query: the dmd mutation is found where in the human genome

pos: Dystrophin Dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. The DMD gene, encoding the dystrophin protein, is one of the longest human genes known, covering 2.3 megabases (0.08% of the human genome) at locus Xp21. The primary transcript in muscle measures about 2,100 kilobases and

pos: Duchenne muscular dystrophy of age. Most men affected with DMD become essentially “paralyzed from the neck down” by the age of 21. Muscle wasting begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck, followed by loss of arm muscles and respiratory muscles. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Cardiomyopathy particularly (dilated cardiomyopathy) is common, but the development of congestive heart failure or arrhythmia (irregular heartbeat) is only occasional. DMD is caused by a mutation of the dystrophin gene at locus Xp21, located on the short arm of the X chromosome. Dystrophin is responsible for connecting

neg: Duchenne muscular dystrophy to correct a mutation that leads to Duchenne muscular dystrophy (DMD). Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in the dystrophin gene in DNA, allowing the body’s DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the “defect” in a gene rather than just transiently adding a “functional” one. Genome editing through the CRISPR/Cas9 system is not currently feasible in humans. However, it may be possible, through advancements in technology, to use this technique

neg: Duchenne muscular dystrophy her two X chromosomes has a DMD mutation, a 50% chance exists that a female child will inherit that mutation as one of her two X chromosomes, and be a carrier. If that carrier has a male child, there is a 50% chance that he will inherit the X chromosome with the mutation, and will have DMD. Prenatal tests can tell whether the unborn child has the most common mutations. Many mutations are responsible for DMD, and some have not been identified, so genetic testing only works when family members with DMD have an identified mutation. Prior to invasive testing,

neg: Whole genome sequencing a disruptive innovation to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their consumables cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500 per 1 million basepairs). Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. An even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical

neg: NUMT genome are less than 1 kb in size. Yet, extremely large fragments of organelle DNA are found in some the plant genomes. As the genome evolves and alters over time by mutation, the number of NUMT in the genome differs over the course of evolution. NUMT enters the nucleus and inserts in the nDNA at different stages of the time. Due to constant mutation and instability of NUMT, the resemblance of this genome stretch to the mtDNA varies widely across the kingdom Animalia and even within the certain genome. For instance, the latest number of NUMT recorded in the human

neg: Mutation rate number of cell divisions to generate gametes. Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10 per base per 20 year generation (depending on the method of estimation); these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10 per base per generation. Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10 per site per generation. The rate for other forms of mutation also differs greatly from point mutations. An individual microsatellite locus often has a mutation rate on the order

neg: Whole genome sequencing twins) 100-year-old centenarians. Only 8 somatic differences were found, though somatic variation occurring in less than 20% of blood cells would be undetected. In the specifically protein coding regions of the human genome, it is estimated that there are about 0.35 mutations that would change the protein sequence between parent/child generations (less than one mutated protein per generation). In cancer, mutation frequencies are much higher, due to genome instability. This frequency can further depend on patient age, exposure to DNA damaging agents (such as UV-irradiation or components of tobacco smoke) and the activity/inactivity of DNA repair mechanisms. Furthermore, mutation frequency

neg: Human genome lacking introns and encoding mRNA sequences of 781 nt and a 215 amino acid protein (648 nt open reading frame). Dystrophin (DMD) is the largest protein-coding gene in the human reference genome, spanning a total of 2.2 MB, while Titin (TTN) has the longest coding sequence (114,414 bp), the largest number of exons (363), and the longest single exon (17,106 bp). Over the whole genome, the median size of an exon is 122 bp (mean = 145 bp), the median number of exons is 7 (mean = 8.8), and the median coding sequence encodes 367 amino acids (mean = 447

neg: Human mitochondrial molecular clock in coding and non-coding regions of the genome also differs as mutations in the coding region are subject to purifying selection. For this reason, some studies avoid coding region or synonymous mutations when calibrating the molecular clock. only consider synonymous mutations, they have recalibrated the molecular clock of human mtDNA as 7990 years per synonymous mutation over the mitochondrial genome. The mutation rate has been observed to vary with time. Mutation rates within the human species are faster than those observed along the human-ape lineage. The mutation rate is also thought to be faster in recent times, since the beginning

