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65-474: The Dogo Argentino (plural Dogos Argentinos ) is an Argentine breed of large dog of mastiff type. It was bred in the early twentieth century in Córdoba in central Argentina, primarily for hunting large game such as peccaries , wild boar , and pumas . The foundation stock included the now extinct Córdoba fighting dog , a fighting dog of bulldog type , a Bull Terrier and a Mastín del Pirineo . In

130-451: A eukaryotic organelle , the human mitochondrion (16,568 bp, about 16.6 kb [kilobase]), was reported in 1981, and the first chloroplast genomes followed in 1986. In 1992, the first eukaryotic chromosome , chromosome III of brewer's yeast Saccharomyces cerevisiae (315 kb) was sequenced. The first free-living organism to be sequenced was that of Haemophilus influenzae (1.8 Mb [megabase]) in 1995. The following year

195-427: A polyacrylamide gel (called polyacrylamide gel electrophoresis) and visualised using autoradiography. The procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still very laborious. Nevertheless, in 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded bacteriophage φX174 , completing the first fully sequenced DNA-based genome. The refinement of

260-479: A 3'- OH group required for the formation of a phosphodiester bond between two nucleotides, causing DNA polymerase to cease extension of DNA when a ddNTP is incorporated. The ddNTPs may be radioactively or fluorescently labelled for detection in DNA sequencers . Typically, these machines can sequence up to 96 DNA samples in a single batch (run) in up to 48 runs a day. The high demand for low-cost sequencing has driven

325-642: A Preventive Genomics Clinic in August 2019, with Massachusetts General Hospital following a month later. The All of Us research program aims to collect genome sequence data from 1 million participants to become a critical component of the precision medicine research platform and the UK Biobank initiative has studied more than 500.000 individuals with deep genomic and phenotypic data. The growth of genomic knowledge has enabled increasingly sophisticated applications of synthetic biology . In 2010 researchers at

390-517: A base is incorporated. A microwell containing template DNA is flooded with a single nucleotide , if the nucleotide is complementary to the template strand it will be incorporated and a hydrogen ion will be released. This release triggers an ISFET ion sensor. If a homopolymer is present in the template sequence multiple nucleotides will be incorporated in a single flood cycle, and the detected electrical signal will be proportionally higher. Sequence assembly refers to aligning and merging fragments of

455-467: A combination of experimental and modeling approaches . The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein. With full-genome sequences available, structure prediction can be done more quickly through a combination of experimental and modeling approaches, especially because

520-471: A consortium of researchers from laboratories across North America , Europe , and Japan announced the completion of the first complete genome sequence of a eukaryote, S. cerevisiae (12.1 Mb), and since then genomes have continued being sequenced at an exponentially growing pace. As of October 2011 , the complete sequences are available for: 2,719 viruses , 1,115 archaea and bacteria , and 36 eukaryotes , of which about half are fungi . Most of

585-451: A field of study in biology ending in -omics , such as genomics, proteomics or metabolomics . The related suffix -ome is used to address the objects of study of such fields, such as the genome , proteome , or metabolome ( lipidome ) respectively. The suffix -ome as used in molecular biology refers to a totality of some sort; similarly omics has come to refer generally to the study of large, comprehensive biological data sets. While

650-501: A global level has been made possible only recently through the adaptation of genomic high-throughput assays. Metagenomics is the study of metagenomes , genetic material recovered directly from environmental samples. The broad field may also be referred to as environmental genomics, ecogenomics or community genomics. While traditional microbiology and microbial genome sequencing rely upon cultivated clonal cultures , early environmental gene sequencing cloned specific genes (often

715-408: A high error rate at approximately 1 percent. Typically the short fragments, called reads, result from shotgun sequencing genomic DNA, or gene transcripts ( ESTs ). Assembly can be broadly categorized into two approaches: de novo assembly, for genomes which are not similar to any sequenced in the past, and comparative assembly, which uses the existing sequence of a closely related organism as

