William M. Brandler
A5071679444- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Reading and Literacy Development
- Hemispheric Asymmetry in Neuroscience
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetic Associations and Epidemiology
- Genetics and Physical Performance
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Children's Physical and Motor Development
- Animal Genetics and Reproduction
- Prenatal Screening and Diagnostics
- Reproductive Biology and Fertility
- Assisted Reproductive Technology and Twin Pregnancy
- Comparative Animal Anatomy Studies
- Science Education and Perceptions
- Cognitive and developmental aspects of mathematical skills
- Dermatoglyphics and Human Traits
Exact Sciences (United States)
2024
University of California, San Diego
2015-2019
Human Longevity (United States)
2018
University of Oxford
2013-2016
Centre for Human Genetics
2010-2016
Genomics (United Kingdom)
2013-2015
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...
Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis not well understood. Here we report genome-wide association study for quantitative measure relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10−7), located within PCSK6. Two independent cohorts RD show same trend, minor allele conferring greater right-hand skill. Meta-analysis all three samples significant (n...
Reading and language abilities are heritable traits that likely to share some genetic influences with each other. To identify pleiotropic variants affecting these traits, we first performed a genome‐wide association scan (GWAS) meta‐analysis using three richly characterized datasets comprising individuals histories of reading or problems, their siblings. GWAS was in total 1862 participants the principal component computed from several quantitative measures reading‐ language‐related...
Abstract Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development comorbidity conditions like attention-deficit hyperactivity disorder (ADHD), depression, anxiety. DD characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, phonology. To investigate genetic basis DD, we conducted a genome-wide association study (GWAS) these skills within largest studies available, nine...
While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)-present in some but not all cells-remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering at loci recurrently mutated clonal blood disorders. Likely early-developmental were more common (0.91%) than controls (0.51%, p = 2.68e-4), with recurrent deletions exons 1-5
Structural variation (SV) detection from short-read whole genome sequencing is error prone, presenting significant challenges for population or family-based studies of disease.Here, we describe SV2, a machine-learning algorithm genotyping deletions and duplications paired-end data. SV2 can rapidly integrate variant calls multiple structural discovery algorithms into unified call set with high accuracy capability to detect de novo mutations.SV2 freely available on GitHub...
Aim Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific impairment ( SLI ) dyslexia do not routinely undergo cytogenetic analysis. We assess frequency sex in dyslexia. Method Genome‐wide single nucleotide polymorphism genotyping was performed three sample sets: a clinical cohort speech and deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), replication , from both epidemiological samples (209 139 70 17 set...
We recently reported the association of PCSK6 gene with handedness through a quantitative genome-wide study (GWAS; P < 0.5 × 10−8) for relative hand skill measure in individuals dyslexia. activates Nodal, morphogen involved regulating left–right body axis determination. Therefore, GWAS data suggest that biology underlying patterning structural asymmetries may also contribute to behavioural laterality, e.g. handedness. The is further supported by an independent reporting variable number...
Abstract Genomic copy number variants (CNVs) have been strongly implicated in the etiology of schizophrenia (SCZ). However, apart from a small risk variants, elucidation CNV contribution to has difficult due rarity alleles, all occurring less than 1% cases. We sought address this obstacle through collaborative effort which we applied centralized analysis pipeline SCZ cohort 21,094 cases and 20,227 controls. observed global enrichment burden (OR=1.11, P=5.7e −15 ), persisted after excluding...
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...
Abstract Developmental dyslexia (DD) is one of the most prevalent learning disorders among children and characterized by deficits in different cognitive skills, including reading, spelling, short term memory others. To help unravel genetic basis these we conducted a Genome Wide Association Study (GWAS), nine cohorts reading-impaired typically developing European ancestry, recruited across countries (N=2,562-3,468). We observed genome-wide significant effect (p<1×10 −8 ) on rapid...
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...
Abstract Somatic variant calling involves the identification of genomic alterations that occur in somatic cells, requiring deep coverage to enable high sensitivity for low-frequency variants. Characterizing variants across entire genome therefore benefits from novel cost-efficient sequencing platforms, such as UG100. Here, we present optimization tools short and structural on WGS WES data For variants, optimized DeepVariant (DV) using matched tumor-normal sample pairs, improving both...
Abstract Motivation Structural Variation (SV) detection from short-read whole genome sequencing is error prone, presenting significant challenges for population or family-based studies of disease. Results Here we describe SV 2 , a machine-learning algorithm genotyping deletions and duplications paired-end data. can rapidly integrate variant calls multiple structural discovery algorithms into unified call set with high accuracy capability to detect de novo mutations. Availability...