neg: Duchenne muscular dystrophy of mutation of the exon or exons that are affected. DNA testing confirms the diagnosis in most cases. If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted using a biopsy needle. The key tests performed on the biopsy sample for DMD are immunocytochemistry and immunoblotting for dystrophin, and should be interpreted by an experienced neuromuscular pathologist. These tests provide information on the presence or absence of the protein. Absence of the protein is a positive test for DMD. Where dystrophin is present, the tests indicate the

neg: Mutation requires a tremendous scientific effort. Once the consensus sequence is known, the mutations in a genome can be pinpointed, described, and classified. The committee of the Human Genome Variation Society (HGVS) has developed the standard human sequence variant nomenclature, which should be used by researchers and DNA diagnostic centers to generate unambiguous mutation descriptions. In principle, this nomenclature can also be used to describe mutations in other organisms. The nomenclature specifies the type of mutation and base or amino acid changes. Mutation rates vary substantially across species, and the evolutionary forces that generally determine mutation are the subject of ongoing

neg: Non-coding DNA germ cells. Mutation within these retro-transcribed sequences can inactivate the viral genome. Over 8% of the human genome is made up of (mostly decayed) endogenous retrovirus sequences, as part of the over 42% fraction that is recognizably derived of retrotransposons, while another 3% can be identified to be the remains of s. Much of the remaining half of the genome that is currently without an explained origin is expected to have found its origin in transposable elements that were active so long ago (> 200 million years) that random mutations have rendered them unrecognizable. Genome size variation in at least

neg: Eteplirsen Eteplirsen Eteplirsen (brand name Exondys 51) is a medication to treat, but not a cure, some types of Duchenne muscular dystrophy (DMD), caused by a specific mutation. Eteplirsen only targets specific mutations and thus is only useful in just over 1% of cases. After a debate surrounding the efficacy of the drug, eteplirsen received accelerated approval from the US Food and Drug administration in late 2016. A year's worth of treatment is expected to cost approximately $300,000. Duchenne muscular dystrophy is caused when a mutation in the DMD gene changes the DMD RNA so that it no longer codes for

neg: Human mitochondrial molecular clock mutation rates. Since the emergence of the species homo sapiens about 200,000 years ago, human population have expanded from a few thousand individuals living in Africa to over 6.5 billion all over the world. However, the expansion has not been uniform, so the history of human populations may consist of both bottlenecks and expansions. The mutation rate across the mitochondrial genome is not uniformly distributed. Certain regions of the genome are known to mutate more rapidly than others. The Hypervariable regions are known to be highly polymorphic relative to other parts of the genome. The rate at which mutations accumulate

neg: Human parts of the genome that are not under natural selection and which therefore accumulate mutations at a fairly steady rate, it is possible to reconstruct a genetic tree incorporating the entire human species since the last shared ancestor. Each time a certain mutation (SNP) appears in an individual and is passed on to his or her descendants, a haplogroup is formed including all of the descendants of the individual who will also carry that mutation. By comparing mitochondrial DNA, which is inherited only from the mother, geneticists have concluded that the last female common ancestor whose genetic marker is found

neg: RNA-targeting small molecule drugs splice site (5’ss) in a sequence-selective manner that is discrete from constitutive recognition. Ataluren is in clinical trials for the treatment of Duchenne Muscular Dystrophy (DMD). It is believed that Ataluren acts by promoting insertion of near-cognate tRNAs at the site of the nonsense codon without affecting transcription, mRNA processing, mRNA stability, or protein stability to give nonsense suppression. This drug would be effective for ~10% of patients with DMD who have a single mutation in the DMD gene causing a stop codon to appear prematurely (nonsense mutation). Compared to the number of drug candidates that have successfully made it

