1.
Chromosome
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A chromosome is a DNA molecule with part or all of the genetic material of an organism. Prokaryotes usually have one single circular chromosome, whereas most eukaryotes are diploid, chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes, a nucleosome is a histone octamer with part of a longer DNA strand attached to and wrapped around it. Chromatin fiber, together with associated proteins is known as chromatin, chromatin is present in most cells, with a few exceptions, for example, red blood cells. Occurring only in the nucleus of cells, chromatin contains the vast majority of DNA, except for a small amount inherited maternally. Chromosomes are normally visible under a microscope only when the cell is undergoing the metaphase of cell division. Before this happens every chromosome is copied once, and the copy is joined to the original by a centromere resulting in an X-shaped structure, the original chromosome and the copy are now called sister chromatids. During metaphase, when a chromosome is in its most condensed state, in this highly condensed form chromosomes are easiest to distinguish and study. In prokaryotic cells, chromatin occurs free-floating in cytoplasm, as these cells lack organelles, the main information-carrying macromolecule is a single piece of coiled double-helix DNA, containing many genes, regulatory elements and other noncoding DNA. The DNA-bound macromolecules are proteins that serve to package the DNA, chromosomes vary widely between different organisms. Some species such as certain bacteria also contain plasmids or other extrachromosomal DNA and these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. Chromosomal recombination during meiosis and subsequent sexual reproduction plays a significant role in genetic diversity. In prokaryotes and viruses, the DNA is often densely packed and organized, in the case of archaea, by homologs to eukaryotic histones, small circular genomes called plasmids are often found in bacteria and also in mitochondria and chloroplasts, reflecting their bacterial origins. Some use the term chromosome in a sense, to refer to the individualized portions of chromatin in cells. However, others use the concept in a sense, to refer to the individualized portions of chromatin during cell division. The word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes, schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now so familiar to everyone as chromosomes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, in a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity. His two principles were the continuity of chromosomes and the individuality of chromosomes and it is the second of these principles that was so original
2.
Human
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Modern humans are the only extant members of Hominina tribe, a branch of the tribe Hominini belonging to the family of great apes. Several of these hominins used fire, occupied much of Eurasia and they began to exhibit evidence of behavioral modernity around 50,000 years ago. In several waves of migration, anatomically modern humans ventured out of Africa, the spread of humans and their large and increasing population has had a profound impact on large areas of the environment and millions of native species worldwide. Humans are uniquely adept at utilizing systems of communication for self-expression and the exchange of ideas. Humans create complex structures composed of many cooperating and competing groups, from families. Social interactions between humans have established a wide variety of values, social norms, and rituals. These human societies subsequently expanded in size, establishing various forms of government, religion, today the global human population is estimated by the United Nations to be near 7.5 billion. In common usage, the word generally refers to the only extant species of the genus Homo—anatomically and behaviorally modern Homo sapiens. In scientific terms, the meanings of hominid and hominin have changed during the recent decades with advances in the discovery, there is also a distinction between anatomically modern humans and Archaic Homo sapiens, the earliest fossil members of the species. The English adjective human is a Middle English loanword from Old French humain, ultimately from Latin hūmānus, the words use as a noun dates to the 16th century. The native English term man can refer to the species generally, the species binomial Homo sapiens was coined by Carl Linnaeus in his 18th century work Systema Naturae. The generic name Homo is a learned 18th century derivation from Latin homō man, the species-name sapiens means wise or sapient. Note that the Latin word homo refers to humans of either gender, the genus Homo evolved and diverged from other hominins in Africa, after the human clade split from the chimpanzee lineage of the hominids branch of the primates. The closest living relatives of humans are chimpanzees and gorillas, with the sequencing of both the human and chimpanzee genome, current estimates of similarity between human and chimpanzee DNA sequences range between 95% and 99%. The gibbons and orangutans were the first groups to split from the leading to the humans. The splitting date between human and chimpanzee lineages is placed around 4–8 million years ago during the late Miocene epoch, during this split, chromosome 2 was formed from two other chromosomes, leaving humans with only 23 pairs of chromosomes, compared to 24 for the other apes. There is little evidence for the divergence of the gorilla, chimpanzee. Each of these species has been argued to be an ancestor of later hominins
3.