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780-505: A key role in the development of DNA sequencing techniques that enabled the establishment of comprehensive genome sequencing projects. In 1975, he and Alan Coulson published a sequencing procedure using DNA polymerase with radiolabelled nucleotides that he called the Plus and Minus technique . This involved two closely related methods that generated short oligonucleotides with defined 3' termini. These could be fractionated by electrophoresis on

845-427: A much longer DNA sequence in order to reconstruct the original sequence. This is needed as current DNA sequencing technology cannot read whole genomes as a continuous sequence, but rather reads small pieces of between 20 and 1000 bases, depending on the technology used. Third generation sequencing technologies such as PacBio or Oxford Nanopore routinely generate sequencing reads 10-100 kb in length; however, they have

910-475: A protein of known structure or based on chemical and physical principles for a protein with no homology to any known structure. As opposed to traditional structural biology , the determination of a protein structure through a structural genomics effort often (but not always) comes before anything is known regarding the protein function. This raises new challenges in structural bioinformatics , i.e. determining protein function from its 3D structure. Epigenomics

975-515: A range of software tools in their automated genome annotation pipeline. Structural annotation consists of the identification of genomic elements, primarily ORFs and their localisation, or gene structure. Functional annotation consists of attaching biological information to genomic elements. The need for reproducibility and efficient management of the large amount of data associated with genome projects mean that computational pipelines have important applications in genomics. Functional genomics

1040-432: A reference during assembly. Relative to comparative assembly, de novo assembly is computationally difficult ( NP-hard ), making it less favourable for short-read NGS technologies. Within the de novo assembly paradigm there are two primary strategies for assembly, Eulerian path strategies, and overlap-layout-consensus (OLC) strategies. OLC strategies ultimately try to create a Hamiltonian path through an overlap graph which

1105-403: A spotted fighting dog of bulldog type . He selected and inter-bred their offspring, selecting for white coat colour and rejecting any animal that was retrognathous (undershot). In the eighth generation he introduced a Pyrenean mastiff bitch; by the twelfth generation his dogs were breeding true. They became well known for their success in the ring. Nores Martinez later introduced crosses with

1170-434: A substantial amount of microbial DNA consists of prophage sequences and prophage-like elements. A detailed database mining of these sequences offers insights into the role of prophages in shaping the bacterial genome: Overall, this method verified many known bacteriophage groups, making this a useful tool for predicting the relationships of prophages from bacterial genomes. At present there are 24 cyanobacteria for which

1235-628: A total genome sequence is available. 15 of these cyanobacteria come from the marine environment. These are six Prochlorococcus strains, seven marine Synechococcus strains, Trichodesmium erythraeum IMS101 and Crocosphaera watsonii WH8501 . Several studies have demonstrated how these sequences could be used very successfully to infer important ecological and physiological characteristics of marine cyanobacteria. However, there are many more genome projects currently in progress, amongst those there are further Prochlorococcus and marine Synechococcus isolates, Acaryochloris and Prochloron ,

1300-539: A variety of other dogs including the Irish Wolfhound , Boxer , Great Dane , Bull Terrier , Dogue de Bordeaux , and Spanish Mastiff . In 1947 he presented his breed to the Club de Cazadores ('hunter's club') of Buenos Aires ; in 1948 a breed standard was published in the magazine Diana . Antonio Nores Martinez was murdered in 1956; however Augustin, now an international ambassador , would continue to promote

1365-461: A whole new science discipline. Following Rosalind Franklin 's confirmation of the helical structure of DNA, James D. Watson and Francis Crick 's publication of the structure of DNA in 1953 and Fred Sanger 's publication of the Amino acid sequence of insulin in 1955, nucleic acid sequencing became a major target of early molecular biologists . In 1964, Robert W. Holley and colleagues published

