A5004149364- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- Genetic diversity and population structure
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Origins and Evolution of Life
- Genomics and Chromatin Dynamics
- Atherosclerosis and Cardiovascular Diseases
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Genomics and Rare Diseases
- Genetic Mapping and Diversity in Plants and Animals
- Intramuscular injections and effects
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Viral Infections and Immunology Research
- Genome Rearrangement Algorithms
- Advanced Software Engineering Methodologies
- Cell Adhesion Molecules Research
- Tendon Structure and Treatment
- CAR-T cell therapy research
- Machine Learning in Bioinformatics
- Molecular Biology Techniques and Applications
- Nematode management and characterization studies
University of Washington
2009-2024
Howard Hughes Medical Institute
2009-2024
Agilent Technologies (United States)
2007
University of Michigan
1993-1997
United States Department of Health and Human Services
1983
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little past two decades, because most genetic events initiate remain undiscovered. Whole-genome sequencing now possible at reasonable cost and timeframe to use approach for unbiased discovery tumour-specific somatic mutations alter protein-coding genes. Here we present results obtained from typical acute genome, its...
Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins treat human disease. Previously, in humans has been achieved by a cell-mediated ex vivo approach which cells from blood or tissue of patients are genetically modified laboratory and subsequently returned patient. To determine feasibility safety directly transferring genes into humans, clinical study was performed. The foreign major histocompatibility complex protein, HLA-B7, introduced HLA-B7-negative...
The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists a circular chromosome, linear and two plasmids. Extensive orthology nucleotide colinearity between genomes A. symbiont Sinorhizobium meliloti suggest recent evolutionary divergence. Their similarities include metabolic, transport, regulatory systems that promote survival in highly competitive rhizosphere; differences are apparent their structure virulence gene complement. Availability sequence will...
Selection acting on genomic functional elements can be detected by its indirect effects population diversity at linked neutral sites. To illuminate the selective forces that shaped hominid evolution, we analyzed distributions of human polymorphisms and sequence differences among five primate species relative to locations conserved features. Neutral in ancestral populations is substantially reduced near such features, resulting a surprisingly large genome average reduction due selection...
Improving on the gorilla genome Access to complete, high-quality genomes of nonhuman primates will also help us understand human biology. Gordon et al. used long-read sequencing technology improve data our close relative gorilla. Sequencing from a single individual decreased assembly fragmentation and recovered previously missed genes noncoding loci. Mapping short-read sequences additional gorillas helped reconstruct “pan” sequence documenting genetic variation. Comparison with revealed...
In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid genomes. By using assembly-based approach (SMRT-SV), systematically assessed each genome independently for structural variants (SVs) and indels resolving sequence structure 461,553 2 bp 28 kbp in length. We find that >89% these have been missed as part analysis 1000 Genomes Project even after adjusting common (MAF > 1%)....
A spotlight on great ape genomes Most nonhuman primate generated to date have been “humanized” owing their many gaps and the reliance guidance by reference human genome. To remove this humanizing effect, Kronenberg et al. assembled long-read of a chimpanzee, an orangutan, two humans compared them with previously gorilla This analysis recognized genomic structural variation specific particular lineages. Comparisons between chimpanzee cerebral organoids showed down-regulation expression genes...
A high-quality rhesus macaque genome Genome technology has improved substantially since the first full organismal genomes were generated. Applying new technology, Warren et al. refined of macaque, a model nonhuman primate. Long-read and other recent advances in sequencing applied to generate with far fewer gaps helped refine locations numbers repetitive elements. Furthermore, authors performed resequencing among populations identify genetic variability macaque. Thus, previously incomplete...
Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 in 41 human genomes. Approximately 85% of <2 kbp form by twin-priming during L1 retrotransposition; 80% the larger are balanced and affect twice as many nucleotides CNVs. Balanced show excess common variants, 72% flanked segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous...
We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, marmoset. identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes 136,932 regulatory elements, including most complete set human-specific differences. estimate that 819.47 Mbp or ∼27% genome has been affected by SVs across primate evolution. identify 1,607 structurally divergent...
Platelet-derived growth factor (PDGF) B chain induces cell proliferation in vitro and is associated with arterial lesions that cause cardiovascular disease. However, it has been difficult to document the biological response PDGF gene expression arteries vivo. To determine biologic effects of this vivo, we have introduced an eukaryotic vector plasmid encoding recombinant by direct transfer into porcine iliofemoral using DNA liposome complexes. The presence mRNA were confirmed polymerase...