Cell (biology)
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The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life that can replicate independently, the study of cells is called cell biology. Cells consist of cytoplasm enclosed within a membrane, which contains many such as proteins. Organisms can be classified as unicellular or multicellular, while the number of cells in plants and animals varies from species to species, humans contain more than 10 trillion cells. Most plant and animal cells are only under a microscope. The cell was discovered by Robert Hooke in 1665, who named the unit for its resemblance to cells inhabited by Christian monks in a monastery. Cells emerged on Earth at least 3.5 billion years ago, Cells are of two types, eukaryotic, which contain a nucleus, and prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular, prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling and being self-sustaining. They are simpler and smaller than eukaryotic cells, and lack membrane-bound organelles such as the nucleus, prokaryotes include two of the domains of life, bacteria and archaea. The DNA of a prokaryotic cell consists of a chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid, most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. Though most prokaryotes have both a cell membrane and a wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, the cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment, some eukaryotic cells also have a cell wall. Inside the cell is the region that contains the genome, ribosomes. The genetic material is found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular, linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid, plasmids encode additional genes, such as antibiotic resistance genes
4.
Pseudogene
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Pseudogenes are segments of DNA that are related to real genes. Pseudogenes have lost at least some functionality, relative to the complete gene, pseudogenes often result from the accumulation of multiple mutations within a gene whose product is not required for the survival of the organism. Although not fully functional, pseudogenes may be functional, similar to kinds of noncoding DNA. The pseudo in pseudogene implies a variation in relative to the parent coding gene. Despite being non-coding, many pseudogenes have important roles in normal physiology, although some pseudogenes do not have introns or promoters, others have some gene-like features such as promoters, CpG islands, and splice sites. They are different from normal due to either a lack of protein-coding ability resulting from a variety of disabling mutations. The term pseudogene was coined in 1977 by Jacq et al, because pseudogenes were initially thought of as the last stop for genomic material that could be removed from the genome, they were often labeled as junk DNA. Nonetheless, pseudogenes contain biological and evolutionary histories within their sequences, pseudogenes are usually characterized by a combination of homology to a known gene and loss of some functionality. That is, although every pseudogene has a DNA sequence that is similar to some functional gene, homology is implied by sequence identity between the DNA sequences of the pseudogene and parent gene. After aligning the two sequences, the percentage of identical base pairs is computed, a high sequence identity means that it is highly likely that these two sequences diverged from a common ancestral sequence, and highly unlikely that these two sequences have evolved independently. Nonfunctionality can manifest itself in many ways, normally, a gene must go through several steps to a fully functional protein, Transcription, pre-mRNA processing, translation, and protein folding are all required parts of this process. If any of these steps fails, then the sequence may be considered nonfunctional, pseudogenes for RNA genes are usually more difficult to discover as they do not need to be translated and thus do not have reading frames. Pseudogenes can complicate molecular genetic studies, for example, amplification of a gene by PCR may simultaneously amplify a pseudogene that shares similar sequences. This is known as PCR bias or amplification bias, similarly, pseudogenes are sometimes annotated as genes in genome sequences. Processed pseudogenes often pose a problem for gene prediction programs, often being misidentified as real genes or exons and it has been proposed that identification of processed pseudogenes can help improve the accuracy of gene prediction methods. Recently 140 human pseudogenes have been shown to be translated, however, the function, if any, of the protein products is unknown. There are four types of pseudogenes, all with distinct mechanisms of origin. The classifications of pseudogenes are as follows, Processed pseudogenes, in higher eukaryotes, particularly mammals, retrotransposition is a fairly common event that has had a huge impact on the composition of the genome
5.
BRCA2
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BRCA2 and BRCA2 are a human gene and its protein product, respectively. The official symbol and the name are maintained by the HGNC. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex, orthologs, styled Brca2 and Brca2, are common in other mammal species. BRCA2 is a tumor suppressor gene, found in all humans, its protein. BRCA2 and BRCA1 are normally expressed in the cells of breast and other tissue and they are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double strand breaks. If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, BRCA1 and BRCA2 have been described as breast cancer susceptibility genes and breast cancer susceptibility proteins. The BRCA2 gene is located on the arm of chromosome 13 at position 12.3. The human reference BRCA2 gene contains 27 exons, and the cDNA has 10,254 base pairs coding for a protein of 3418 amino acids, the gene was first cloned by scientists at Myriad Genetics, Endo Recherche, Inc. HSC Research & Development Limited Partnership, and the University of Pennsylvania, methods to diagnose the likelihood of a patient with mutations in BRCA1 and BRCA2 getting cancer were covered by patents owned or controlled by Myriad Genetics. Although the structures of the BRCA1 and BRCA2 genes are very different, the proteins made by both genes are essential for repairing damaged DNA. BRCA2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion a vital step of homologous recombination, the localization of RAD51 to the DNA double-strand break requires the formation of BRCA1-PALB2-BRCA2 complex. PALB2 can function synergistically with a BRCA2 chimera to further promote strand invasion, double strand breaks are also generated during repair of DNA cross links. By repairing DNA, these play a role in maintaining the stability of the human genome and prevent dangerous gene rearrangements that can lead to hematologic. Like BRCA1, BRCA2 probably regulates the activity of other genes, certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause a risk of cancer. BRCA2 mutations are usually insertions or deletions of a number of DNA base pairs in the gene. As a result of mutations, the protein product of the BRCA2 gene is abnormal. Researchers believe that the defective BRCA2 protein is unable to fix DNA damages that occur throughout the genome, people who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia
6.
