scholarly journals Molecular and Comparative Genetics of Mental Retardation

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 835-881 ◽  
Author(s):  
Jennifer K Inlow ◽  
Linda L Restifo
Keyword(s):  
Mental Retardation ◽  
Homo Sapiens ◽  
System Development ◽  
Laboratory Data ◽  
Fruit Fly ◽  
Mendelian Inheritance ◽  
Nervous System Development ◽  
Skewed Distribution ◽  
Therapeutic Drug ◽  
Cellular Mechanisms

Abstract Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the ∼700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR.

scholarly journals Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1453
Author(s):  
Joaquín Martí-Clúa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Current Data ◽  
Cellular Mechanisms ◽  
Dividing Cells ◽  
The Central Nervous System ◽  
Repeated Doses ◽  
Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

scholarly journals The Nematode Caenorhabditis elegans A Model Animal “Made for Microscopy”

2004 ◽  
Vol 12 (2) ◽  
pp. 8-13
Author(s):  
David H. Hall
Keyword(s):  
Caenorhabditis Elegans ◽  
System Development ◽  
Scientific Discovery ◽  
Medical Science ◽  
Model Organism ◽  
Small Animal ◽  
Single Species ◽  
Fruit Fly ◽  
Nervous System Development ◽  
Model Animal

The small unassuming nematode, Caenorhabditis elegans is only one millimeter long and lives in the soil munching on bacteria. While many nematode (roundworm) species are parasites with medical or agricultural importance, C. elegans seems to harm no one. Yet, this animal has attained a status in medical science that compares to more complex organisms such as the mouse or fruit fly in its utility for scientific discovery. It has been the subject of thousands of studies dealing with topics as diverse as nutrition, aging, and nervous system development. About 5000 scientists are now pursuing this single species in hundreds of laboratories worldwide. In 2002, the Nobel Prize in Medicine was awarded to three of the pioneers in establishing C. elegans as a “model organism“: Sydney Brenner, John Sulston, and H. Robert Horvitz. Why study worms?Sydney Brenner first turned his attention to C. elegans in the 1960's. Working at the Medical Research Council in England, he was looking for a small animal with inexpensive tastes that could be easily cultured in the laboratory.

31 Gametic Incompatibility: Improving the Success of Mate Allocation in Dairy Cattle

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 16-17
Author(s):  
Audrey A A Martin ◽  
Samir Id-Lahoucine ◽  
Dan Tulpan ◽  
Stephen J Leblanc ◽  
Angela Cánovas ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
System Development ◽  
Enrichment Analysis ◽  
Mendelian Inheritance ◽  
Nervous System Development ◽  
Transmission Ratio Distortion ◽  
Reproductive Capacity ◽  
Pathway Enrichment Analysis ◽  
Inbreeding Coefficients ◽  
Offspring Genotype

Abstract In the dairy industry, mate allocation is mainly based on the parents’ breeding values and inbreeding coefficients aiming to achieve the producer’s breeding goal. With artificial insemination, the portfolio of sires to choose from is large and the quality of the semen doses is standardized. However, not all sire-dam matings are equally likely to produce a successful pregnancy. Among other reproduction issues, the success of a mating could vary due to the incompatibility of gametes coming from the sire and the dam and could influence the fertilization’s success, additionally to the reproductive capacity of the parents. Considering the gametic incompatibility of the potential parents could be a novel option to improve mating plans. Under the hypothesis that gametic incompatibility has a significant effect on reproduction and reduces the odds of fertilization and pregnancy, this study aimed to determine the genetic background of gametic incompatibility. Transmission ratio distortion (TRD), which detects deviations from Mendelian inheritance expectations, is commonly used to identify deleterious mutations. We adapted the TRD model by including an interaction effect between the gametes leading to the offspring genotype to detect regions with TRD effects and gametic incompatibility. Our dataset contained 436,651 genotyped (50K SNP) Canadian Holstein cattle from 283,817 parents-offspring trios. A total of 482 regions with TRD containing 671 positional genes were found. The functional analysis detected biological pathways associated with uterus development, embryonic skeletal system development, and nervous system development. Additionally, gene ontology terms from the topology-based pathway enrichment analysis were mostly related to the steroid hormones signalling pathway. Although difficult, genes specific to gametic incompatibility could be differentiated from genes underlying other reproduction processes by refining the genetic regions with TRD. With further investigation, we will provide new information to improve mate allocation for the dairy cattle industry.

