Alissa M. D’Gama
A5017898544- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Epilepsy research and treatment
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Autism Spectrum Disorder Research
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Prenatal Screening and Diagnostics
- Metabolism and Genetic Disorders
- Congenital Heart Disease Studies
- Neonatal Respiratory Health Research
- BRCA gene mutations in cancer
- Glioma Diagnosis and Treatment
- Renal and related cancers
- Hedgehog Signaling Pathway Studies
- Genetic and Kidney Cyst Diseases
- Immunodeficiency and Autoimmune Disorders
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Testicular diseases and treatments
- Ethics and Legal Issues in Pediatric Healthcare
- Fetal and Pediatric Neurological Disorders
- Single-cell and spatial transcriptomics
Boston Children's Hospital
2015-2025
Harvard University
2016-2025
Boston Children's Museum
2019-2024
University College London
2024
SickKids Foundation
2024
Hospital for Sick Children
2024
Great Ormond Street Hospital
2024
Broad Institute
2015-2023
Howard Hughes Medical Institute
2014-2023
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2018-2020
Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) human brain. We identified thousands SNVs by single-cell sequencing 36 neurons from cerebral cortex three normal individuals. Unlike germline and cancer SNVs, which are often caused errors replication, neuronal mutations appear reflect damage during active transcription. Somatic create nested lineage trees, allowing them be dated...
Although there is increasing recognition of the role somatic mutations in genetic disorders, prevalence neurodevelopmental disease and optimal techniques to detect mosaicism have not been systematically evaluated.Using a customized panel known candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) leukocyte-derived DNA samples from 158 persons including double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria...
Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are epileptogenic neurodevelopmental malformations caused by mutations in mTOR pathway genes. Deep sequencing of these genes FCD/HME brain tissue identified an etiology 27 66 cases (41%). Radiographically indistinguishable lesions somatic activating AKT3, MTOR, PIK3CA germline loss-of-function DEPDC5, NPRL2, TSC1/2, including TSC2 isolated HME demonstrating a "two-hit" model. Mutations the same gene cause disease continuum from FCD...
Focal malformations of cortical development, including focal dysplasia (FCD) and hemimegalencephaly (HME), are important causes intractable childhood epilepsy. Using targeted exome sequencing on DNA from resected brain samples nonbrain 53 patients with FCD or HME, we identified pathogenic germline mosaic mutations in multiple PI3K/AKT pathway genes 9 patients, a likely variant 1 additional patient. Our data confirm the association DEPDC5 sporadic but also implicate this gene for first time...
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 schizophrenia, and 59 autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, had 20 60 detectable single-nucleotide mutations, but ~6% harbored hundreds mutations. Hypermutability was associated age damaging in genes implicated cancers and, some brains, reflected vivo clonal expansions. Somatic duplications, likely arising during development, were found ~5% normal...
Importance Genomic advances inform our understanding of epilepsy and can be translated to patients as precision diagnoses that influence clinical treatment, prognosis, counseling. Objective To delineate the genetic landscape pediatric utility for with epilepsy. Design, Setting, Participants This cohort study used phenotypic data from medical records treating clinicians at a hospital identify unexplained pediatric-onset Exome sequencing was performed 522 available biological parents, were...
Somatic mosaic variants contribute to focal epilepsy, with often present only in brain tissue and not blood or other samples typically assayed for genetic testing. Thus, analysis epilepsy has been limited patients drug-resistant who undergo surgical resection have resected available. Stereo-EEG (sEEG) become part of the evaluation many sEEG electrodes provide a potential source small amounts brain-derived DNA. We aimed identify, validate, assess distribution deleterious epilepsy-associated...
Abstract Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment novel conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians families is unclear. We identified reports published from 2017 2021 10 genetics journals Mendelian disorders. adjudicated the quality detail via 46 questions pertaining six priority domains: (I) Development, cognition, mental health;...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...