Kathleen M. Morrill
A5089651119- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Human-Animal Interaction Studies
- Chromosomal and Genetic Variations
- Genetic diversity and population structure
- Evolution and Paleontology Studies
- Bat Biology and Ecology Studies
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Wildlife Ecology and Conservation
- Genetic Mapping and Diversity in Plants and Animals
- Marine animal studies overview
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- Autism Spectrum Disorder Research
- Animal Vocal Communication and Behavior
- Genomic variations and chromosomal abnormalities
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Neuroendocrine regulation and behavior
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- Developmental Biology and Gene Regulation
- Obsessive-Compulsive Spectrum Disorders
Broad Institute
2019-2024
University of Massachusetts Chan Medical School
2019-2023
Morningside College
2023
National Cancer Institute
2019
Cold Spring Harbor Laboratory
2016-2017
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum share both genetic underpinnings pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA DNA binding protein, is observed in the vast majority familial sporadic ALS cases ~40% FTLD cases, but cascade events leading to cell death not understood. We have expressed...
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...
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 (
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...
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...
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....
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...
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 (
Dire wolves (Aenocyon dirus) are extinct predators of Pleistocene North America. Although phenotypically similar to living (Canis lupus), dire have yet be placed confidently in the canid family tree. We generated 3.4x and 12.8x paleogenomes from two well-preserved dating > 13,000 72,000 years ago, estimated consensus species trees for these 10 species. Our results revealed that ~2/3 wolf ancestry is derived a lineage sister clade comprising gray wolf, coyote, dhole, remaining ~1/3 near...
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...
We reconstruct the phenotype of Balto, heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from Zoonomia alignment 240 mammals and 682 genomes dogs wolves 21st century. Balto shares just part his diverse ancestry with eponymous Siberian husky breed. Balto’s genotype predicts a combination coat features atypical modern breeds, slightly smaller stature. He had enhanced starch digestion compared Greenland compendium...
Abstract Current genetic research on obsessive-compulsive disorder (OCD) supports contributions to risk specifically from common single nucleotide variants (SNVs), along with rare coding SNVs and small insertion-deletions (indels). The contribution OCD copy number (CNVs), however, has not been formally assessed at a similar scale. Here we describe an analysis of CNVs called genotype array data in 2248 deeply phenotyped cases 3608 unaffected controls Sweden Norway. Cases carry elevated burden...
The characterization of immortalized canine osteosarcoma (OS) cell lines used for research has historically been based on phenotypic features such as cellular morphology and expression bone specific markers. With the increasing use these to investigate novel therapeutic approaches prior in vivo translation, a much more detailed understanding regarding genomic landscape is required ensure accurate interpretation findings. Here we report first whole genome eight OS lines, including single...
Summary Genetic elements in the bacteriophage λ immunity region contribute to stable maintenance and synchronous induction of integrated Escherichia coli prophage . There is a bistable switch between lysogenic lytic growth that orchestrated by CI Cro repressors acting on ( P L R ) RM promoters, referred as Switch. Other less well‐characterized phage include LIT promoter terminator, T IMM The repressed bacterial LexA protein lysogens. repressor, like inactivated during SOS response DNA...
Current knowledge of cancer genomics remains biased against noncoding mutations. To systematically search for regulatory mutations, we assessed mutations in conserved positions the genome under assumption that these are more likely to be functional than with low conservation. this end, use whole-genome sequencing data from International Cancer Genome Consortium and combined it evolutionary constraint inferred 240 mammals, identify genes enriched (NCCMs), nature. We compare medulloblastoma...
Abstract Evolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number reliance on human-referenced alignments. We explore the evolution placental mammals, including humans, through reference-free whole-genome alignment 240 protein-coding alignments for 428 species. estimate 10.7% human genome is evolutionarily constrained. resolve to single nucleotides, pinpointing positions, refine...