neg: Richard Cotton (geneticist) Cotton". The establishment of Human Mutation lead Cotton and his colleagues globally to begin efforts to unify the field and make the collection of genetic variation information systematic, standardized and complete across all genes. In 1996, to further stimulate activity in this area, Cotton originally set up the Human Genome Organization Mutation Database Initiative. In 2001 this became the Human Genome Variation Society. Then in the early 2000s, closely following the widely acclaimed completion of the Human Genome Project, it became clear that a more active and more internationally focused effort was needed to enable the systematic collection, curation, interpretation

neg: Ccdc78 one protein has been found to interact with CCDC78. An analysis performed from IntAct showed an interaction between CCDC78 and dAK1_1 in Yersinia pestis. CCDC78 has no known paralogs in the human genome. However, it has several orthologs in other organisms. Orthologs can be found throughout the animal kingdom. CCDC78 is highly conserved in mammals. The coiled-coil domain is highly conserved throughout all orthologs, demonstrating the importance of these domains. A mutation in this gene has been shown to cause a unique congenital myopathy. This mutation is caused by alternative splicing - a 222 bp in-frame insertion. A group of

neg: NUMT are being associated with them. Although the insertion of NUMTs was previously considered functionless pseudogenes, recent human NUMTs are shown to be a potentially mutagenic process that could damage the functional integrity of the human genome. The accumulation of mutation in NUMT, post-insertional alteration, mutagenic mechanism of NUMT insertion, MMEJ and NHEJ, DSB, as well as the place in which insertion hot spot is located can cause mutation and dramatic alterations of the genome structure at the integration site, interfere with the function of the genome, and exert substantial effects on the expression of genetic information. Moreover, Integration of mtDNA

neg: Eteplirsen functional dystrophin protein, usually due to a mutation that alters the reading frame of the RNA downstream of the mutation. If an exon with an appropriate number of bases lies near the mutation, by removing that exon the downstream reading frame can be corrected and production of partially functional dystrophin can be restored. This is the general strategy used for designing exon-skipping oligos for DMD; as there are 79 exons in the longest splice form of the dystrophin transcript, many different oligos are needed to address the range of mutations present in the population of people with DMD. Eteplirsen is

neg: Human evolutionary genetics base to millions of bases. A companion paper examined segmental duplications in the two genomes, whose insertion and deletion into the genome account for much of the indel sequence. They found that a total of 2.7% of euchromatic sequence had been differentially duplicated in one or the other lineage. The sequence divergence has generally the following pattern: Human-Chimp < Human-Gorilla « Human-Orangutan, highlighting the close kinship between humans and the African apes. Alu elements diverge quickly due to their high frequency of CpG dinucleotides which mutate roughly 10 times more often than the average nucleotide in the genome. The mutation

neg: Postzygotic mutation is also present in all other cells associated with the organism. Postzygotic mutation A post- zygotic mutation is a change in an organism's genome that is acquired during its lifespan, instead of being inherited from its parent(s) through fusion of two haploid gametes. Mutations that occur after the zygote has formed can be caused by a variety of sources that fall under two classes: spontaneous mutations and induced mutations. How detrimental a mutation is to an organism is dependent on what the mutation is, where it occurred in the genome and when it occurred. Post- zygotic changes to a genome

neg: DNA mismatch repair addition to a very high mutation burden, MMR deficiencies result in an unusual distribution of somatic mutations across the human genome: this suggests that MMR preferentially protects the gene-rich, early-replicating euchromatic regions. In contrast, the gene-poor, late-replicating heterochromatic genome regions exhibit high mutation rates in many human tumors. The histone modification H3K36me3, an epigenetic mark of active chromatin, has the ability to recruit the MSH2-MSH6 (hMutSα) complex. Consistently, regions of the human genome with high levels of H3K36me3 accumulate less mutations due to MMR activity. Lack of MMR often occurs in coordination with loss of other DNA repair genes. For

