Matthew E. Hurles

A 4,000-year genomic history of Bantu speakers from the Congo rainforest

This study uses genomic data from ancient and present-day individuals to trace the 4,000-year demographic history of Bantu speakers in the Congo rainforest, revealing early dispersals and a population crisis.

Incompletely penetrant protein-truncating variants confer developmental disorder risk through partial reductions in gene expression

The paper shows inherited protein-truncating variants contribute to developmental disorders through partial gene expression loss, affecting ~20% of children with such variants.

Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants

The paper imputes fluid intelligence scores in a large cohort, reducing ascertainment bias and increasing power to detect genetic associations with common and rare variants.

The Contribution of Common and Rare Genetic Variation to Emotional and Behavioural Symptoms in Childhood and Adolescence

This study examines the genetic contributions to emotional and behavioural symptoms in childhood and adolescence using common and rare variants from two large cohorts.

Mutation timing, accumulation and selection in the male germline shape inheritance risk for developmental disorders

The paper investigates how mutation timing, accumulation, and selection in the male germline influence the risk of developmental disorders through de novo mutations.

Copy Number Variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders, the DDD-Africa study

The paper demonstrates that integrating CNV detection into exome sequencing analysis improves diagnostic yield for developmental disorders in the DDD-Africa cohort by 8.3% without additional costs.

Using somatic data to aid germline clinical variant interpretation in developmental disorders

This paper uses somatic mutation data to improve the classification of germline variants in developmental disorders by identifying genes where somatic and germline mechanisms are concordant.

Investigating the Interplay Between Prematurity and Genetic Variation in the Context of Rare Developmental Disorders

The paper examines how prematurity interacts with genetic variation in rare developmental disorders, finding independent and additive effects on phenotypic severity and identifying genetic contributions to preterm birth risk.

Sperm sequencing reveals extensive positive selection in the male germline

This study uses sperm sequencing to show that positive selection in the male germline leads to a higher risk of disease-causing mutations in offspring.

Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex

This study identifies cell-type-specific DNA methylation dynamics in the human cortex across development, highlighting prenatal periods as critical for epigenomic plasticity and linking changes to neurodevelopmental disorders.

Sex Differences in Human Brain Structure at Birth

The paper examines sex differences in brain structure at birth in newborns, finding larger brain volumes in males and specific regional differences in gray and white matter volumes between sexes.

The differential effects of common and rare genetic variants on cognitive performance across development

The paper examines how common and rare genetic variants affect cognitive performance across childhood and adolescence, finding age-related changes in their effects and differences in their impact across the phenotype distribution.

Substantial role of rare inherited variation in individuals with developmental disorders

The paper investigates the role of rare inherited coding variants in developmental disorders by analyzing family and case/control data, finding significant burdens of damaging variants and estimating their population attributable risk.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

Deciphering the role of germline complex de novo structural variations in rare disorders

This study identifies de novo structural variants in a large cohort of rare disease patients, highlighting their prevalence and potential pathogenicity.

Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions

This study investigates how common genetic variants contribute to risk for rare neurodevelopmental conditions and examines indirect genetic effects through parental non-transmitted alleles.

Detection and characterisation of copy number variants from exome sequencing in the DDD study

The paper evaluates CNV detection from exome sequencing in the DDD study, finding it has higher sensitivity than low-resolution CMA and comparable sensitivity to exon-resolution CMA.

Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation

The paper uses saturation genome editing to assess DDX3X variants' functional impact, identifies pathogenic variants for neurodevelopmental disorders, and develops a classifier outperforming existing tools.

Federated analysis of the contribution of recessive coding variants to 29,745 developmental disorder patients from diverse populations

The paper quantifies the contribution of recessive coding variants to developmental disorders in diverse populations, identifying novel genes and highlighting challenges in interpreting missense variants.

Rare genetic variants impact muscle strength

This study identifies six genes associated with hand grip strength using rare protein-coding variants in 340,319 individuals and shows additive effects with common variants.

The impact of rare protein coding genetic variation on adult cognitive function

This study identifies eight genes associated with adult cognitive function through rare coding variants and shows how KDM5B dosage affects cognitive traits in mice and humans.

Investigating the role of common cis-regulatory variants in modifying penetrance of putatively damaging, inherited variants in severe neurodevelopmental disorders

The paper investigates whether common cis-regulatory variants modify the penetrance of rare damaging coding variants in neurodevelopmental disorders using transcriptome-wide association and cis-eQTL analysis.

Differentiation of human induced pluripotent stem cells into cortical neural stem cells

This paper describes a 14-day protocol to differentiate human iPSCs into cortical neural stem cells, validated through RNA-Seq and immunocytochemistry.

Detection of mosaic chromosomal alterations in children with severe developmental disorders recruited to the DDD study

The paper identifies mosaic chromosomal alterations in children with developmental disorders using SNP array data from the DDD study, finding that many are tissue-specific and undetectable in blood.

A minimal role for synonymous variation in human disease

The paper cautions against interpreting a yeast study claiming synonymous mutations are as disease-causing as nonsynonymous ones, given existing evidence for their predominant neutrality in humans.

IMPROVE-DD: Integrating Multiple Phenotype Resources Optimises Variant Evaluation in genetically determined Developmental Disorders

IMPROVE-DD integrates multiple phenotype data sources to improve variant evaluation in developmental disorders, showing better diagnostic accuracy and fewer false positives.

Defective X-gating caused by de novo gain-of-function mutations in KCNK3 underlies a developmental disorder with sleep apnea

The paper identifies de novo gain-of-function mutations in KCNK3 causing a developmental disorder with sleep apnea by disrupting X-gating of TASK-1 channels.

A cross-disorder dosage sensitivity map of the human genome

This study identifies 114 genome-wide significant rare CNV-disease associations across 30 neurological disorders, revealing 38 novel triplosensitive genes and developing a model to predict dosage sensitivity.

Optimising diagnostic yield in highly penetrant genomic disease

The paper reports diagnostic outcomes from a large-scale genomic study of developmental disorders, identifying factors that influence diagnostic success.

Mouse and cellular models of KPTN-related disorder implicate mTOR signalling in cognitive and progressive overgrowth phenotypes

The paper investigates KPTN-related disorder using mouse and human stem cell models, identifying mTOR pathway dysregulation as a key mechanism underlying cognitive and overgrowth phenotypes.