
Down Syndrome Phenotype

AbstractDespite numerous studies, the clinical heterogeneity of Down syndrome has no explanation. We have attempted to investigate the role of genomic imprinting in the phenotype of liveborn Down syndrome patients. Hundred fifty eight patients were investigated for parental origin of the extra chromosome 21 with standard cytogenetic analyses and with DNA plymorphic markers. The extra chromosome 21 was of paternal origin in 8 cases and of maternal origin in 150 cases.The phenotype of Down svndrome patients in whom the nondisjunction was of maternal origin, was not different from the phenotype of Down syndrome patients in whom the nondisjunction was of paternal origin.We conclude that imprinting may probably not play a role in the heterogeneity of Down syndrome phenotype.

scholarly journals Parental age and the origin of extra chromosome 21 in Down syndrome

2001 ◽  
Vol 46 (6) ◽  
pp. 347-350 ◽  
Author(s):  
A. Jyothy ◽  
K. S. D. Kumar ◽  
G.N. Mallikarjuna Rao ◽  
V. Babu Rao ◽  
B. Uma Devi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Extra Chromosome ◽  
Chromosome 21 ◽  
Parental Age
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