neg: Postzygotic mutation Postzygotic mutation A post- zygotic mutation is a change in an organism's genome that is acquired during its lifespan, instead of being inherited from its parent(s) through fusion of two haploid gametes. Mutations that occur after the zygote has formed can be caused by a variety of sources that fall under two classes: spontaneous mutations and induced mutations. How detrimental a mutation is to an organism is dependent on what the mutation is, where it occurred in the genome and when it occurred. Post- zygotic changes to a genome can be caused by small mutations that affect a single base

neg: Genome evolution differences and similarities between various genomes. Genome sequencing has progressed over time to include more and more complex genomes including the eventual sequencing of the entire human genome in 2001. By comparing genomes of both close relatives and distant ancestors the stark differences and similarities between species began to emerge as well as the mechanisms by which genomes are able to evolve over time. Prokaryotic genomes have two main mechanisms of evolution: mutation and horizontal gene transfer. A third mechanism, sexual reproduction, prominent in eukaryotes, is not found in bacteria although prokaryotes can acquire novel genetic material through the process

neg: Nonsense mutation mutation, which is a point mutation where a single nucleotide is changed to cause substitution of a different amino acid. Some genetic disorders, such as thalassemia and DMD, result from point-nonsense mutations. DNA: 5' - ATG ACT CAC CGA GCG CGA AGC TGA - 3' Suppose that a point-nonsense mutation was introduced at the fourth triplet in the DNA sequence (CGA) causing the cytosine to be replaced with thymine, yielding TGA in the DNA sequence. Since TGA is transcribed-then-translated as UGA, the resulting transcript and protein product would be: The remaining codons of the mRNA are not translated into amino

neg: Ezutromid Ezutromid Ezutromid is an orally administered small molecule utrophin modulator currently involved in a Phase 2 clinical trial produced by Summit Therapeutics for the treatment of Duchenne muscular dystrophy (DMD). DMD is a fatal x-linked recessive disease affecting approximately 1 in 5000 males and is a designated orphan disease by the FDA and European Medicines Agency. Approximately 1/3 of the children obtain DMD as a result of spontaneous mutation in the dystrophin gene and have no family history of the disease. Dystrophin is a vital component of mature muscle function, and therefore DMD patients have multifarious forms of defunct or

neg: Replication slippage Replication slippage Replication slippage, otherwise known as slipped-strand mispairing, is a form of mutation that leads to either a trinucleotide or dinucleotide expansion or contraction during DNA replication. A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements. DNA polymerase, the main enzyme to catalyze the polymerization of free deoxyribonucleotides into a newly forming DNA strand, plays a significant role in the occurrence of this mutation. When DNA

neg: Malignant transformation a larger number of exome mutations that are "passengers" that confer no selective growth advantage. Cancers also generally have genome instability, that includes a high frequency of mutations in the noncoding DNA that makes up about 98% of the human genome. The average number of DNA sequence mutations in the entire genome of breast cancer tissue is about 20,000. In an average melanom (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. A second underlying commonality in cancers is altered epigenetic regulation of transcription. In cancers, loss of gene expression occurs

neg: DNA repair a number of cancers (see MMEJ for summary), and are also shown in cyan. Differential activity of DNA repair pathways across various regions of the human genome causes mutations to be very unevenly distributed within tumor genomes. In particular, the gene-rich, early-replicating regions of the human genome exhibit lower mutation frequencies than the gene-poor, late-replicating heterochromatin. One mechanism underlying this involves the histone modification H3K36me3, which can recruit mismatch repair proteins, thereby lowering mutation rates in H3K36me3-marked regions. Another important mechanism concerns nucleotide excision repair, which can be recruited by the transcription machinery, lowering somatic mutation rates in active genes

neg: Carcinoma the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood. Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke.