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1430-499: A year, to local molecular biology core facilities) which contain research laboratories with the costly instrumentation and technical support necessary. As sequencing technology continues to improve, however, a new generation of effective fast turnaround benchtop sequencers has come within reach of the average academic laboratory. On the whole, genome sequencing approaches fall into two broad categories, shotgun and high-throughput (or next-generation ) sequencing. Shotgun sequencing

1495-502: Is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects ) to describe gene (and protein ) functions and interactions. Functional genomics focuses on the dynamic aspects such as gene transcription , translation , and protein–protein interactions , as opposed to the static aspects of the genomic information such as DNA sequence or structures. Functional genomics attempts to answer questions about

1560-471: Is a sequencing method designed for analysis of DNA sequences longer than 1000 base pairs, up to and including entire chromosomes. It is named by analogy with the rapidly expanding, quasi-random firing pattern of a shotgun . Since gel electrophoresis sequencing can only be used for fairly short sequences (100 to 1000 base pairs), longer DNA sequences must be broken into random small segments which are then sequenced to obtain reads . Multiple overlapping reads for

1625-732: Is an NP-hard problem. Eulerian path strategies are computationally more tractable because they try to find a Eulerian path through a deBruijn graph. Finished genomes are defined as having a single contiguous sequence with no ambiguities representing each replicon . The DNA sequence assembly alone is of little value without additional analysis. Genome annotation is the process of attaching biological information to sequences , and consists of three main steps: Automatic annotation tools try to perform these steps in silico , as opposed to manual annotation (a.k.a. curation) which involves human expertise and potential experimental verification. Ideally, these approaches co-exist and complement each other in

1690-587: Is based on reversible dye-terminators and was developed in 1996 at the Geneva Biomedical Research Institute, by Pascal Mayer and Laurent Farinelli. In this method, DNA molecules and primers are first attached on a slide and amplified with polymerase so that local clonal colonies, initially coined "DNA colonies", are formed. To determine the sequence, four types of reversible terminator bases (RT-bases) are added and non-incorporated nucleotides are washed away. Unlike pyrosequencing,

1755-483: Is kept principally for hunting large game such as peccaries , wild boar , and pumas . It has a good nose, good speed, and good stamina; it may occasionally be trained for police or military work. Ownership of dogs of this breed is illegal or restricted in some countries, including Australia, Austria (Lower Austria, Vienna and Vorarlberg), the Cayman Islands , Hong Kong, New Zealand, Norway, Turkey, and

1820-486: Is over-sampled is referred to as coverage . For much of its history, the technology underlying shotgun sequencing was the classical chain-termination method or ' Sanger method ', which is based on the selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication . Recently, shotgun sequencing has been supplanted by high-throughput sequencing methods, especially for large-scale, automated genome analyses. However,

1885-679: Is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome . Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence (Russell 2010 p. 475). Two of the most characterized epigenetic modifications are DNA methylation and histone modification . Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis . The study of epigenetics on

1950-411: The 16S rRNA gene) to produce a profile of diversity in a natural sample. Such work revealed that the vast majority of microbial biodiversity had been missed by cultivation-based methods. Recent studies use "shotgun" Sanger sequencing or massively parallel pyrosequencing to get largely unbiased samples of all genes from all the members of the sampled communities. Because of its power to reveal

2015-633: The J. Craig Venter Institute announced the creation of a partially synthetic species of bacterium , Mycoplasma laboratorium , derived from the genome of Mycoplasma genitalium . Population genomics has developed as a popular field of research, where genomic sequencing methods are used to conduct large-scale comparisons of DNA sequences among populations - beyond the limits of genetic markers such as short-range PCR products or microsatellites traditionally used in population genetics . Population genomics studies genome -wide effects to improve our understanding of microevolution so that we may learn

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2080-482: The Plus and Minus method resulted in the chain-termination, or Sanger method (see below ), which formed the basis of the techniques of DNA sequencing, genome mapping, data storage, and bioinformatic analysis most widely used in the following quarter-century of research. In the same year Walter Gilbert and Allan Maxam of Harvard University independently developed the Maxam-Gilbert method (also known as