No pun intended: future directions in invertebrate glial cell migration studies

2007 ◽  
Vol 3 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Patrick Cafferty ◽  
Vanessa J. Auld
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Glial Cell ◽  
Glial Cells ◽  
Molecular Mechanisms ◽  
System Development ◽  
Fruit Fly ◽  
Nervous System Development ◽  
Wide Range ◽  
And Function

AbstractGlial cells play a wide range of essential roles in both nervous system development and function and has been reviewed recently (Parker and Auld, 2006). Glia provide an insulating sheath, either form or direct the formation of the blood–brain barrier, contribute to ion and metabolite homeostasis and provide guidance cues. Glial function often depends on the ability of glial cells to migrate toward specific locations during nervous system development. Work in nervous system development in insects, in particular in the fruit fly Drosophila melanogaster and the tobacco hornworm Manduca sexta, has provided significant insight into the roles of glia, although the molecular mechanisms underlying glial cell migration are being determined only now. Indeed, many of the processes and mechanisms discovered in these simpler systems have direct parallels in the development of vertebrate nervous systems. In this review, we first examine the developmental contexts in which invertebrate glial cell migration has been observed, we next discuss the characterized molecules required for proper glial cell migration, and we finally discuss future goals to be addressed in the study of glial cell development.

scholarly journals PGAP3 Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1782
Author(s):  
Sahar I. Da’as ◽  
Waleed Aamer ◽  
Waseem Hasan ◽  
Aljazi Al-Maraghi ◽  
Alya Al-Kurbi ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Early Development ◽  
Motor Neurons ◽  
System Development ◽  
Tube Formation ◽  
Nervous System Development ◽  
Global Developmental Delay ◽  
Recessive Mutations ◽  
Fetal Movements ◽  
Neuromuscular Responses

Recessive mutations in Post-GPI attachment to proteins 3 (PGAP3) cause the rare neurological disorder hyperphosphatasia with mental retardation syndrome 4 type (HPMRS4). Here, we report a novel homozygous nonsense mutation in PGAP3 (c.265C>T-p.Gln89*), in a 3-year-old boy with unique novel clinical features. These include decreased intrauterine fetal movements, dysgenesis of the corpus callosum, olfactory bulb agenesis, dysmorphic features, cleft palate, left ear constriction, global developmental delay, and hypotonia. The zebrafish functional modeling of PGAP3 loss resulted in HPMRS4-like features, including structural brain abnormalities, dysmorphic cranial and facial features, hypotonia, and seizure-like behavior. Remarkably, morphants displayed defective neural tube formation during the early stages of nervous system development, affecting brain morphogenesis. The significant aberrant midbrain and hindbrain formation demonstrated by separation of the left and right tectal ventricles, defects in the cerebellar corpus, and caudal hindbrain formation disrupted oligodendrocytes expression leading to shorter motor neurons axons. Assessment of zebrafish neuromuscular responses revealed epileptic-like movements at early development, followed by seizure-like behavior, loss of touch response, and hypotonia, mimicking the clinical phenotype human patients. Altogether, we report a novel pathogenic PGAP3 variant associated with unique phenotypic hallmarks, which may be related to the gene’s novel role in brain morphogenesis and neuronal wiring.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li
Keyword(s):  
Brain Damage ◽  
Intracellular Signaling ◽  
System Development ◽  
Intrauterine Infection ◽  
Artery Occlusion ◽  
Nervous System Development ◽  
Human Infants ◽  
Hypoxic Ischemia ◽  
Show Evidence ◽  
The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

Antenatal Glucocorticoids Supplementation and Central Nervous System Development

2013 ◽  
Vol 14 (2) ◽  
pp. 160-166
Author(s):  
Diego Gazzolo ◽  
Laura D. Serpero ◽  
Alessandro Frigiola ◽  
Raul Abella ◽  
Alessandro Giamberti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Central Nervous System Development

Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review

2020 ◽  
Vol 20 (17) ◽  
pp. 1781-1790
Author(s):  
Noor Anisah Abu Yazit ◽  
Norsham Juliana ◽  
Srijit Das ◽  
Nur Islami Mohd Fahmi Teng ◽  
Nadia Mohd Fahmy ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Chromosomal Abnormalities ◽  
Current Knowledge ◽  
System Development ◽  
Genetic Disorder ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Importance ◽  
Nervous System Development ◽  
Micro Rna ◽  
A Genome

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.

Sign in / Sign up

Export Citation Format

Share Document