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48-829: Initially built and still managed by Jim Kent , then a graduate student, and David Haussler , professor of Computer Science (now Biomolecular Engineering) at the University of California, Santa Cruz in 2000, the UCSC Genome Browser began as a resource for the distribution of the initial fruits of the Human Genome Project . Funded by the Howard Hughes Medical Institute and the National Human Genome Research Institute, NHGRI (one of

96-523: A Linux-based operating system to run the software. In contrast, Celera was using what was thought then to be one of the most powerful civilian supercomputers in the world. Kent's first assembly on the human genome was released on June 22. Celera finished its assembly three days later on June 25, and the dual results were announced at the White House on June 26. On July 7, 2000, the Santa Cruz data

144-484: A SNP allele that is common in one geographical or ethnic group may be much rarer in another. However, this pattern of variation is relatively rare; in a global sample of 67.3 million SNPs, the Human Genome Diversity Project "found no such private variants that are fixed in a given continent or major region. The highest frequencies are reached by a few tens of variants present at >70% (and

192-461: A camera-ready image for publication in academic journals. One unique and useful feature that distinguishes the UCSC Browser from other genome browsers is the continuously variable nature of the display. Sequence of any size can be displayed, from a single DNA base up to the entire chromosome (human chr1 = 245 million bases, Mb) with full annotation tracks. Researchers can display a single gene,

240-542: A common consensus. The rs### standard is that which has been adopted by dbSNP and uses the prefix "rs", for "reference SNP", followed by a unique and arbitrary number. SNPs are frequently referred to by their dbSNP rs number, as in the examples above. The Human Genome Variation Society (HGVS) uses a standard which conveys more information about the SNP. Examples are: SNPs can be easily assayed due to only containing two possible alleles and three possible genotypes involving

288-777: A few thousands at >50%) in Africa, the Americas, and Oceania. By contrast, the highest frequency variants private to Europe, East Asia, the Middle East, or Central and South Asia reach just 10 to 30%." Within a population, SNPs can be assigned a minor allele frequency —the lowest allele frequency at a locus that is observed in a particular population. This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. With this knowledge scientists have developed new methods in analyzing population structures in less studied species. By using pooling techniques

336-409: A good probability of a match. This can additionally be applied to increase the accuracy of facial reconstructions by providing information that may otherwise be unknown, and this information can be used to help identify suspects even without a STR DNA profile match. Some cons to using SNPs versus STRs is that SNPs yield less information than STRs, and therefore more SNPs are needed for analysis before

384-528: A powerful tool to map genomic regions or genes that are involved in disease pathogenesis. Recently, preliminary results reported SNPs as important components of the epigenetic program in organisms. Moreover, cosmopolitan studies in European and South Asiatic populations have revealed the influence of SNPs in the methylation of specific CpG sites. In addition, meQTL enrichment analysis using GWAS database, demonstrated that those associations are important toward

432-751: A profile of a suspect is able to be created. Additionally, SNPs heavily rely on the presence of a database for comparative analysis of samples. However, in instances with degraded or small volume samples, SNP techniques are an excellent alternative to STR methods. SNPs (as opposed to STRs) have an abundance of potential markers, can be fully automated, and a possible reduction of required fragment length to less than 100bp.[26] Pharmacogenetics focuses on identifying genetic variations including SNPs associated with differential responses to treatment. Many drug metabolizing enzymes, drug targets, or target pathways can be influenced by SNPs. The SNPs involved in drug metabolizing enzyme activities can change drug pharmacokinetics, while

480-522: A set of genome analysis tools, including a full-featured GUI interface for mining the information in the browser database, a FASTA format sequence alignment tool BLAT that is also useful for simply finding sequences in the massive sequence (human genome = 3.23 billion bases [Gb]) of any of the featured genomes. A liftOver tool uses whole-genome alignments to allow conversion of sequences from one assembly to another or between species. The Genome Graphs tool allows users to view all chromosomes at once and display

528-547: A single nucleotide at a specific position in the genome . Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold. For example, a G nucleotide present at a specific location in a reference genome may be replaced by an A in a minority of individuals. The two possible nucleotide variations of this SNP – G or A – are called alleles . SNPs can help explain differences in susceptibility to

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576-426: A single coordinate axis makes the browser a handy tool for the vertical integration of the data. To find a specific gene or genomic region, the user may type in the gene name, a DNA sequence, an accession number for an RNA, the name of a genomic cytological band (e.g., 20p13 for band 13 on the short arm of chr20) or a chromosomal position (chr17:38,450,000-38,531,000 for the region around the gene BRCA1 ). Presenting