neg: Duchenne muscular dystrophy amount and molecular size of dystrophin, helping to distinguish DMD from milder dystrophinopathy phenotypes. Over the past several years, DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of DMD. DMD is carried by an X-linked recessive gene. Males have only one X chromosome, so one copy of the mutated gene will cause DMD. Fathers cannot pass X-linked traits on to their sons, so the mutation is transmitted by the mother. If the mother is a carrier, and therefore one of

neg: Splice site mutation research, they were able to discover splicing—the fact that pre-mRNA is processed into mRNA once introns were removed from the RNA segment. These two scientists discovered the existence of splice sites, thereby changing the face of genomics research. They also discovered that the splicing of the messenger RNA can occur in different ways, opening up the possibility for a mutation to occur. Today, many different types of technologies exist in which splice sites can be located and analyzed for more information. The Human Splicing Finder is an online database stemming from the Human Genome Project data. The genome database identifies

neg: Human evolution that mutation. By comparing mitochondrial DNA which is inherited only from the mother, geneticists have concluded that the last female common ancestor whose genetic marker is found in all modern humans, the so-called mitochondrial Eve, must have lived around 200,000 years ago. Human evolutionary genetics studies how one human genome differs from the other, the evolutionary past that gave rise to it, and its current effects. Differences between genomes have anthropological, medical and forensic implications and applications. Genetic data can provide important insight into human evolution. There is little fossil evidence for the divergence of the gorilla, chimpanzee and hominin

neg: Drisapersen will continue to look into DMD and the next generation oligonucleotides. Drisapersen Drisapersen (also known as Kyndrisa, PRO051 and GSK2402968) is an experimental drug that was under development by BioMarin, after acquisition of Prosensa, for the treatment of Duchenne muscular dystrophy. The drug is a 2'-O-methyl phosphorothioate oligonucleotide that alters the splicing of the dystrophin RNA transcript, eliminating exon 51 from the mature dystrophin mRNA. Duchenne muscular dystrophy (DMD) is caused when a mutation in the dystrophin gene changes the RNA so that it no longer codes for functional dystrophin protein. This usually happens due to a mutation that alters

neg: Drisapersen frameshift mutation. If an exon with an appropriate number of bases lies near the mutation, removing that exon can correct the downstream reading frame, restoring the production of partially functional dystrophin. This is the general strategy used in the design of exon-skipping oligonucleotides for DMD. As there are 79 exons in the longest splice form of the dystrophin transcript, many different oligonucleotides are needed to address the range of mutations present in the population of people with DMD. The compound has completed Phase III trials and did not meet its primary endpoint. In January 2016, the FDA rejected drisapersen (Kyndrisa)

neg: Viral decay acceleration the mutation frequency as little as 2-fold results in collapse of the viral population. These therapeutics, termed VDA agents, accelerate the accumulation of additional mutations in the viral genome, progressively debilitating the virus which causes decay and eventual extinction of the entire viral population. Viral decay acceleration Viral decay acceleration (VDA) is a therapeutic strategy which increases the mutation frequency of a virus toward an error catastrophe threshold. Viruses evolve at rates approximately one million times faster than the human genome. The high mutation rate increases diversity within the viral population and facilitates survival in the face of host immune

neg: Zebrafish widely used as model organism to study muscular dystrophies. For example the "sapje" ("sap") mutant is the zebrafish orthologue of human Duchenne muscular dystrophy (DMD). The Machuca-Tzili and co-workers applied zebrafish to determine the role of alternative splicing factor, MBNL, in myotonic dystrophy type 1 (DM1) pathogenesis. More recently, Todd et al. described a new zebrafish model designed to explore the impact of CUG repeat expression during early development in DM1 disease. Zebrafish is also an excellent animal model to study congenital muscular dystrophies including CMD Type 1 A (CMD 1A) caused by mutation in the human laminin α2 (LAMA2)

neg: Mutation rate of 10, though this can differ greatly with length. Some sequences of DNA may be more susceptible to mutation. For example, stretches of DNA in human sperm which lack methylation are more prone to mutation. In general, the mutation rate in unicellular eukaryotes (and bacteria) is roughly 0.003 mutations per genome per "cell" generation. However, some species, especially the ciliate of the genus "Paramecium" have an unusually low mutation rate. For instance, "Paramecium tetraurelia" has a base-substitution mutation rate of ~2 × 10 per site per cell division. This is the lowest mutation rate observed in nature so far, being

