All Creatures Great and Small: New Approaches for Understanding Down Syndrome Genetics.
Ontology highlight
ABSTRACT:
SUBMITTER: Moyer AJ
PROVIDER: S-EPMC8208824 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Gilles de la Tourette syndrome (TS) is a common, childhood-onset psychiatric disorder characterized by persistent motor and vocal tics. It is a heterogeneous disorder in which the phenotypic expression may be affected by environmental factors, such as immune responses. Furthermore, several studies have shown that genetic factors play a vital role in the etiology of TS, as well as its comorbidity with other disorders, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder. TS has a complex inheritance pattern and, according to various genetic studies, several genes and loci have been correlated with TS. Genome-wide linkage studies have identified Slit and Trk-like 1 (SLITRK1) and histidine decarboxylase (HDC) genes, and candidate gene association studies have extensively investigated the dopamine and serotonin system genes, but there have been no consistent results. Moreover, genome-wide association studies have implicated several genetic loci; however, larger study cohorts are needed to confirm this. Copy number variations, which are polymorphisms in the number of gene copies due to chromosomal deletions or duplications, are considered another significant source of mutations in TS. In the last decade, whole genome/exome sequencing has identified several novel genetic mutations in patients with TS. In conclusion, more studies are needed to reveal the exact mechanisms of underlying TS, which may help to provide more information on the prognosis and therapeutic plans for TS.
| S-EPMC9250083 | biostudies-literature
Project description:In juvenile idiopathic arthritis (JIA), there are now more than 25 regions represented by single nucleotide polymorphisms that show strong genetic associations. The causal variants and corresponding functions have not yet been defined for the majority of these regions. Here, we review current JIA association findings and the recent progress in the annotation of noncoding portion of the human genome as well as the new technologies necessary to apply this knowledge to JIA association findings.An international collaboration was able to amass sufficient numbers of JIA and control samples to identify significantly robust genetic associations for JIA. The Encyclopedia of DNA Elements project and the National Institutes of Health (NIH) Roadmap Epigenetics Program have now annotated more than 80% of the noncoding genome, important in understanding the impact of risk loci, the majority of which fall outside of protein coding regions. Recent technological advances in high throughput sequencing, chromatin structure determination, transcription factor and enhancer binding site mapping and genome editing will likely provide a basis for understanding JIA genetic risk.Understanding the role of genetic variation in the cause of JIA will provide insight for disease mechanism and may explain disease heterogeneity between JIA subtypes and between autoimmune diseases in general.
| S-EPMC4445412 | biostudies-literature
Project description:Background: Down syndrome (DS) is associated with poor language skills that seem disproportionate to general nonverbal ability, but the nature and causes of this deficit are unclear. We assessed how individuals with DS understand complex linguistic constructions, and considered how cognitive ability and memory and impact the ability of those with DS to process these sentence types. Methods: There were three groups participating in the study: children with DS (n = 33) and two control groups composed of children with cognitive impairment of unknown aetiology (CI) (n = 32) and children with typical development (n = 33). The three groups did not differ on raw scores on a test of non-verbal cognitive ability. Using a newly devised animation task, we examined how well individuals with DS (n = 33) could understand relative clauses, complement clauses and adverbial clauses compared to children with CI and typically developing controls. Participants also completed the Test for the Reception of Grammar-2, three measures of memory (forward and backward digit recall, visuo-spatial memory) and a hearing screen. Results: Results indicated that (1) with the exception of intransitive subject relative clauses, children with DS performed at floor on all other complex sentences, (2) they performed at a significantly lower level than both control groups, and (3) DS status accounted for a significant proportion of the variance over and above memory skills. Conclusions: Our findings suggest that children with DS have a disproportionate difficulty understanding complex sentences compared to two control groups matched on mental age. Furthermore, their understanding of syntax is not completely explained by poor cognitive or memory skills, rather it appears to be a specific deficit that may distinguish children with DS from other neurodevelopmental disorders.
| S-EPMC6259485 | biostudies-literature
Project description:We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment was reviewed by genetics experts, validated by student interviews, and taken by >600 students at three institutions. Normalized learning gains on the GCA were positively correlated with averaged exam scores, suggesting that the GCA measures understanding of topics relevant to instructors. Statistical analysis of our results shows that differences in the item difficulty and item discrimination index values between different questions on pre- and posttests can be used to distinguish between concepts that are well or poorly learned during a course.
| S-EPMC2592048 | biostudies-literature
Project description:Microtubule associated serine/threonine kinase (MASTL) is an important Ser/Thr kinase belonging to the family of AGC kinases. It is the human orthologue of Greatwall kinase (Gwl) that plays a significant role in mitotic progression and cell cycle regulation. Upregulation of MASTL in various cancers and its association with poor patient survival establishes it as an important drug target in cancer therapy. Nevertheless, the target remains unexplored with the paucity of studies focused on identification of inhibitors against MASTL, which emphasizes the relevance of our present study. We explored various drug databases and performed virtual screening of compounds from both natural and synthetic sources. A list of promising compounds displaying high binding characteristics towards MASTL protein is reported. Among the natural compounds, we found a 6-hydroxynaphthalene derivative ZINC85597499 to display best binding energy value of -9.32?kcal/mol. While among synthetic compounds, a thieno-pyrimidinone based tricyclic derivative ZINC53845290 compound exhibited best binding affinity of value -7.85?kcal/mol. MASTL interactions with these two compounds were further explored using molecular dynamics simulations. Altogether, this study identifies potential inhibitors of human Gwl kinase from both natural and synthetic origin and calls for studying these compounds as potential drugs for cancer therapy.
