scholarly journals Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism

2021 ◽  
Author(s):  
Michael V. Lombardo ◽  
Elena Maria Busuoli ◽  
Laura Schreibman ◽  
Aubyn C. Stahmer ◽  
Tiziano Pramparo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Outcome ◽  
Early Intervention ◽  
Developmental Change ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Time In Treatment ◽  
Pre Treatment ◽  
Blood Leukocyte ◽  
The Impact

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

scholarly journals Pre-treatment clinical behavioral and blood leukocyte gene expression patterns predict rate of change in response to early intervention in autism

2020 ◽  
Author(s):  
Michael V. Lombardo ◽  
Elena Maria Busuoli ◽  
Laura Schreibman ◽  
Aubyn C. Stahmer ◽  
Tiziano Pramparo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Outcome ◽  
Early Intervention ◽  
Expression Patterns ◽  
Rate Of Change ◽  
Biological Factor ◽  
Gene Expression Patterns ◽  
Pre Treatment ◽  
Blood Leukocyte ◽  
The Impact

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., < 24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predicts 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predicts rate of skill growth, accounting for 13% of the variance treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism post-mortem cortical tissue, and are normatively highly expressed in variety of subcortical and cortical areas important for social-communication and language development. This work indicates for the first time that gene expression can predict the rate of early intervention response and that a key biological factor linked to treatment outcome could be the susceptibility for epigenetic change via mechanisms such as histone acetylation.

scholarly journals Toxoplasma infection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Low Grade ◽  
Cocaine Exposure ◽  
Multiple Testing Correction ◽  
The Impact

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.

The impact of α-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice

2004 ◽  
Vol 36 (8) ◽  
pp. 1043-1057 ◽  
Author(s):  
Cheol-Koo Lee ◽  
Thomas D Pugh ◽  
Roger G Klopp ◽  
Jode Edwards ◽  
David B Allison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Span ◽  
Caloric Restriction ◽  
Lipoic Acid ◽  
Coenzyme Q10 ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
The Impact

scholarly journals Peripheral Blood Leukocyte Gene Expression Patterns and Metabolic Parameters in Habitually Snoring and Non-Snoring Children with Normal Polysomnographic Findings

SLEEP ◽  
2011 ◽  
Vol 34 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Abdelnaby Khalyfa ◽  
Sina A. Gharib ◽  
Jinkwan Kim ◽  
Oscar Sans Capdevila ◽  
Leila Kheirandish-Gozal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Peripheral Blood Leukocyte ◽  
Metabolic Parameters ◽  
Gene Expression Patterns ◽  
Blood Leukocyte

scholarly journals Cis-regulatory divergence underpins the evolution of C3-C4 intermediate photosynthesis in Moricandia

2021 ◽  
Author(s):  
Meng-Ying Lin ◽  
Urte Schlueter ◽  
Benjamin Stich ◽  
Andreas P.M. Weber
Keyword(s):  
Gene Expression ◽  
C4 Photosynthesis ◽  
Expression Patterns ◽  
Transcript Level ◽  
F1 Hybrids ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Promoter Regions ◽  
Specific Gene Expression ◽  
The Impact

Altered transcript abundances and cell specific gene expression patterns that are caused by regulatory divergence play an important role in the evolution of C4 photosynthesis. How these altered gene expression patterns are achieved and whether they are driven by cis- or trans-regulatory changes is mostly unknown. To address this question, we investigated the regulatory divergence between C3 and C3-C4 intermediates, using allele specific gene expression (ASE) analyses of Moricandia arvensis (C3-C4), M. moricandioides (C3) and their interspecific F1 hybrids. ASE analysis on SNP-level showed similar relative proportions of regulatory effects among hybrids: 36% and 6% of SNPs were controlled by cis-only and trans-only changes, respectively. GO terms associated with metabolic processes and the positioning of chloroplast in cells were abundant in transcripts with cis-SNPs shared by all studied hybrids. Transcripts with cis-specificity expressed bias toward the allele from the C3-C4 intermediate genotype. Additionally, ASE evaluated on transcript-level indicated that ~27% of transcripts show signals of ASE in Moricandia hybrids. Promoter-GUS assays on selected genes revealed altered spatial gene expression patterns, which likely result from regulatory divergence in their promoter regions. Assessing ASE in Moricandia interspecific hybrids contributes to the understanding of early evolutionary steps towards C4 photosynthesis and highlights the impact and importance of altered transcriptional regulations in this process.

scholarly journals Comparative transcriptomic profiling of myxomatous mitral valve disease in the Cavalier King Charles Spaniel

2020 ◽  
Author(s):  
Brendan Corcoran ◽  
Greg Markby ◽  
Vicky Macrae ◽  
Kim Summers
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Mitral Valve ◽  
Mitral Valve Disease ◽  
Expression Patterns ◽  
Valve Disease ◽  
Gene Expression Patterns ◽  
Transcriptomic Profiling ◽  
Cavalier King Charles Spaniel ◽  
The Impact

Abstract Background. All dogs develop myxomatous mitral valve disease by the end of their life, but the Cavalier King Charles Spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in CKCS diseased mitral valves compared to valves from non-CKCS dogs. Results. Gene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, CKCS diseased valves and diseased valves from other breeds; the latter were more similar to the normal valves than were the CKCS valves. CKCS valve gene expression patterns were quite different from those in the other dogs, both affected and normal. Patterns in all diseased valves (CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS valves compared to normal) and MEF2C pathway activation (CKCS valves compared to non-CKCS) had the strongest association with the gene changes. A large number of DEGs in the CKCSs were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2. Conclusion. Transcriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

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