A5040889865- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Autism Spectrum Disorder Research
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Prenatal Screening and Diagnostics
- Health, Environment, Cognitive Aging
- Congenital Heart Disease Studies
- Coronary Artery Anomalies
- CRISPR and Genetic Engineering
- Healthcare Systems and Public Health
- Virology and Viral Diseases
- Animal Genetics and Reproduction
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Reproductive Biology and Fertility
- Chromatin Remodeling and Cancer
- Bioinformatics and Genomic Networks
- Chromosomal and Genetic Variations
University of California, San Diego
2015-2024
Maastricht University
2023
University of California, Los Angeles
2023
California University of Pennsylvania
2023
Centre Hospitalier Universitaire Sainte-Justine
2023
Cardiff University
2023
UC San Diego Health System
2021
Inherited variation contributes to autism About one-quarter of genetic variants that are associated with spectrum disorder (ASD) due de novo mutations in protein-coding genes. Brandler et al. wanted determine whether changes noncoding regions the genome autism. They applied whole-genome sequencing ∼2600 families at least one affected child. Children ASD had inherited structural from their father. Regulatory some specific genes were disrupted among multiple families, supporting idea a...
A copy-number variant (CNV) of 16p11.2 encompassing 30 genes is associated with developmental and psychiatric disorders, head size, body mass. The genetic mechanisms that underlie these associations are not understood. To determine the influence on development, we investigated effects CNV craniofacial structure in humans model organisms. We show deletion duplication have "mirror" specific features conserved between human rodent models CNV. By testing dosage individual shape mandible...
Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions duplications associated neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying computerized assessment, Penn Computerized Neurocognitive Battery (CNB), administered in multi-site study...
Abstract The genetic etiology of autism spectrum disorder (ASD) is multifactorial with contributions from rare variants, polygenic risk, and sex. How combinations factors determine risk for ASD unclear. In 11,313 families (N = 37,375 subjects), we investigated the effects individually in combination. We show that liability differs by sex, females having a greater load, males lower threshold as evident negative correlation risk. Multiple were associated differing sets behavioral traits...
Abstract The genetic architecture of autism spectrum disorder (ASD) is known to consist contributions from gene-disrupting de novo mutations and common variants modest effect. We hypothesize that the unexplained heritability ASD also includes rare inherited with intermediate effects. investigated genome-wide distribution functional impact structural (SVs) through whole genome analysis ( ≥ 30X coverage) 3,169 subjects 829 families affected by ASD. Genes are intolerant inactivating in exome...
Summary De novo genetic mutations represent a major contributor to pediatric disease, including autism spectrum disorders (ASD), congenital heart and muscular dystrophies 1,2 , but there are currently no methods prevent or predict them. These classically thought occur either at low levels in progenitor cells the time of fertilization 1,3 often assigned risk recurrence siblings 4,5 . Here, we directly assess presence de paternal sperm discover abundant, germline-restricted mosaicism. From...
Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are among the most common rare genetic disorders associated with significant risk for neuropsychiatric across lifespan. Microdeletions duplications in these neurocognitive deficits, yet there few studies comparing groups using same measures. We address this gap a prospective international collaboration applying computerized assessment. The Penn Computerized Neurocognitive Battery (CNB) was administered...
Abstract A copy number variant (CNV) of 16p11.2, which encompasses 30 genes, is associated with developmental and psychiatric disorders, head size body mass. The genetic mechanisms that underlie these associations are not understood. To elucidate the effects genes on development, we exploited quantitative CNV craniofacial structure in humans model organisms. We show reciprocal deletion duplication 16p11.2 have characteristic “mirror” features conserved human, rat mouse. By testing gene...
Abstract Genetic studies of Autism Spectrum Disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment structural variation (SV) has been restricted by the coarse resolution current approaches. By applying a custom pipeline for SV discovery, genotyping assembly genome sequencing 235 subjects, 71 cases, 26 sibling controls their parents, we present an atlas 1.2 million SVs (5,213/genome), comprising 11 different classes. We demonstrate...
A copy number variant (CNV) of 16p11.2, which encompasses 30 genes, is associated with developmental and psychiatric disorders, head size body mass. The genetic mechanisms that underlie these associations are not understood. To elucidate the effects genes on development, we exploited quantitative CNV craniofacial structure in humans model organisms. We show reciprocal deletion duplication 16p11.2 have characteristic “mirror” features conserved human, rat mouse. By testing gene dosage shape...