neg: Whole genome sequencing can vary between cancer types: in germline cells, mutation rates occur at approximately 0.023 mutations per megabase, but this number is much higher in breast cancer (1.18-1.66 somatic mutations per Mb), in lung cancer (17.7) or in melanomas (≈33). Since the haploid human genome consists of approximately 3,200 megabases, this translates into about 74 mutations (mostly in noncoding regions) in germline DNA per generation, but 3,776-5,312 somatic mutations per haploid genome in breast cancer, 56,640 in lung cancer and 105,600 in melanomas. The distribution of somatic mutations across the human genome is very uneven, such that the gene-rich, early-replicating regions

neg: Variant of uncertain significance gene. In 1977, in the third of a series of 3 research papers published in "The Journal of Biological Chemistry", this mutation was identified as a single base transversion of adenosine to uridine. In 2001, an initial draft of the human genome was published by the International Human Genome Sequencing Consortium. With the development of next-generation sequencing, the cost of sequencing has plummeted and the number of human genomes and exomes sequenced each year is increasing dramatically. , the cost of a quality whole genome sequence is $1,000 or less. If the ratio of approximately 20 DNA sequence variants per

neg: Human germline engineering human embryos with precise CRISPR–Cas9 targeting. 52% of human embryos were successfully edited to retain only the wild type normal copy of MYBPC3 gene, the rest of the embryos were mosaic, where some cells in the zygote contained the normal gene copy and some contained the mutation. In November 2018, researcher Jiankui He claimed that he had created the first human genetically edited babies, known by their pseudonyms, Lulu () and Nana ().{ Human genetic modification is the direct manipulation of the genome using molecular engineering. The two different types of gene modification is "somatic gene modification" and "germline genetic

neg: Long interspersed nuclear element for another protein named ORF1. LINE elements are relatively rare compared to LTR-retrotransposons in plants, fungi or insects, but are dominant in vertebrates and especially in mammals, where they represent around 20% of the genome. The LINE-1/L1-element is the only element that is still active in the human genome today. It is found in all mammals. Remnants of L2 and L3 elements are found in the human genome. It is estimated, that L2 and L3 elements were active ~200-300 million years ago. Unlike L1 elements, L2 and L3 elements lack flanking target site duplications. In the first human genome draft

neg: Exon skipping used to determine the precise nature and location of the DMD mutation in the dystrophin gene. It is known that these mutations cluster in areas known as the 'hot spot' regions — primarily in exons 45–53 and to a lesser extent exons 2–20. As the majority of DMD mutations occur in these 'hot spot' regions, a treatment which causes these exons to be skipped could be used to treat up to 50% of DMD patients. Exon skipping In molecular biology, exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections of

neg: Human genome others appear as re-arrangements of stretches of sequence. These variations include differences in the number of copies individuals have of a particular gene, deletions, translocations and inversions. Single-nucleotide polymorphisms (SNPs) do not occur homogeneously across the human genome. In fact, there is enormous diversity in SNP frequency between genes, reflecting different selective pressures on each gene as well as different mutation and recombination rates across the genome. However, studies on SNPs are biased towards coding regions, the data generated from them are unlikely to reflect the overall distribution of SNPs throughout the genome. Therefore, the SNP Consortium protocol was designed

neg: Cancer Genome Project of the project. The project works to combine knowledge of the human genome sequence with high throughput mutation detection techniques. The project operates within the scope of the International Cancer Genome Consortium, working with the other participating organizations and countries to build a database of genomic changes present in different types of cancer. The somatic mutation information gathered by the project can be located in the COSMIC database. The Wellcome Trust Sanger Institute's project currently has several internal partners that each focus on different types of cancer and mutagenesis utilizing different methods. Research goes beyond just sequencing to include therapeutic