Karyotype
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A karyotype is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is used for the complete set of chromosomes in a species or in an individual organism. Karyotypes describe the chromosome count of an organism and what these chromosomes look like under a light microscope, attention is paid to their length, the position of the centromeres, banding pattern, any differences between the sex chromosomes, and any other physical characteristics. The preparation and study of karyotypes is part of cytogenetics, the study of whole sets of chromosomes is sometimes known as karyology. The chromosomes are depicted in a format known as a karyogram or idiogram, in pairs, ordered by size. The basic number of chromosomes in the cells of an individual or a species is called the somatic number and is designated 2n. In the germ-line the chromosome number is n. p28 Thus, so, in normal diploid organisms, autosomal chromosomes are present in two copies. There may, or may not, be sex chromosomes, polyploid cells have multiple copies of chromosomes and haploid cells have single copies. The study of karyotypes is important for cell biology and genetics, Karyotypes can be used for many purposes, such as to study chromosomal aberrations, cellular function, taxonomic relationships, and to gather information about past evolutionary events. Chromosomes were first observed in plant cells by Carl Wilhelm von Nägeli in 1842 and their behavior in animal cells was described by Walther Flemming, the discoverer of mitosis, in 1882. The name was coined by another German anatomist, Heinrich von Waldeyer in 1888 and it is New Latin from Ancient Greek κάρυον karyon, kernel, seed, or nucleus, and τύπος typos, general form). The next stage took place after the development of genetics in the early 20th century, lev Delaunay seems to have been the first person to define the karyotype as the phenotypic appearance of the somatic chromosomes, in contrast to their genic contents. The subsequent history of the concept can be followed in the works of C. D. Darlington, investigation into the human karyotype took many years to settle the most basic question, how many chromosomes does a normal diploid human cell contain. In 1912, Hans von Winiwarter reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism. Painter in 1922 was not certain whether the diploid of humans was 46 or 48, at first favouring 46, but revised his opinion from 46 to 48, considering the techniques of the time, these results were remarkable. In textbooks, the number of human chromosomes remained at 48 for over thirty years, New techniques were needed to correct this error. The work took place in 1955, and was published in 1956, the karyotype of humans includes only 46 chromosomes. Rather interestingly, the apes have 48 chromosomes
7.
DNA
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Deoxyribonucleic acid is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids, alongside proteins, lipids and complex carbohydrates, most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are termed polynucleotides since they are composed of simpler units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases—cytosine, guanine, adenine, or thymine —a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information and this information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences, the two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases and it is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription, under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells DNA is organized into structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, eukaryotic organisms store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast prokaryotes store their DNA only in the cytoplasm, within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed, DNA was first isolated by Friedrich Miescher in 1869. DNA is used by researchers as a tool to explore physical laws and theories, such as the ergodic theorem. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro-, among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a polymer made from repeating units called nucleotides
8.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
9.