Abstract Consed is a program for viewing and editing assemblies prepared by the Phrap assembly program. This unit presents general introduction to Consed. It also provides instructions identifying problem regions searching in Additional protocols describe creating tags, picking primers, correcting joins adding removing reads. Instructions are given use of Assembly View, predicting results restriction digestion, conjunction with PolyPhred, using Autofinish, as well procedure running Phred Phrap.
The recent introductions of low-cost, long-read, and read-cloud sequencing technologies coupled with intense efforts to develop efficient algorithms have made affordable, high-quality de novo sequence assembly a realistic proposition. result is an explosion new, ultracontiguous genome assemblies. To compare these genomes, we need robust methods for annotation. We describe the fully open source Comparative Annotation Toolkit (CAT), which provides flexible way simultaneously annotate entire...
Abstract The divergence of chimpanzee and bonobo provides one the few examples recent hominid speciation 1,2 . Here we describe a fully annotated, high-quality genome assembly, which was constructed without guidance from reference genomes by applying multiplatform genomics approach. We generate assembly in more than 98% genes are completely annotated 99% gaps closed, including resolution about half segmental duplications almost all full-length mobile elements. compare to those other great...
Diverse inbred mouse strains are important biomedical research models, yet genome characterization of many is fundamentally lacking in comparison with humans. In particular, catalogs structural variants (SVs) (variants ≥ 50 bp) incomplete, limiting the discovery causative alleles for phenotypic variation. Here, we resolve genome-wide SVs 20 genetically distinct mice long-read sequencing. We report 413,758 site-specific affecting 13% (356 Mbp) reference assembly, including 510 previously...
Among the potential nonviral vectors for human gene therapy are DNA–liposome complexes. In a recent clinical study, this delivery system has been utilized. report, novel cationic lipid, dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium (DMRIE), substituted into complex with dioleoyl phosphatidylethanolamine (DOPE), which both improves transfection efficiencies and allows increased doses of DNA to be delivered in vivo. The safety toxicity evaluated two species, mice pigs. efficacy...
The study and treatment of pulmonary diseases may be greatly facilitated by in vivo expression specific recombinant genes the vasculature lung parenchyma. To evaluate feasibility gene transfer to vasculature, cationic liposomes adenoviral vectors encoding a human placental alkaline phosphatase (hpAP) were delivered into artery 24 pigs percutaneous right heart catheterization. Pulmonary tissue was harvested within 20 minutes or 5, 14, 28 days later analyzed for expression. Five after exposure...
Abstract The chimpanzee is arguably the most important species for study of human origins. A key resource these studies a high-quality reference genome assembly; however, as with mammalian genomes, current iteration assembly highly fragmented. In (Pan_tro_2.1.4), sequence scattered across more then 183 000 contigs, incorporating than 159 gaps, genome-wide contig N50 51 Kbp. this work, we produce an extensive and diverse array sequencing datasets to rapidly assemble new that surpasses...
ABSTRACT To better understand the pattern of primate genome structural variation, we sequenced and assembled using multiple long-read sequencing technologies genomes eight nonhuman species, including New World monkeys (owl monkey marmoset), Old (macaque), Asian apes (orangutan gibbon), African ape lineages (gorilla, bonobo, chimpanzee). Compared to human genome, identified 1,338,997 lineage-specific fixed variants (SVs) disrupting 1,561 protein-coding genes 136,932 regulatory elements, most...
ABSTRACT The recent introductions of low-cost, long-read, and read-cloud sequencing technologies coupled with intense efforts to develop efficient algorithms have made affordable, high-quality de novo sequence assembly a realistic proposition. result is an explosion new, ultra-contiguous genome assemblies. To compare these genomes we need robust methods for annotation. We describe the fully open source Comparative Annotation Toolkit (CAT), which provides flexible way simultaneously annotate...
SUMMARY Diverse inbred mouse strains are among the foremost models for biomedical research, yet genome characterization of many has been fundamentally lacking in comparison to human genomics research. In particular, discovery and cataloging structural variants is incomplete, limiting potentially causative alleles phenotypic variation across individuals. Here, we utilized long-read sequencing resolve genome-wide (SVs, ≥ 50 bp) 20 genetically distinct mice. We report 413,758 site-specific SVs...
Abstract Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 in 41 human genomes. Approximately 85% of <2 kbp form by twin-priming during L1-retrotransposition; 80% the larger are balanced and affect twice as many base pairs CNVs. Balanced show excess common variants, 72% flanked segmental duplications (SDs) or mobile elements. Since this suggests recurrence due to non-allelic...