624-485: A single exon, or an entire chromosome band, showing dozens or hundreds of genes and any combination of the many annotations. A convenient drag-and-zoom feature allows the user to choose any region in the genome image and expand it to occupy the full screen. Researchers may also use the browser to display their own data via the Custom Tracks tool. This feature allows users to upload a file of their own data and view

672-592: A wide range of diseases across a population. For example, a common SNP in the CFH gene is associated with increased risk of age-related macular degeneration. Differences in the severity of an illness or response to treatments may also be manifestations of genetic variations caused by SNPs. For example, two common SNPs in the APOE gene, rs429358 and rs7412, lead to three major APO-E alleles with different associated risks for development of Alzheimer's disease and age at onset of

720-426: Is a hypothesis driven approach. Since only a limited number of SNPs are tested, a relatively small sample size is sufficient to detect the association. Candidate gene association approach is also commonly used to confirm findings from GWAS in independent samples. Genome-wide SNP data can be used for homozygosity mapping. Homozygosity mapping is a method used to identify homozygous autosomal recessive loci, which can be

768-625: Is a possibility in combining the advantages of SNPs with micro satellite markers. However, there are information lost in the process such as linkage disequilibrium and zygosity information. Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens , chemicals , drugs , vaccines , and other agents. SNPs are also critical for personalized medicine . Examples include biomedical research, forensics, pharmacogenetics, and disease causation, as outlined below. One of main contributions of SNPs in clinical research

816-460: Is available, now including 108 species . High coverage is necessary to allow overlap to guide the construction of larger contiguous regions. Genomic sequences with less coverage are included in multiple-alignment tracks on some browsers, but the fragmented nature of these assemblies does not make them suitable for building full featured browsers. (more below on multiple-alignment tracks). The species hosted with full-featured genome browsers are shown in

864-523: Is genome-wide association study (GWAS). Genome-wide genetic data can be generated by multiple technologies, including SNP array and whole genome sequencing. GWAS has been commonly used in identifying SNPs associated with diseases or clinical phenotypes or traits. Since GWAS is a genome-wide assessment, a large sample site is required to obtain sufficient statistical power to detect all possible associations. Some SNPs have relatively small effect on diseases or clinical phenotypes or traits. To estimate study power,

912-679: Is not homogenous; SNPs occur in non-coding regions more frequently than in coding regions or, in general, where natural selection is acting and "fixing" the allele (eliminating other variants) of the SNP that constitutes the most favorable genetic adaptation. Other factors, like genetic recombination and mutation rate, can also determine SNP density. SNP density can be predicted by the presence of microsatellites : AT microsatellites in particular are potent predictors of SNP density, with long (AT)(n) repeat tracts tending to be found in regions of significantly reduced SNP density and low GC content . There are variations between human populations, so

960-468: The Autodesk Animator for PC compatibles , where the image compression improved to the point it could play off of hard disk, and one could paint using "inks" that performed algorithmic transformations such as smoothing, transparency, and tiled patterns. The Autodesk Animator was used to create artwork for a wide variety of video games. In 2000, he wrote a program, GigAssembler, that allowed

1008-769: The GenArk Portal , including 2,589 assemblies hosted by both UCSC Genome Browser database and Assembly Hubs. An example can be seen in the Vertebrate Genomes Project assembly hub. The large amount of data about biological systems that is accumulating in the literature makes it necessary to collect and digest information using the tools of bioinformatics . The UCSC Genome Browser presents a diverse collection of annotation datasets (known as "tracks" and presented graphically), including mRNA alignments, mappings of DNA repeat elements, gene predictions, gene-expression data, disease-association data (representing

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1056-559: The intergenic regions (regions between genes). SNPs within a coding sequence do not necessarily change the amino acid sequence of the protein that is produced, due to degeneracy of the genetic code . SNPs in the coding region are of two types: synonymous SNPs and nonsynonymous SNPs. Synonymous SNPs do not affect the protein sequence, while nonsynonymous SNPs change the amino acid sequence of protein. SNPs that are not in protein-coding regions may still affect gene splicing , transcription factor binding, messenger RNA degradation, or

1104-583: The Aegis Animator program for the Amiga home computer. This program combined polygon tweening in 3D with simple 2D cel-based animation. In 1985 he founded and ran a software company, Dancing Flame, which adapted the Aegis Animator to the Atari ST , and created Cyber Paint for that machine. Cyber Paint was a 2D animation program that brought together a wide variety of animation and paint functionality and

1152-502: The SNPs involved in drug target or its pathway can change drug pharmacodynamics. Therefore, SNPs are potential genetic markers that can be used to predict drug exposure or effectiveness of the treatment. Genome-wide pharmacogenetic study is called pharmacogenomics . Pharmacogenetics and pharmacogenomics are important in the development of precision medicine, especially for life-threatening diseases such as cancers. Only small amount of SNPs in