GenBank
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The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. This database is produced and maintained by the National Center for Biotechnology Information as part of the International Nucleotide Sequence Database Collaboration, the National Center for Biotechnology Information is a part of the National Institutes of Health in the United States. GenBank and its collaborators receive sequences produced in laboratories throughout the world more than 100,000 distinct organisms. GenBank continues to grow at a rate, doubling every 18 months. Release 194, produced in February 2013, contained over 150 billion nucleotide bases in more than 162 million sequences, GenBank is built by direct submissions from individual laboratories, as well as from bulk submissions from large-scale sequencing centers. Only original sequences can be submitted to GenBank, direct submissions are made to GenBank using BankIt, which is a Web-based form, or the stand-alone submission program, Sequin. Upon receipt of a submission, the GenBank staff examines the originality of the data and assigns an accession number to the sequence. The submissions are then released to the database, where the entries are retrievable by Entrez or downloadable by FTP. Bulk submissions of Expressed Sequence Tag, Sequence-tagged site, Genome Survey Sequence, the GenBank direct submissions group also processes complete microbial genome sequences. Funding was provided by the National Institutes of Health, the National Science Foundation, the Department of Energy, LANL collaborated on GenBank with the firm Bolt, Beranek, and Newman, and by the end of 1983 more than 2,000 sequences were stored in it. In the mid 1980s, the Intelligenetics bioinformatics company at Stanford University managed the GenBank project in collaboration with LANL, as one of the earliest bioinformatics community projects on the Internet, the GenBank project started BIOSCI/Bionet news groups for promoting open access communications among bioscientists. During 1989 to 1992, the GenBank project transitioned to the newly created National Center for Biotechnology Information, the GenBank release notes for release 162.0 state that from 1982 to the present, the number of bases in GenBank has doubled approximately every 18 months. As of 15 June 2016, GenBank release 214.0 has 194,463,572 loci,213,200,907,819 bases, from 194,463,572 reported sequences. The GenBank database includes data sets that are constructed mechanically from the main sequence data collection. On the other hand, while commercial databases potentially contain high-quality filtered sequence data, the results showed that analyses performed using GenBank combined with EzTaxon-e were more discriminative than using GenBank or other databases alone. GenBank Example sequence record, for hemoglobin beta BankIt Sequin — a stand-alone software tool developed by the NCBI for submitting and updating entries to the GenBank sequence database. EMBOSS — free, open source software for molecular biology GenBank, RefSeq, TPA and UniProt, Whats in a Name
10.
Non-coding RNA
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A non-coding RNA is an RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA, non-messenger RNA, or functional RNA, the DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. The number of ncRNAs encoded within the genome is unknown, however. But see Many of the newly identified ncRNAs have not been validated for their function and it is also likely that many ncRNAs are non functional, and are the product of spurious transcription. Nucleic acids were first discovered in 1868 by Friedrich Miescher and by 1939 RNA had been implicated in protein synthesis. Two decades later, Francis Crick predicted a functional RNA component which mediated translation, the first non-coding RNA to be characterised was an alanine tRNA found in bakers yeast, its structure was published in 1965. To produce a purified alanine tRNA sample, Robert W. Holley et al. used 140kg of commercial bakers yeast to give just 1g of purified tRNAAla for analysis, the 80 nucleotide tRNA was sequenced by first being digested with Pancreatic ribonuclease and then with takadiastase ribonuclease Tl. Chromatography and identification of the 5 and 3 ends then helped arrange the fragments to establish the RNA sequence, of the three structures originally proposed for this tRNA, the cloverleaf structure was independently proposed in several following publications. The cloverleaf secondary structure was finalised following X-ray crystallography analysis performed by two independent research groups in 1974, ribosomal RNA was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with snoRNAs, Xist, CRISPR, recent notable additions include riboswitches and miRNA, the discovery of the RNAi mechanism associated with the latter earned Craig C. Mello and Andrew Fire the 2006 Nobel Prize in Physiology or Medicine, noncoding RNAs belong to several groups and are involved in many cellular processes. These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few related species. Many of the conserved, essential and abundant ncRNAs are involved in translation, ribonucleoprotein particles called ribosomes are the factories where translation takes place in the cell. The ribosome consists of more than 60% ribosomal RNA, these are made up of 3 ncRNAs in prokaryotes and 4 ncRNAs in eukaryotes, ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, Transfer RNAs, form an adaptor molecule between mRNA and protein, the H/ACA box and C/D box snoRNAs are ncRNAs found in archaea and eukaryotes. RNase MRP is restricted to eukaryotes, both groups of ncRNA are involved in the maturation of rRNA. The snoRNAs guide covalent modifications of rRNA, tRNA and snRNAs, the ubiquitous ncRNA, RNase P, is an evolutionary relative of RNase MRP. RNase P matures tRNA sequences by generating mature 5-ends of tRNAs through cleaving the 5-leader elements of precursor-tRNAs, another ubiquitous RNP called SRP recognizes and transports specific nascent proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes
11.