2145-560: The United Kingdom , France and Germany . It states: " Great Britain and France are the ground zero of dog fancying, with 57 registered breeds each. Germany is not far behind, with 47 breeds. These three countries alone represent more than 40% of all dog breeds recognized by the Fédération Cynologique Internationale ." Genomics The field also includes studies of intragenomic (within

2210-477: The chemical method ) of DNA sequencing, involving the preferential cleavage of DNA at known bases, a less efficient method. For their groundbreaking work in the sequencing of nucleic acids, Gilbert and Sanger shared half the 1980 Nobel Prize in chemistry with Paul Berg ( recombinant DNA ). The advent of these technologies resulted in a rapid intensification in the scope and speed of completion of genome sequencing projects . The first complete genome sequence of

2275-478: The eukaryotic cell , while the fruit fly Drosophila melanogaster has been a very important tool (notably in early pre-molecular genetics ). The worm Caenorhabditis elegans is an often used simple model for multicellular organisms . The zebrafish Brachydanio rerio is used for many developmental studies on the molecular level, and the plant Arabidopsis thaliana is a model organism for flowering plants. The Japanese pufferfish ( Takifugu rubripes ) and

2340-475: The human genome was completed by the Human Genome Project in early 2001, creating much fanfare. This project, completed in 2003, sequenced the entire genome for one specific person, and by 2007 this sequence was declared "finished" (less than one error in 20,000 bases and all chromosomes assembled). In the years since then, the genomes of many other individuals have been sequenced, partly under

2405-442: The phylogenetic history and demography of a population. Population genomic methods are used for many different fields including evolutionary biology , ecology , biogeography , conservation biology and fisheries management . Similarly, landscape genomics has developed from landscape genetics to use genomic methods to identify relationships between patterns of environmental and genetic variation. Conservationists can use

2470-401: The spotted green pufferfish ( Tetraodon nigroviridis ) are interesting because of their small and compact genomes, which contain very little noncoding DNA compared to most species. The mammals dog ( Canis familiaris ), brown rat ( Rattus norvegicus ), mouse ( Mus musculus ), and chimpanzee ( Pan troglodytes ) are all important model animals in medical research. A rough draft of

2535-551: The 1920s Antonio Nores Martinez, a young student of Córdoba in central Argentina, set out with his brother Augustin Nores Martinez to create a new breed of big game hunting dog , especially wild boar. He wanted it to have the fighting qualities of the Old Cordoba Fighting Dog , but with greater size and strength. He started with a Bull Terrier bitch with considerable fighting ability, which he bred to

2600-416: The DNA chains are extended one nucleotide at a time and image acquisition can be performed at a delayed moment, allowing for very large arrays of DNA colonies to be captured by sequential images taken from a single camera. Decoupling the enzymatic reaction and the image capture allows for optimal throughput and theoretically unlimited sequencing capacity; with an optimal configuration, the ultimate throughput of

2665-470: The Dogo during his travels. The Dogo was definitively accepted by the Fédération Cynologique Internationale in 1973. The Dogo Argentino is a large dog: weights for dogs are some 40–45 kg (90–100 lb), for bitches slightly less; heights at the withers are in the range 60–65 cm (24–26 in) for bitches and 60–68 cm (24–27 in) for dogs. The length of the body is slightly greater than

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2730-449: The N 2 -fixing filamentous cyanobacteria Nodularia spumigena , Lyngbya aestuarii and Lyngbya majuscula , as well as bacteriophages infecting marine cyanobaceria. Thus, the growing body of genome information can also be tapped in a more general way to address global problems by applying a comparative approach. Some new and exciting examples of progress in this field are the identification of genes for regulatory RNAs, insights into