neg: Frameshift mutation overlap with other databases. When a frameshift mutation is observed it is compared against the Human Genome Mutation Database (HGMD) to determine if the mutation has a damaging effect. This is done by looking at four features. First, the ratio between the affected and conserved DNA, second the location of the mutation relative to the transcript, third the ratio of conserved and affected amino acids and finally the distance of the indel to the end of the exon. Massively Parallel Sequencing is a newer method that can be used to detect mutations. Using this method, up to 17 gigabases can

neg: Cancer epigenetics with a high frequency of mutations. A high frequency of genomic mutations increases the likelihood of particular mutations occurring that activate oncogenes and inactivate tumor suppressor genes, leading to carcinogenesis. On the basis of whole genome sequencing, cancers are found to have thousands to hundreds of thousands of mutations in their whole genomes. (Also see Mutation frequencies in cancers.) By comparison, the mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. In the protein coding regions of the genome, there are only about 0.35 mutations between parent/child generations (less

neg: Mutation rate can be used to estimate how long ago two species diverged (see molecular clock). In fact, the mutation rate of an organism may change in response to environmental stress. For example, UV light damages DNA, which may result in error prone attempts by the cell to perform DNA repair. The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but estimates of the exact rate have varied by an order of magnitude or more. This means that a human genome accumulates around 64 new mutations per generation because each full generation involves a

neg: Human mitochondrial molecular clock used for dating genetic events. In practice the assumption of a single uniform rate is an oversimplification. Though a single mutation rate is often applied, it is often a composite or an average of several different mutation rates. Many factors influence observed mutation rates and these factors include the type of samples, the region of the genome studied and the time period covered. The rate at which mutations occur during reproduction, the germline mutation rate, is thought to be higher than all observed mutation rates, because not all mutations are successfully passed down to subsequent generations. MtDNA is only passed

neg: Cancer Genome Project Cancer Genome Project The Cancer Genome Project is part of the cancer, aging, and somatic mutation research based at the Wellcome Trust Sanger Institute in The United Kingdom. It aims to identify sequence variants/mutations critical in the development of human cancers. Like The Cancer Genome Atlas project within the United States, the Cancer Genome Project represents an effort in the War on Cancer to improve cancer diagnosis, treatment, and prevention through a better understanding of the molecular basis of the disease. The Cancer Genome Project was launched by Michael Stratton in 2000, and Peter Campbell is now the group leader

neg: Human evolutionary genetics and would thus have arisen after the development of rice cultivation roughly 10,000 years ago. Several phenotypical traits of characteristic of East Asians are due to a single mutation of the EDAR gene, dated to c. 35,000 years ago. , the Single Nucleotide Polymorphism Database (dbSNP), which lists SNP and other variants, listed a total of 324 million variants found in sequenced human genomes. Nucleotide diversity, the average proportion of nucleotides that differ between two individuals, is estimated at between 0.1% and 0.4% for contemporary humans (compared to 2% between humans and chimpanzees). This corresponds to genome differences at a

neg: Exon skipping the deletion. This allows for a shorter-than-normal dystrophin protein that maintains a degree of functionality. In Duchenne muscular dystrophy, the genetic mutation is out-of-frame. Out-of-frame mutations cause a premature stop in protein generation - the ribosome is unable to “read” the RNA past the point of initial error - leading to a severely shortened and completely non-functional dystrophin protein. The goal of exon skipping is to manipulate the splicing pattern so that an out-of-frame mutation becomes an in-frame mutation, thus changing a severe DMD mutation into a less harmful in-frame BMD mutation. Genetic testing, usually from blood samples, can be

neg: Human genome to identify SNPs with no bias towards coding regions and the Consortium's 100,000 SNPs generally reflect sequence diversity across the human chromosomes.The SNP Consortium aims to expand the number of SNPs identified across the genome to 300 000 by the end of the first quarter of 2001. Changes in non-coding sequence and synonymous changes in coding sequence are generally more common than non-synonymous changes, reflecting greater selective pressure reducing diversity at positions dictating amino acid identity. Transitional changes are more common than transversions, with CpG dinucleotides showing the highest mutation rate, presumably due to deamination. A personal genome sequence is

