Diane P. Genereux
A5053858033- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Autism Spectrum Disorder Research
- Genetic diversity and population structure
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Genetic Syndromes and Imprinting
- Obsessive-Compulsive Spectrum Disorders
- COVID-19 Clinical Research Studies
- Bat Biology and Ecology Studies
- Virology and Viral Diseases
- Genomic variations and chromosomal abnormalities
- SARS-CoV-2 and COVID-19 Research
- Evolution and Paleontology Studies
- Wildlife Ecology and Conservation
- Marine animal studies overview
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- Genetic Associations and Epidemiology
- Human-Animal Interaction Studies
- Developmental Biology and Gene Regulation
- Animal Vocal Communication and Behavior
- Veterinary Oncology Research
Broad Institute
2016-2024
University of Massachusetts Chan Medical School
2016-2023
Massachusetts Institute of Technology
2016-2022
University of Vienna
2022
Harvard University
2016-2017
University of Washington
2005-2013
Westfield State University
2012-2013
University of Chicago
2010
University of Cambridge
2010
University of Nottingham
2010
Significance The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, a major pandemic that threatens millions human lives and global economy. We identified large number mammals can potentially be infected by SARS-CoV-2 via their ACE2 proteins. This assist identification intermediate hosts for hence reduce opportunity future outbreak COVID-19. Among species we found with highest risk infection are wildlife endangered species. These represent an...
Abstract New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements third-generation technologies 1–3 . For example, the number of vertebrate currently NCBI (National Center for Biotechnology Information) database 4 increased by more than 50% 1,485 year from July 2018 2019. In addition this influx different species, new human de novo 5 are being produced, which enable analysis not only small polymorphisms, but also complex,...
Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half...
Behavioral genetics in dogs has focused on modern breeds, which are isolated subgroups with distinctive physical and, purportedly, behavioral characteristics. We interrogated breed stereotypes by surveying owners of 18,385 purebred and mixed-breed genotyping 2155 dogs. Most traits heritable [heritability ( h 2 ) > 25%], admixture patterns reveal propensities. Breed explains just 9% variation individuals. Genome-wide association analyses identify 11 loci that significantly associated...
Annotating coding genes and inferring orthologs are two classical challenges in genomics evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method integrates structural gene annotation orthology inference. implements different paradigm orthologous loci, improves ortholog detection of conserved compared with state-of-the-art methods, handles even highly fragmented assemblies. scales...
The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis genetic variation across an alignment 241 mammal genome assemblies, addressing prior concerns regarding limited genomic sampling species. compared neutral genome-wide phylogenomic signals using concatenation coalescent-based approaches, interrogated chromosomes, analyzed extensive catalogs structural variants. Interordinal...
Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation,...
We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. found that although mammals resemble one another total and diversity, they show substantial differences with regard recent accumulation. This includes multiple expansion quiescence events across mammalian tree. Young TEs, particularly long interspersed elements, drive increases size, whereas DNA transposons are associated smaller genomes....
Human accelerated regions (HARs) are conserved genomic loci that evolved at an rate in the human lineage and may underlie human-specific traits. We generated HARs chimpanzee with automated pipeline alignment of 241 mammalian genomes. Combining deep learning chromatin capture experiments neural progenitor cells, we discovered a significant enrichment topologically associating domains containing variants change three-dimensional (3D) genome organization. Differential gene expression between...
Understanding the regulatory landscape of human genome is a long-standing objective modern biology. Using reference-free alignment across 241 mammalian genomes produced by Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million candidate cis-regulatory elements (cCREs) and 15.6 transcription factor binding sites (TFBSs). We identified 439,461 cCREs 2,024,062 TFBSs under constraint. Genes near constrained perform fundamental cellular processes, whereas genes...
Species persistence can be influenced by the amount, type, and distribution of diversity across genome, suggesting a potential relationship between historical demography resilience. In this study, we surveyed genetic variation single genomes 240 mammals that compose Zoonomia alignment to evaluate how effective population size (
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning...
The survival of a species depends on its capacity to adjust changing environmental conditions, and new stressors. Such new, anthropogenic stressors include the neonicotinoid class crop-protecting agents, which have been implicated in population declines pollinating insects, including honeybees (Apis mellifera). low-dose effects these compounds larval development physiological responses remained largely unknown. Over period 15 days, we provided syrup tainted with low levels (2 µg/L−1)...
The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). main receptor SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), now undergoing extensive scrutiny to understand routes transmission and sensitivity in different species. Here, we utilized a unique dataset 410 vertebrates, including 252 mammals, study cross-species conservation ACE2 its likelihood function as receptor. We designed five-category ranking score based on properties 25 amino acids important...
Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes syntenic relationships at 16 nodes along phylogeny. Three different reference genomes (human, sloth, cattle) phylogenetically distinct superorders were used assess bias in expand...
Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) are enriched for brain functions across genetic, epigenomic, transcriptomic datasets. Using massively parallel reporter assays six cell types, we discovered 800 hCONDELs conferring significant differences regulatory activity, half of which enhance rather than disrupt function....
Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (
Obsessive-compulsive disorder is a severe psychiatric linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding regulatory elements for 608 genes potentially involved obsessive-compulsive human, dog, mouse. Using new method that prioritizes likely functional variants, we compared 592 cases 560 controls found four strongly associated genes, validated larger cohort. NRXN1 HTR2A are enriched variants altering postsynaptic protein-binding domains....
Cytosine methylation is an epigenetic mechanism in eukaryotes that often associated with stable transcriptional silencing, such as X-chromosome inactivation and genomic imprinting. Aberrant patterns occur several inherited human diseases many cancers. To understand how methylated unmethylated states of cytosine residues are transmitted during DNA replication, we develop a population-epigenetic model dynamics. The informed by our observation de novo can on the daughter strand while leaving...
Abstract Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown experience horizontal TEs at what appears be a high rate compared with other mammals. We investigated the occurrence horizontally transferred (HT) DNA transposons involving bats. found over 200 putative HT within bats; 16 were shared across distantly related mammalian clades, 2 fish two lizard species. Our...
Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly complex diseases like cancer. Comprehensive genomic annotation regulatory elements active in healthy canine tissues is crucial both identifying candidate causal variants designing functional studies needed to translate genetic associations into disease insight. Currently, geneticists rely primarily on annotations human or mouse genome that have been remapped dog, approach misses...
Abstract Cactus, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions duplicated sequence. We describe progressive extensions Cactus that enable tens thousands large vertebrate genomes while maintaining high quality. show is capable scaling hundreds beyond by describing results from an over 600 amniote which our knowledge largest yet created....
Although thousands of genomic regions have been associated with heritable human diseases, attempts to elucidate biological mechanisms are impeded by a general inability discern which positions functionally important. Evolutionary constraint is powerful predictor function that agnostic cell type or disease mechanism. Here, single base phyloP scores from the whole genome alignment 240 placental mammals identified 3.5% as significantly constrained, and likely functional. We compared these...
The prevalence of tickborne diseases worldwide is increasing virtually unchecked due to the lack effective control strategies. transmission dynamics pathogens are influenced by tick microbiome, co-infection with other pathogens, and environmental features. Understanding this complex system could lead new strategies for pathogen control, but will require large-scale, high-resolution data. Here, we introduce Project Acari, a citizen science-based project assay, at single-tick resolution,...