| S-EPMC5861128 | biostudies-literature
Project description:Peri-implant bone loss leading to dental implant failure does not develop in the same way across subjects who apparently present the same condition-specifically, in the case of Down syndrome patients with the same genetic disorder-given that they do not necessarily develop immune-inflammatory disorders to the same extent. METHODS:This retrospective case-control study was aimed at identifying the possible genes involved in implant failure in Down syndrome patients by matching the periodontal disease variable by means of a retrospective case-control study. This process involved using the functional analysis of gene expression software Transcriptome Analysis Console (TAC, Affymetrix, Thermo Fisher Scientific, Waltham, MA, USA) and a search for the possible candidate genes involved. Focus was placed on the 92 genes related to the inflammation identified from the TaqMan™ Array Plate Human Inflammation Kit (Thermo Fisher Scientific, Waltham, MA, USA). RESULTS:Six genes showed statistically significant results (p < 0.05) in our comparison. Three of them-PLCG2 (p = 0.0333), ALOX5 (p = 0.03) and LTAH4 (p = 0.0081)-were overexpressed in the implant reject group, and the following three were down-regulated: VCAM1 (p = 0.0182), PLA2G2A (p = 0.0034) and PLA2G10 (p = 0.047). CONCLUSION:Statistically significant differences exist in the gene expression involved in osteoclastogenesis, inflammatory response and host defensive response.
| S-EPMC7464703 | biostudies-literature
Project description:Understanding phenotypes and their genetic determinants for metabolic syndrome (MetS) has been quite challenging. With the advent of systems genomic approaches, there is a need to decipher methods for identification and evaluating the functional role of phenotypic traits associated with complex diseases, such as MetS. The monogenic syndromes of lipodystrophy are well understood, but the molecular pathophysiology of insulin resistance (IR) underpinning the obesity, diabetes mellitus, and dyslipidemia is not well deciphered. In this commentary, we argue the role of pathophysiology of MetS, and its effects into possible understanding of genetic determinants associated with lipodystrophy-mediated diabetes mellitus.
| S-EPMC6163883 | biostudies-literature
Project description:Down syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability (ID). Although ID can be mild, the average intelligence quotient is in the range of 40-50. All individuals with DS will also develop the neuropathology of Alzheimer's disease (AD) by the age of 30-40 years, and approximately half will display an AD-like dementia by the age of 60 years. DS is caused by an extra copy of the long arm of human chromosome 21 (Hsa21) and the consequent elevated levels of expression, due to dosage, of trisomic genes. Despite a worldwide incidence of one in 700-1,000 live births, there are currently no pharmacological treatments available for ID or AD in DS. However, over the last several years, very promising results have been obtained with a mouse model of DS, the Ts65Dn. A diverse array of drugs has been shown to rescue, or partially rescue, DS-relevant deficits in learning and memory and abnormalities in cellular and electrophysiological features seen in the Ts65Dn. These results suggest that some level of amelioration or prevention of cognitive deficits in people with DS may be possible. Here, we review information from the preclinical evaluations in the Ts65Dn, how drugs were selected, how efficacy was judged, and how outcomes differ, or not, among studies. We also summarize the current state of human clinical trials for ID and AD in DS. Lastly, we describe the genetic limitations of the Ts65Dn as a model of DS, and in the preclinical testing of pharmacotherapeutics, and suggest additional targets to be considered for potential pharmacotherapies.
| S-EPMC4277121 | biostudies-literature
Project description:Polar Regions are unique and highly prolific ecosystems characterized by extreme environmental gradients. Photosynthetic autotrophs, the base of the food web, have had to adapt physiological mechanisms to maintain growth, reproduction and metabolic activity despite environmental conditions that would shut-down cellular processes in most organisms. High latitudes are characterized by temperatures below the freezing point, complete darkness in winter and continuous light and high UV in the summer. Additionally, sea-ice, an ecological niche exploited by microbes during the long winter seasons when the ocean and land freezes over, is characterized by large salinity fluctuations, limited gas exchange, and highly oxic conditions. The last decade has been an exciting period of insights into the molecular mechanisms behind adaptation of microalgae to the cryosphere facilitated by the advancement of new scientific tools, particularly "omics" techniques. We review recent insights derived from genomics, transcriptomics, and proteomics studies. Genes, proteins and pathways identified from these highly adaptable polar microbes have far-reaching biotechnological applications. Furthermore, they may provide insights into life outside this planet, as well as glimpses into the past. High latitude regions also have disproportionately large inputs into global biogeochemical cycles and are the region most sensitive to climate change.
| S-EPMC4009763 | biostudies-other
Project description:New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug resistant status epilepticus that often has a catastrophic outcome. A 30-year-old man of Somali origin presented with refractory status to a district general hospital. A clinical diagnosis of NORSE syndrome was made, and he was transferred to the regional epilepsy center for immunomodulatory treatment and consideration for cyclophosphamide treatment. After transfer to the regional epilepsy center, his repeat cerebrospinal fluid tested strongly positive for syphilis, indicating a diagnosis of neurosyphilis, and the patient was treated with high-dose intravenous (IV) benzylpenicillin. His status epilepticus abated 24 h later. New-onset refractory status epilepticus syndrome is a diagnosis of exclusion. Before instigation of potentially harmful neuromodulatory therapies, treatable causes such as neurosyphilis should be considered. We advocate the early transfer of refractory status patients to a specialist epilepsy center for both seizure management and cause determination.
| S-EPMC4388970 | biostudies-literature