Publications by authors named "Brett Trost"

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

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Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.

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The muskox (Ovibos moschatus), an integral component and iconic symbol of arctic biocultural diversity, is under threat by rapid environmental disruptions from climate change. We report a chromosomal-level haploid genome assembly of a muskox from Banks Island in the Canadian Arctic Archipelago. The assembly has a contig N50 of 44.

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Autism Spectrum Disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as , , and .

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This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges.

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Aim: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes.

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We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.

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Many rare genetic variants are associated with the risk of atypical neurodevelopmental trajectories. In this study, we report a patient with developmental delay, autistic traits and multiple congenital anomalies, including congenital heart anomalies and orofacial cleft, with a 0.832 Mb de novo deletion of the 16p13.

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Article Synopsis
  • Cardiomyopathy is a diverse heart condition often linked to genetic factors, with over 50% of cases having unknown genetic causes.
  • This study analyzes genetic data from 1,216 individuals with cardiomyopathy to investigate the role of rare tandem repeat expansions (TREs) in the disease.
  • The research reveals that these rare TREs are more common in affected individuals, particularly in specific genes that may be silenced through DNA methylation, influencing heart function.
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The genetic correlates of extreme impulsive violence are poorly understood, and there have been few studies that have characterized a large group of affected individuals both clinically and genetically. We performed whole exome sequencing (WES) in 290 males with the life-course-persistent, extremely impulsively violent form of antisocial personality disorder (APD) and analyzed the spectrum of rare protein-truncating variants (rPTVs). Comparisons were made with 314 male controls and publicly available genotype data.

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Article Synopsis
  • Autism Spectrum Disorder (ASD) has a significant male-to-female ratio (~4:1) and is marked by social and communication difficulties, restricted interests, and repetitive behaviors.
  • Disruption of the Xp22.11 genetic region has been linked to ASD, highlighting the importance of specific genes and long noncoding RNAs in understanding the condition.
  • In a study of 31 individuals with ASD, rare genetic variants were found predominantly in a specific gene, suggesting a connection between this gene and ASD, which could influence future clinical testing and animal model research.
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Autism spectrum disorder (ASD) comprises a group of complex neurodevelopmental features seen in many different forms due to variable causes. Highly impactful ASD-susceptibility genes are involved in pathways associated with brain development, chromatin remodeling, and transcription regulation. In this study, we investigate a proband with complex ASD.

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Article Synopsis
  • Autism spectrum disorder (ASD) prevalence in Qatar is around 1.1%, but genetic research in the region is limited; the BARAKA-Qatar Study aims to create a biorepository for ASD families to facilitate future research.
  • * Whole-genome sequencing (WGS) analysis of 100 families revealed potentially pathogenic variants in 27% of them, with a notable contribution from dominant and homozygous variants, particularly in consanguineous families.
  • * The study also identified 28 new candidate genes related to ASD, emphasizing the importance of including under-represented populations in genetic research to understand the disorder better.
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Background: We present genomic and phenotypic findings of a transgenerational family consisting of three male offspring, each with a maternally inherited distal 220 kb deletion at locus 16p11.2 (BP2-BP3). Genomic analysis of all family members was prompted by a diagnosis of autism spectrum disorder (ASD) in the eldest child, who also presented with a low body mass index.

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Article Synopsis
  • - The study examined gene copy number variation (CNV) in a large group of 7,100 children and youth, focusing on its impact on mental health, cognitive functioning, and physical health.
  • - Clinically relevant CNVs were found in 3.9% of participants and were linked to higher ADHD traits, cognitive deficits, and increased occurrence of specific mental health diagnoses like ADHD, autism spectrum disorder, and learning disorders.
  • - The research highlights the role of rare genetic deletions in brain-related gene sets, suggesting they contribute to ADHD characteristics, and sets a baseline for understanding genetic factors in mental health issues among youth during a growing crisis.
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There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants.

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Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia.

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Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This increases complexity and time burden, potentially resulting in missed genetic diagnoses.

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Article Synopsis
  • Full understanding of autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS), highlighted by the latest Autism Speaks MSSNG resource that includes data from over 11,000 individuals.
  • The study found ASD-associated rare genetic variants in about 14% of individuals with ASD, examining data from MSSNG and the Simons Simplex Collection, which suggests similar prevalence in both datasets.
  • The identified variants were mostly nuclear (98%) with a small fraction being mitochondrial, and the research aims to help explore genetic links to ASD traits and identify causes for the 85% of ASD cases that currently lack identified genetic causes.
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  • Research identifies distinct genetic subtypes of autism spectrum disorder (ASD) by analyzing physical traits, categorizing 325 Canadian children with ASD into dysmorphic and nondysmorphic groups.
  • A novel genome-wide rare variant score (GRVS) was developed to assess genetic variants, revealing that children with dysmorphic ASD exhibit significantly higher GRVS than those without physical anomalies.
  • Additional analysis using a polygenic transmission test showed that common ASD variants are more prevalent in nondysmorphic probands, supporting a new classification approach based on morphology to guide treatment strategies.
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Like humans, canine lymphomas are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make canines excellent models to study MDR mechanisms. Insulin-sensitizers have been shown to reduce the incidence of cancer in humans prescribed them, and we previously demonstrated that they also reverse and delay MDR development in vitro.

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We have identified active enhancers in the mouse cerebellum at embryonic and postnatal stages which provides a view of novel enhancers active during cerebellar development. The majority of cerebellar enhancers have dynamic activity between embryonic and postnatal development. Cerebellar enhancers were enriched for neural transcription factor binding sites with temporally specific expression.

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We report a chromosomal-level genome assembly of a male North American wolverine (Gulo gulo luscus) from the Kugluktuk region of Nunavut, Canada. The genome was assembled directly from long-reads, comprising: 758 contigs with a contig N50 of 36.6 Mb; contig L50 of 20; base count of 2.

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Article Synopsis
  • Tandem repeat expansions (TREs) are linked to neurological diseases, but their role in schizophrenia was previously unknown.
  • Researchers found that individuals with schizophrenia have more TREs near important gene regions compared to those without psychiatric issues.
  • These rare TREs are located in genes associated with schizophrenia and may disrupt normal gene functioning, contributing to the complex genetic makeup of the disorder.
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Autism spectrum disorder (ASD) describes a complex and heterogenous group of neurodevelopmental disorders. Whole genome sequencing continues to shed light on the multifactorial etiology of ASD. Dysregulated transcriptional pathways have been implicated in neurodevelopmental disorders.

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