Current Issue : October - December Volume : 2020 Issue Number : 4 Articles : 5 Articles
Autism spectrum disorder (ASD) consists of a genetically heterogenous group of\nneurobehavioral disorders characterized by impairment in three behavioral domains including\ncommunication, social interaction, and stereotypic repetitive behaviors. ASD affects more than 1%\nof children inWestern societies, with diagnoses on the rise due to improved recognition, screening,\nclinical assessment, and diagnostic testing. We reviewed the role of genetic and metabolic factors\nwhich contribute to the causation of ASD with the use of new genetic technology. Up to 40 percent of\nindividuals with ASD are now diagnosed with genetic syndromes or have chromosomal abnormalities\nincluding small DNA deletions or duplications, single gene conditions, or gene variants and metabolic\ndisturbances with mitochondrial dysfunction. Although the heritability estimate for ASD is between\n70 and 90%, there is a lower molecular diagnostic yield than anticipated. A likely explanation may\nrelate to multifactorial causation with etiological heterogeneity and hundreds of genes involved\nwith a complex interplay between inheritance and environmental factors influenced by epigenetics\nand capabilities to identify causative genes and their variants for ASD. Behavioral and psychiatric\ncorrelates, diagnosis and genetic evaluation with testing are discussed along with psychiatric\ntreatment approaches and pharmacogenetics for selection of medication to treat challenging behaviors\nor comorbidities commonly seen in ASD. We emphasize prioritizing treatment based on targeted\nsymptoms for individuals with ASD, as treatment will vary from patient to patient based on diagnosis,\ncomorbidities, causation, and symptom severity....
The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein\n(FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological\nfunctions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140bp exon from\nthe intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and\nits underlying signaling pathways.\nResults: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal\nindividuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the\ngenomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic\nexpression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated\nprotein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in\nmGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed.\nConclusions: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal\nhealthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account\nfor the multiple functions of FMRP....
Praderâ??Willi syndrome (PWS) is a rare disorder caused by the loss of expression of genes\non the paternal copy of chromosome 15q11-13. The main molecular subtypes of PWS are the deletion\nof 15q11-13 and non-deletion, and differences in neurobehavioral phenotype are recognized between\nthe subtypes. This study aimed to investigate growth trajectories in PWS and associations between\nPWS subtype (deletion vs. non-deletion) and height, weight and body mass index (BMI). Growth data\nwere available for 125 individuals with PWS (63 males, 62 females), of which 72 (57.6%) had the\ndeletion subtype. There was a median of 28 observations per individual (range 2-85), producing\n3565 data points distributed from birth to 18 years of age. Linear mixed models with cubic splines,\nsubject-specific random effects and an autoregressive correlation structure were used to model the\nlongitudinal growth data whilst accounting for the nature of repeated measures. Height was similar\nfor males in both PWS subtypes, with non-deletion females being shorter than deletion females\nfor older ages. Weight and BMI were estimated to be higher in the deletion subtype compared\nto the non-deletion subtype, with the size of difference increasing with advancing age for weight.\nThese results suggest that individuals with deletion PWS are more prone to obesity....
The ubiquitin E3 ligase RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes through different targets, including spinal cord patterning and the development of the cerebellum and the locus coeruleus. Here, we explored the effects of loss of ZC4H2 and RNF220 on the proliferation and differentiation of neural stem cells (NSCs) derived from mouse embryonic cortex. We showed that loss of either ZC4H2 or RNF220 inhibits the proliferation and promotes the differentiation abilities of NSCs in vitro. RNA-Seq profiling revealed 132 and 433 differentially expressed genes in the...................
Background: To test and introduce effective and less toxic breast cancer (BC) treatment\nstrategies, animal models, including murine BC cell lines, are considered as perfect platforms.\nStrikingly, the knowledge on the genetic background of applied BC cell lines is often sparse though\nurgently necessary for their targeted and really justified application. Methods: In this study,\nwe performed the first molecular cytogenetic characterization for three murine BC cell lines C-127I,\nEMT6/P and TA3 Hauschka. Besides fluorescence in situ hybridization-banding, array comparative\ngenomic hybridization was also applied. Thus, overall, an in silico translation for the detected\nimbalances and chromosomal break events in the murine cell lines to the corresponding homologous\nimbalances in humans could be provided. The latter enabled a comparison of the murine cell line with\nhuman BC cytogenomics. Results: All three BC cell lines showed a rearranged karyotype at different\nstages of complexity, which can be interpreted carefully as reflectance of more or less advanced tumor\nstages. Conclusions: Accordingly, the C-127I cell line would represent the late stage BC while the cell\nlines EMT6/P and TA3 Hauschka would be models for the premalignant or early BC stage and an\nearly or benign BC, respectively. With this cytogenomic information provided, these cell lines now\ncan be applied really adequately in future research studies....
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