Aravinda Chakravarti

A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism

The paper identifies noncoding MECP2 variants that cause male-biased autism by disrupting CRE activity and reducing MECP2 expression.

Sex Steroid Hormone Signaling Tunes Metabolic and Neuronal Programs in Human Cortical Development

The paper investigates how sex steroid hormones influence metabolic and neuronal programs during human cortical development using single-cell RNA-seq and hormone exposure experiments.

BxbI-mediated insertion of a 77kb human RET sensitive haplotype into the mouse genome to generate a humanized model of Hirschsprung disease

This study inserts a human RET haplotype into mice to model Hirschsprung disease, finding that regulatory variants reduce RET expression and contribute to disease.

Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

This study shows that SOD1 trisomy disrupts ENS development and increases HSCR risk by reducing RET expression and altering glial states.

Sex differences in the developing human cortex intersect with genetic risk of neurodevelopmental disorders

The paper identifies sex-biased molecular vulnerabilities in the developing human cortex linked to neurodevelopmental disorders by integrating transcriptomic and epigenomic data with mutation analysis.

Massively parallel reporter assays identify functional enhancer variants at QT interval GWAS loci

The paper identifies functional enhancer variants at QT interval GWAS loci using MPRA and predicts their impact on cardiac gene expression.

Joint disruption of Ret and Ednrb transcription drives cell fate reversal in the Enteric Nervous System in Hirschsprung disease

This study shows that reduced function alleles in Ret and Ednrb genes cause Hirschsprung disease by disrupting their gene regulatory network and leading to cell fate reversal in the enteric nervous system.

Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants

The paper assesses the functional impact of RET pathogenic variants in Hirschsprung disease by analyzing their effects on cell proliferation and migration in a neural crest-derived cell line.

Combined effects of Ret coding and enhancer loss-of-function alleles cause progressive loss of inhibitory motor neurons in the enteric nervous system

The paper investigates how a non-coding variant in a RET enhancer and a coding null allele together cause loss of inhibitory motor neurons in the enteric nervous system, leading to Hirschsprung disease.

The Role of de novo and Ultra-Rare Variants in Hirschsprung Disease (HSCR): Extended Gene Discovery for Risk Profiling of Patients

The paper identifies 19 risk genes for Hirschsprung Disease, including 15 novel candidates, showing ultra-rare variants contribute significantly to disease risk and severity.

Identification of the molecular components of enhancer-mediated gene expression variation in multiple tissues regulating blood pressure

The paper identifies genes regulating blood pressure by analyzing enhancer variants and integrating epigenomic data with genotype-phenotype associations across multiple tissues.

RET enhancer haplotype-dependent remodeling of the human fetal gut development program

The paper shows RET enhancer variants reduce gene expression and alter the fetal gut development program, potentially causing Hirschsprung disease through effects on neural crest cell proliferation.

Tissue-specific and tissue-agnostic effects of genome sequence variation modulating blood pressure

The paper identifies tissue-specific regulatory variants influencing blood pressure heritability using GWAS and gene expression data.

Cardiac muscle-restricted partial loss of Nos1ap expression has limited impact on electro- and echo-cardiographic features

The paper investigates the impact of partial NOS1AP loss in cardiac muscle on electrocardiographic features, finding no effect on QT interval but a small reduction in QRS interval.

Ret loss-of-function decreases enteric neural crest progenitor proliferation and restricts developmental fate potential during enteric nervous system development

This study shows that Ret loss-of-function in mouse embryos reduces enteric neural crest progenitor proliferation and limits neuronal fate potential during ENS development.

Interleukin-1 receptor antagonist gene (IL1RN) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2

This study identifies IL1RN variants associated with reduced cytokine release syndrome and mortality in male SARS-CoV-2 patients.

Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model

The paper introduces gkmQC, a sequence-based model to assess and refine chromatin accessibility data quality, improving peak calling and regulatory element alignment.

Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19

This study identifies IFN pathway lupus risk alleles associated with COVID-19 mortality and develops predictive models combining genetics and biomarkers.

Genome-wide pleiotropy analysis identifies novel blood pressure variants and improves its polygenic risk scores

This study identifies novel blood pressure variants through pleiotropy analysis and improves polygenic risk scores for hypertension and cardiovascular disease.

A multi-enhancer RET regulatory code is disrupted in Hirschsprung disease

The paper identifies 31 HSCR-associated variants in RET CREs, ten with differential enhancer activity and seven affecting RET expression, revealing an extensive regulatory code modulating HSCR risk.

Multiple, independent, common variants overlapping known and putative gut enhancers at RET, SEMA3 and NRG1 underlie Hirschsprung disease risk in European ancestry subjects

The paper identifies common noncoding variants at RET, SEMA3, and NRG1 loci associated with Hirschsprung disease risk in European ancestry individuals, showing cumulative effects on gene expression.

Sequence-based correction of barcode bias in massively parallel reporter assays

This paper introduces a sequence-based method to correct barcode bias in MPRA experiments, improving detection of functional regulatory variants and capturing post-transcriptional regulatory features.

Analysis of putative cis-regulatory elements regulating blood pressure variation

The paper identifies putative cis-regulatory elements associated with blood pressure traits using open chromatin and gene expression data, and identifies several candidate genes for further functional testing.

The gastrointestinal development ‘parts list’: transcript profiling of embryonic gut development in wildtype and Ret-deficient mice

The paper profiles RNA-seq data from wildtype and Ret-deficient mouse gut tissues during embryonic development to identify genetic programs involved in enteric nervous system formation and disease.

A Comprehensive Evaluation of the Genetic Architecture of Sudden Cardiac Arrest

This study evaluates the genetic architecture of sudden cardiac arrest through GWAS and Mendelian randomization, finding genetic correlations with CAD, height, BMI, and electrical instability traits.