2795-481: The Sanger method remains in wide use, primarily for smaller-scale projects and for obtaining especially long contiguous DNA sequence reads (>500 nucleotides). Chain-termination methods require a single-stranded DNA template, a DNA primer , a DNA polymerase , normal deoxynucleosidetriphosphates (dNTPs), and modified nucleotides (dideoxyNTPs) that terminate DNA strand elongation. These chain-terminating nucleotides lack

2860-537: The United Kingdom. List of dog breeds This list of dog breeds includes both extant and extinct dog breeds , varieties and types . A research article on dog genomics published in Science/AAAS defines modern dog breeds as "a recent invention defined by conformation to a physical ideal and purity of lineage". According to BigThink , over 40% of the world's dog breeds come from

2925-575: The auspices of the 1000 Genomes Project , which announced the sequencing of 1,092 genomes in October 2012. Completion of this project was made possible by the development of dramatically more efficient sequencing technologies and required the commitment of significant bioinformatics resources from a large international collaboration. The continued analysis of human genomic data has profound political and social repercussions for human societies. The English-language neologism omics informally refers to

2990-411: The availability of large numbers of sequenced genomes and previously solved protein structures allow scientists to model protein structure on the structures of previously solved homologs. Structural genomics involves taking a large number of approaches to structure determination, including experimental methods using genomic sequences or modeling-based approaches based on sequence or structural homology to

3055-448: The development of high-throughput sequencing technologies that parallelize the sequencing process, producing thousands or millions of sequences at once. High-throughput sequencing is intended to lower the cost of DNA sequencing beyond what is possible with standard dye-terminator methods. In ultra-high-throughput sequencing, as many as 500,000 sequencing-by-synthesis operations may be run in parallel. The Illumina dye sequencing method

3120-623: The evolutionary origin of photosynthesis , or estimation of the contribution of horizontal gene transfer to the genomes that have been analyzed. Genomics has provided applications in many fields, including medicine , biotechnology , anthropology and other social sciences . Next-generation genomic technologies allow clinicians and biomedical researchers to drastically increase the amount of genomic data collected on large study populations. When combined with new informatics approaches that integrate many kinds of data with genomic data in disease research, this allows researchers to better understand

3185-557: The first nucleic acid sequence ever determined, the ribonucleotide sequence of alanine transfer RNA . Extending this work, Marshall Nirenberg and Philip Leder revealed the triplet nature of the genetic code and were able to determine the sequences of 54 out of 64 codons in their experiments. In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent ( Ghent , Belgium ) were

3250-465: The first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein. Fiers' group expanded on their MS2 coat protein work, determining the complete nucleotide-sequence of bacteriophage MS2-RNA (whose genome encodes just four genes in 3569 base pairs [bp]) and Simian virus 40 in 1976 and 1978, respectively. In addition to his seminal work on the amino acid sequence of insulin, Frederick Sanger and his colleagues played

3315-430: The function of DNA at the levels of genes, RNA transcripts, and protein products. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional "gene-by-gene" approach. A major branch of genomics is still concerned with sequencing the genomes of various organisms, but the knowledge of full genomes has created

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3380-480: The genetic bases of drug response and disease. Early efforts to apply the genome to medicine included those by a Stanford team led by Euan Ashley who developed the first tools for the medical interpretation of a human genome. The Genomes2People research program at Brigham and Women’s Hospital , Broad Institute and Harvard Medical School was established in 2012 to conduct empirical research in translating genomics into health. Brigham and Women's Hospital opened

3445-490: The genome) phenomena such as epistasis (effect of one gene on another), pleiotropy (one gene affecting more than one trait), heterosis (hybrid vigour), and other interactions between loci and alleles within the genome. From the Greek ΓΕΝ gen , "gene" (gamma, epsilon, nu, epsilon) meaning "become, create, creation, birth", and subsequent variants: genealogy, genesis, genetics, genic, genomere, genotype, genus etc. While