1200-468: The SNPs with relatively small effect on diseases. For common and complex diseases, such as type-2 diabetes, rheumatoid arthritis, and Alzheimer's disease, multiple genetic factors are involved in disease etiology. In addition, gene-gene interaction and gene-environment interaction also play an important role in disease initiation and progression. As there are for genes, bioinformatics databases exist for SNPs. The International SNP Map working group mapped

1248-535: The Saved Sessions tool. Below the displayed images of the UCSC Genome browser are eleven categories of additional tracks that can be selected and displayed alongside the original data. Researchers can select tracks which best represent their query to allow for more applicable data to be displayed depending on the type and depth of research being done. These categories are as follows: The UCSC site hosts

1296-481: The UCSC Browser is optimized for speed. By pre-aligning millions of RNA secuences from GenBank to each of the 244 genome assemblies (many of the 108 species have more than one assembly), the browser allows instant access to the alignments of any RNA to any of the hosted species. The juxtaposition of the many types of data allow researchers to display exactly the combination of data that will answer specific questions. A pdf/postscript output functionality allows export of

1344-577: The US National Institutes of Health ), the browser offered a graphical display of the first full-chromosome draft assembly of human genome sequence. Today the browser is used by geneticists, molecular biologists and physicians as well as students and teachers of evolution for access to genomic information. In the years since its inception, the UCSC Browser has expanded to accommodate genome sequences of all vertebrate species and selected invertebrates for which high-coverage genomic sequences

1392-410: The cost of the analysis is significantly lowered. These techniques are based on sequencing a population in a pooled sample instead of sequencing every individual within the population by itself. With new bioinformatics tools there is a possibility of investigating population structure, gene flow and gene migration by observing the allele frequencies within the entire population. With these protocols there

1440-558: The data in the context of the reference genome assembly. Users may also use the data hosted by UCSC, creating subsets of the data of their choosing with the Table Browser tool (such as only the SNPs that change the amino acid sequence of a protein) and display this specific subset of the data in the browser as a Custom Track. Any browser view created by a user, including those containing Custom Tracks, may be shared with other users via

1488-523: The data in the graphical format allows the browser to present link access to detailed information about any of the annotations. The gene details page of the UCSC Genes track provides a large number of links to more specific information about the gene at many other data resources, such as Online Mendelian Inheritance in Man ( OMIM ) and SwissProt . Designed for the presentation of complex and voluminous data,

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1536-405: The delta-compressed animation format developed for CAD-3D. The user could move freely between animation frames and paint arbitrarily, or utilize various animation tools for automatic tweening movement across frames. Cyber Paint was one of the first, if not the first, consumer program that enabled the user to paint across time in a compressed digital video format. Later he developed a similar program,

1584-581: The disease. Single nucleotide substitutions with an allele frequency of less than 1% are sometimes called single-nucleotide variants (SNVs) . "Variant" may also be used as a general term for any single nucleotide change in a DNA sequence, encompassing both common SNPs and rare mutations , whether germline or somatic . The term SNV has therefore been used to refer to point mutations found in cancer cells. DNA variants must also commonly be taken into consideration in molecular diagnostics applications such as designing PCR primers to detect viruses, in which

1632-483: The genetic model for disease needs to be considered, such as dominant, recessive, or additive effects. Due to genetic heterogeneity, GWAS analysis must be adjusted for race. Candidate gene association study is commonly used in genetic study before the invention of high throughput genotyping or sequencing technologies. Candidate gene association study is to investigate limited number of pre-specified SNPs for association with diseases or clinical phenotypes or traits. So this

1680-529: The human genome may have impact on human diseases. Large scale GWAS has been done for the most important human diseases, including heart diseases, metabolic diseases, autoimmune diseases, and neurodegenerative and psychiatric disorders. Most of the SNPs with relatively large effects on these diseases have been identified. These findings have significantly improved understanding of disease pathogenesis and molecular pathways, and facilitated development of better treatment. Further GWAS with larger samples size will reveal

1728-525: The human genome. He helps maintain and upgrade the browser, and has worked on comparative genomics , Parasol, a job control management software for the UCSC kilocluster, and the ENCODE Project. Single-nucleotide polymorphism In genetics and bioinformatics , a single-nucleotide polymorphism ( SNP / s n ɪ p / ; plural SNPs / s n ɪ p s / ) is a germline substitution of

1776-411: The prediction of biological traits.   SNPs have historically been used to match a forensic DNA sample to a suspect but has been made obsolete due to advancing STR -based DNA fingerprinting techniques. However, the development of next-generation-sequencing (NGS) technology may allow for more opportunities for the use of SNPs in phenotypic clues such as ethnicity, hair color, and eye color with