Human genome
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The human genome is the complete set of nucleic acid sequence for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. Human genomes include both protein-coding DNA genes and noncoding DNA, haploid human genomes, which are contained in germ cells consist of three billion DNA base pairs, while diploid genomes have twice the DNA content. The Human Genome Project produced the first complete sequences of human genomes, with the first draft sequence. The human genome was the first of all vertebrates to be completely sequenced, as of 2012, thousands of human genomes have been completely sequenced, and many more have been mapped at lower levels of resolution. The resulting data are used worldwide in biomedical science, anthropology, forensics, there is a widely held expectation that genomic studies will lead to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including human evolution. Although the sequence of the genome has been completely determined by DNA sequencing. There are an estimated 19, 000-20,000 human protein-coding genes, in June 2016, scientists formally announced HGP-Write, a plan to synthesize the human genome. The total length of the genome is over 3 billion base pairs. The genome is organized into 22 paired chromosomes, plus the X chromosome and, in males only and these are all large linear DNA molecules contained within the cell nucleus. The genome also includes the mitochondrial DNA, a small circular molecule present in each mitochondrion. Basic information about these molecules and their content, based on a reference genome that does not represent the sequence of any specific individual, are provided in the following table. Chromosome lengths were estimated by multiplying the number of base pairs by 0.34 nanometers, variations are unique DNA sequence differences that have been identified in the individual human genome sequences analyzed by Ensembl as of December,2016. The number of identified variations is expected to increase as further personal genomes are sequenced and analyzed, in addition to the gene content shown in this table, a large number of non-expressed functional sequences have been identified throughout the human genome. Links open windows to the reference chromosome sequences in the EBI genome browser, small non-coding RNAs are RNAs of as many as 200 bases that do not have protein-coding potential. These include, microRNAs, or miRNAs, small nuclear RNAs, or snRNAs, long non-coding RNAs are RNA molecules longer than 200 bases that do not have protein-coding potential. Although the human genome has been sequenced for all practical purposes. A recent study noted more than 160 euchromatic gaps of which 50 gaps were closed, however, there are still numerous gaps in the heterochromatic parts of the genome which is much harder to sequence due to numerous repeats and other intractable sequence features. The content of the genome is commonly divided into coding and noncoding DNA sequences
12.
Wilson disease protein
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Wilson disease protein, also known as ATP7B protein, is a copper-transporting P-type ATPase which is encoded by the ATP7B gene. ATP7B protein locates in trans-Golgi network of liver and brain, balances the copper level in the body by excreting excess copper into bile and plasma. Genetic disorder of the ATP7B gene may cause Wilsons disease, a disease in which copper accumulates in tissues leading to neurological or psychiatric issues and this protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized, Wilson disease is caused by various mutations. One of the common mutations is single base pair mutation, H1069Q, ATP7B protein is a copper-transporting P-type ATPase, synthesized as a membrane protein of 165 KDa in human hepatoma cell line, and which is 57% homologous to menkes disease associated protein ATP7A. The copper binding motif also shows an affinity to other transition metal ions like zinc Zn, cadmium Cd, gold Au. As a P-type ATPases, ATP7B undergoes auto-phosphorylation of a key conserved aspartic acid residue in the DKTGT motif, the ATP binding to the protein initiates the reaction and copper binds to the transmembrane region. Then phosphorylation occurs at the acid residue in the DKTGT motif with Cu release. Then dephosphorylation of the acid residue recovers the protein to ready for the next transport. Most of ATP7B protein is located in the network of hepatocytes. Small amount of ATP7B is located in the brain, as a copper-transporting protein, one major function is delivering copper to copper dependent enzymes in Golgi apparatus. In the human body, liver plays an important role in copper regulation including removal of extra copper, ATP7B participates in the physiological pathway in the copper removal process in two ways, secreting copper into plasma and excreting copper into bile. ATP7B receives copper from cytosolic protein Antioxidant 1 copper chaperone and this protein targets ATP7B directly in liver in order to transport copper. ATOX1 transfers copper from cytosol to the binding domain of ATP7B which control the catalytic activity of ATP7B. Several mutations in ATOX1 can block the copper pathways and cause Wilson disease, subsequent transport is promoted through the reduction of intramolecular disulphide bonds by GLRX catalysis. Wilson disease happens when accumulation of copper inside the liver causes mitochondrial damage and cell destruction, then, the loss of excretion of copper in bile leads to an increasing concentration of copper level in urine and causes kidney problems. Therefore, symptoms of Wilson disease could be various including kidney disease, the major cause is the malfunction of ATP7B by single base pair mutations, deletions, frame-shifts, splice errors in ATP7B gene