3510-425: The growth in the use of the term has led some scientists ( Jonathan Eisen , among others ) to claim that it has been oversold, it reflects the change in orientation towards the quantitative analysis of complete or near-complete assortment of all the constituents of a system. In the study of symbioses , for example, researchers which were once limited to the study of a single gene product can now simultaneously compare

3575-506: The height at the withers, up to a maximum of one tenth more. The coat is short and always white. A single black or dark-coloured spot on the head is tolerated as long as it is no larger than one tenth of the size of the head. The muzzle is of about the same length as the skull. Like many other breeds, the Dogo has some genetic predisposition to congenital deafness ; it is also predisposed to laryngeal paralysis/polyneuropathy complex . The dogs usually live for some 10 to 12 years. The Dogo

3640-438: The information gathered by genomic sequencing in order to better evaluate genetic factors key to species conservation, such as the genetic diversity of a population or whether an individual is heterozygous for a recessive inherited genetic disorder. By using genomic data to evaluate the effects of evolutionary processes and to detect patterns in variation throughout a given population, conservationists can formulate plans to aid

3705-467: The instrument depends only on the A/D conversion rate of the camera. The camera takes images of the fluorescently labeled nucleotides, then the dye along with the terminal 3' blocker is chemically removed from the DNA, allowing the next cycle. An alternative approach, ion semiconductor sequencing, is based on standard DNA replication chemistry. This technology measures the release of a hydrogen ion each time

3770-469: The microorganisms whose genomes have been completely sequenced are problematic pathogens , such as Haemophilus influenzae , which has resulted in a pronounced bias in their phylogenetic distribution compared to the breadth of microbial diversity. Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast ( Saccharomyces cerevisiae ) has long been an important model organism for

3835-415: The possibility for the field of functional genomics , mainly concerned with patterns of gene expression during various conditions. The most important tools here are microarrays and bioinformatics . Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome . This genome-based approach allows for a high-throughput method of structure determination by

3900-433: The previously hidden diversity of microscopic life, metagenomics offers a powerful lens for viewing the microbial world that has the potential to revolutionize understanding of the entire living world. Bacteriophages have played and continue to play a key role in bacterial genetics and molecular biology . Historically, they were used to define gene structure and gene regulation. Also the first genome to be sequenced

3965-660: The same annotation pipeline (also see below ). Traditionally, the basic level of annotation is using BLAST for finding similarities, and then annotating genomes based on homologues. More recently, additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. Some databases use genome context information, similarity scores, experimental data, and integrations of other resources to provide genome annotations through their Subsystems approach. Other databases (e.g. Ensembl ) rely on both curated data sources as well as

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4030-405: The target DNA are obtained by performing several rounds of this fragmentation and sequencing. Computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence. Shotgun sequencing is a random sampling process, requiring over-sampling to ensure a given nucleotide is represented in the reconstructed sequence; the average number of reads by which a genome

4095-507: The total complement of several types of biological molecules. After an organism has been selected, genome projects involve three components: the sequencing of DNA, the assembly of that sequence to create a representation of the original chromosome, and the annotation and analysis of that representation. Historically, sequencing was done in sequencing centers , centralized facilities (ranging from large independent institutions such as Joint Genome Institute which sequence dozens of terabases

4160-656: The word genome (from the German Genom , attributed to Hans Winkler ) was in use in English as early as 1926, the term genomics was coined by Tom Roderick, a geneticist at the Jackson Laboratory ( Bar Harbor, Maine ), over beers with Jim Womack, Tom Shows and Stephen O’Brien at a meeting held in Maryland on the mapping of the human genome in 1986. First as the name for a new journal and then as

4225-507: Was a bacteriophage . However, bacteriophage research did not lead the genomics revolution, which is clearly dominated by bacterial genomics. Only very recently has the study of bacteriophage genomes become prominent, thereby enabling researchers to understand the mechanisms underlying phage evolution. Bacteriophage genome sequences can be obtained through direct sequencing of isolated bacteriophages, but can also be derived as part of microbial genomes. Analysis of bacterial genomes has shown that

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