1824-516: The publicly funded Human Genome Project to assemble and publish the first human genome sequence. His efforts were motivated by the research needs of himself and his colleagues, but also out of concern that the data might be made proprietary via patents by Celera Genomics . In their close race with Celera, Kent and the UCSC Professor David Haussler quickly built a modest cluster of 50 commodity personal computers running

1872-465: The relationships of genes to diseases), and mappings of commercially available gene chips (e.g., Illumina and Agilent ). The basic paradigm of display is to show the genome sequence in the horizontal dimension, and show graphical representations of the locations of the mRNAs, gene predictions, etc. Blocks of color along the coordinate axis show the locations of the alignments of the various data types. The ability to show this large variety of data types on

1920-437: The results of genome-wide association studies (GWAS). The Gene Sorter displays genes grouped by parameters not linked to genome location, such as expression pattern in tissues. The UCSC Browser code base is open-source for non-commercial use, and is mirrored locally by many research groups, allowing private display of data in the context of the public data. The UCSC Browser is mirrored at several locations worldwide, as shown in

1968-480: The sense that the source code can be downloaded and read for free, and all of the software can be freely used for academic, nonprofit, and personal use, some of it requires a license , either from UCSC or from Kent Informatics Inc., for commercial use. After GigAssembler, Kent went on to write BLAT (BLAST-like alignment tool) and the UCSC Genome Browser to help analyze important genome data. Kent continues to work at UCSC primarily on web tools to help understand

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2016-580: The sequence flanking each SNP by alignment to the genomic sequence of large-insert clones in Genebank. These alignments were converted to chromosomal coordinates that is shown in Table 1. This list has greatly increased since, with, for instance, the Kaviar database now listing 162 million single nucleotide variants (SNVs). The nomenclature for SNPs include several variations for an individual SNP, while lacking

2064-455: The sequence of noncoding RNA. Gene expression affected by this type of SNP is referred to as an eSNP (expression SNP) and may be upstream or downstream from the gene. More than 600 million SNPs have been identified across the human genome in the world's population. A typical genome differs from the reference human genome at 4 to 5 million sites, most of which (more than 99.9%) consist of SNPs and short indels . The genomic distribution of SNPs

2112-424: The table. Apart from these 108 species and their assemblies, the UCSC Genome Browser also offers Assembly Hubs , web-accessible directories of genomic data that can be viewed on the browser and include assemblies that are not hosted natively on it. There, users can load and annotate unique assemblies for which UCSC does not provide an annotation database. A full list of species and their assemblies can be viewed in

2160-878: The table. The Browser code is also used in separate installations by the UCSC Malaria Genome Browser and the Archaea Browser. Jim Kent William James Kent (born February 10, 1960) is an American research scientist and computer programmer . He has been a contributor to genome database projects and the 2003 winner of the Benjamin Franklin Award . Kent was born in Hawaii and grew up in San Francisco, California , United States . Kent began his programming career in 1983 with Island Graphics Inc. where he wrote

2208-1089: The two alleles: homozygous A, homozygous B and heterozygous AB, leading to many possible techniques for analysis. Some include: DNA sequencing ; capillary electrophoresis ; mass spectrometry ; single-strand conformation polymorphism (SSCP); single base extension ; electrochemical analysis; denaturating HPLC and gel electrophoresis ; restriction fragment length polymorphism ; and hybridization analysis. An important group of SNPs are those that corresponds to missense mutations causing amino acid change on protein level. Point mutation of particular residue can have different effect on protein function (from no effect to complete disruption its function). Usually, change in amino acids with similar size and physico-chemical properties (e.g. substitution from leucine to valine) has mild effect, and opposite. Similarly, if SNP disrupts secondary structure elements (e.g. substitution to proline in alpha helix region) such mutation usually may affect whole protein structure and function. Using those simple and many other machine learning derived rules

2256-495: The viral RNA or DNA sample may contain SNVs. However, this nomenclature uses arbitrary distinctions (such as an allele frequency of 1%) and is not used consistently across all fields; the resulting disagreement has prompted calls for a more consistent framework for naming differences in DNA sequences between two samples. Single-nucleotide polymorphisms may fall within coding sequences of genes , non-coding regions of genes , or in

2304-537: Was made publicly available on the World Wide Web while the research paper describing this publicly funded genome was published in February 2001 special issue of Nature , in parallel with Celera's results in the journal Science . In 2002 Tim O'Reilly described Kent's work as "the most significant work of open source development in the past year". While all of Kent's genomics software is open source in

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