A5063580439- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- HIV/AIDS Research and Interventions
- Molecular Biology Techniques and Applications
- Cutaneous Melanoma Detection and Management
- Melanoma and MAPK Pathways
- Bladder and Urothelial Cancer Treatments
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- vaccines and immunoinformatics approaches
- Genetics, Aging, and Longevity in Model Organisms
- Urinary Tract Infections Management
- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- Reproductive tract infections research
- Genetic Associations and Epidemiology
- Pelvic floor disorders treatments
- Acute Myeloid Leukemia Research
Wellcome Sanger Institute
2015-2024
University of Washington
2004-2021
University of California System
2020
Science for Life Laboratory
2018
KTH Royal Institute of Technology
2018
Cancer Genetics (United States)
2018
Seattle University
2009-2012
BC Cancer Agency
2003-2009
University of Missouri
2003
University of Calgary
2003
Widespread adoption of massively parallel deoxyribonucleic acid (DNA) sequencing instruments has prompted the recent development de novo short read assembly algorithms. A common shortcoming available tools is their inability to efficiently assemble vast amounts data generated from large-scale projects, such as individual human genomes catalog natural genetic variation. To address this limitation, we developed ABySS ( ssembly By S hort equences), a parallelized sequence assembler. As...
We report genome sequences of 17 inbred strains laboratory mice and identify almost ten times more variants than previously known. use these genomes to explore the phylogenetic history mouse examine functional consequences allele-specific variation on transcript abundance, revealing that at least 12% transcripts show a significant tissue-specific expression bias. By identifying candidate 718 quantitative trait loci we molecular nature their position relative genes vary according effect size...
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high 80×) nearly 10,000 individuals population-based disease collections. In extensively phenotyped cohorts characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel identify alleles associated with levels triglycerides (APOB), adiponectin (ADIPOQ) low-density...
The mouse inbred line C57BL/6J is widely used in genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using C57BL/6N strain to generate null alleles for all genes. Hence both strains now studies. Here we perform a comprehensive genomic phenotypic analysis of two identify differences that may influence their underlying mechanisms.We undertake sequence comparisons...
Using DNA sequences 5′ to open reading frames, we have constructed green fluorescent protein (GFP) fusions and generated spatial temporal tissue expression profiles for 1,886 specific genes in the nematode Caenorhabditis elegans. This effort encompasses about 10% of all identified this organism. GFP-expressing wild-type animals were analyzed at each stage development from embryo adult. We regions regulating developmental stages 38 different cell types Among regulatory are that regulate...
Abstract Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity comprehensive mutation data on this rare tumor type. To better understand genomic landscape melanoma, here we describe whole genome sequencing analysis 67 tumors validation driver gene mutations by exome 45 tumors. Tumors have a low point burden high numbers structural variants, including recurrent rearrangements targeting TERT, CDK4 MDM2 . Significantly mutated genes are NRAS , BRAF...
We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. identify characterize 2,567 regions on the current reference exhibiting greatest sequence diversity. These are enriched genes involved in pathogen defence immunity exhibit enrichment of transposable elements signatures recent retrotransposition events. Combinations alleles unique to an individual strain commonly observed at these loci,...
Abstract Summary: A significant proportion of eukaryote genomes consist transposable element (TE)-derived sequence. These elements are known to have the capacity modulate gene function and genome evolution. We developed RetroSeq for detecting non-reference TE insertions from Illumina paired-end whole-genome sequencing data. evaluate on a human trio 1000 Genomes Project, showing that it produces highly accurate calls. Availabilty: is open-source available https://github.com/tk2/RetroSeq....
Abstract Background Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription translation. Our current knowledge TEs in laboratory mouse strains is limited primarily to those present C57BL/6J reference genome, with most being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long (LINEs) endogenous retrovirus (ERV) superfamily. Despite their high prevalence,...
Abstract We present a pipeline, SVMerge, to detect structural variants by integrating calls from several existing variant callers, which are then validated and the breakpoints refined using local de novo assembly. SVMerge is modular extensible, allowing new callers be incorporated as they become available. applied analysis of HapMap trio, demonstrating enhanced detection, breakpoint refinement, lower false discovery rate. can downloaded http://svmerge.sourceforge.net .
Abstract Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform cross-species analysis by sequencing tumor-germline pairs from 46 primary muscosal, 65 canine oral 28 equine cases mucosal sites. Analysis these data reveals recurrently mutated driver genes shared between species such as NRAS , FAT4, PTPRJ, TP53 PTEN pathogenic germline alleles BRCA1, BRCA2 . We identify UV mutation signature in small number samples, including the lip nasal mucosa. A...
The Mouse Genomes Project is an ongoing collaborative effort to sequence the genomes of common laboratory mouse strains. In 2011, initial analysis variation across 17 strains found 56.7 M unique single nucleotide polymorphisms (SNPs) and 8.8 indels. We carry out deep sequencing 13 additional inbred (BUB/BnJ, C57BL/10J, C57BR/cdJ, C58/J, DBA/1J, I/LnJ, KK/HiJ, MOLF/EiJ, NZB/B1NJ, NZW/LacJ, RF/J, SEA/GnJ ST/bJ), cataloguing molecular within These include important models for immune response,...
ABSTRACT Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of genetic changes T-cell immunity in one subject at ≤17 points his 3 years infecting partner near the transmission. Autologous peptides covering amino acid sites inferred be under positive selection were...
Abstract Background Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these include exiting mitosis and entering meiosis, progressing the various meiotic prophase, adopting either male (sperm) or female (oocyte) fate, completing meiosis. Additionally, many factors needed drive embryogenesis are synthesized in line. To increase our understanding genes that might be necessary for formation function line,...
A crucial step in the development of muscle cells all metazoan animals is assembly and anchorage sarcomere, essential repeat unit responsible for contraction. In Caenorhabditis elegans, many critical proteins involved this process have been uncovered through mutational screens focusing on uncoordinated movement embryonic arrest phenotypes. We propose that additional sarcomeric exist which there a less severe, or entirely different, mutant phenotype produced their absence. used Serial...
HIV-1 transmission and viral evolution in the first year of infection were studied 11 individuals representing four transmitter-recipient pairs three independent seroconverters. Nine these enrolled during acute infection; all men who have sex with (MSM) infected subtype B. A total 475 nearly full-length genome sequences generated, on average 10 genomes per specimen at 2 to 12 visits over infection. Single founding variants homogeneous populations detected eight nine Restriction a single...
Background Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants infectiousness and evaluate candidate interventions to reduce transmission. Although sequencing is frequently used substantiate linkage between newly infected individuals their sexual partners epidemiologic forensic studies, viral seldom applied prevention trials. The Partners Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized...
The FVB/NJ mouse strain has its origins in a colony of outbred Swiss mice established 1935 at the National Institutes Health. Mice derived from this source were selectively bred for sensitivity to histamine diphosphate and B Friend leukemia virus. This led establishment FVB/N inbred strain, which was subsequently imported Jackson Laboratory designated FVB/NJ. several distinct characteristics, such as large pronuclear morphology, vigorous reproductive performance, consistently litters that...