neg: Non-coding DNA sequence conservation. Noncoding DNA separates genes from each other with long gaps, so mutation in one gene or part of a chromosome, for example deletion or insertion, does not have a frameshift effect on the whole chromosome. When genome complexity is relatively high, like in the case of human genome, not only between different genes, but also inside many genes, there are gaps of introns to protect the entire coding segment and minimise the changes caused by mutation. Non-coding DNA may perhaps serve to decrease the probability of gene disruption during chromosomal crossover. Some noncoding DNA sequences determine the expression

neg: Genome instability genome instability since DNA damages can cause inaccurate translesion synthesis past the damages or errors in repair, leading to mutation. Another source of genome instability may be epigenetic or mutational reductions in expression of DNA repair genes. Because endogenous (metabolically-caused) DNA damage is very frequent, occurring on average more than 60,000 times a day in the genomes of human cells, any reduced DNA repair is likely an important source of genome instability. Usually, all cells in an individual in a given species (plant or animal) show a constant number of chromosomes, which constitute what is known as the karyotype defining

neg: Hypogammaglobulinemia or secondary immunodeficiency. Primary immunodeficiencies are caused by a mutation or series of mutations to the genome. For example, a study from 2012 found that a compound heterozygous deleterious mutation in the CD21 gene is associated with hypogammaglobulinemia. Genetic analysis revealed the patient was heterozygous for CD21, with the paternally inherited allele (also shared with one sister) having a disrupted splicing donor site at exon 6, while the maternally inherited allele had a mutation resulting in a premature stop codon in exon 13. Neither mutation was found in 100 healthy control subjects, showing the rarity of the mutations. Around 300

neg: Obsessive–compulsive disorder for 45–65% of the variability in OCD symptoms in children diagnosed with the disorder. A 2007 study found evidence supporting the possibility of a heritable risk for OCD. A mutation has been found in the human serotonin transporter gene, hSERT, in unrelated families with OCD. A systematic review found that while neither allele was associated with OCD overall, in caucasians the L allele was associated with OCD. Another meta analysis observed an increased risk in those with the homozygous S allele, but found the LS genotype to be inversely associated with OCD. A genome wide association study found OCD to

neg: DNA transposon in to the bacterium, where the resistance genes were transposed in to the chromosomal genome. Class II transposable elements make up about 3% of the human genome. Today, there are no active DNA Transposons in the human genome. Therefore, the elements found in the human genome are called "fossils". DNA transposon DNA transposons (also called Class II elements) are a group of transposable elements (TEs) that can move in the DNA of an organism via a single- or double-stranded DNA intermediate. DNA transposons have been found in both prokaryotic and eukaryotic organisms. They can make up a significant portion of

neg: Neoteny in humans significantly more defunct pseudogenes with functional homologs in the chimpanzee genome than vice versa. While the protein coding portion of the FOXP2 gene is identical to that in Neanderthals, there is one point mutation in the regulatory part thereof (modern humans having a T where Neanderthals and all nonhuman vertebrates have an A). The observation that the effect of that difference is that the modern human FOXP2 gene does not interact with RNA from other genes while all other vertebrate including Neanderthal varieties did agrees with the idea that modern human origins was marked by the elimination (not formation) of

neg: Mutation rate about 75× lower than in other eukaryotes with a similar genome size, and even 10× lower than in most prokaryotes. The low mutation rate in "Paramecium" has been explained by its transcriptionally silent germ-line nucleus, consistent with the hypothesis that replication fidelity is higher at lower gene expression levels. The highest per base pair per generation mutation rates are found in viruses, which can have either RNA or DNA genomes. DNA viruses have mutation rates between 10 to 10 mutations per base per generation, and RNA viruses have mutation rates between 10 to 10 per base per generation. The mutation

neg: Genome instability occur in the exome (protein coding region) of a cancer. However, a much larger number of mutations occur in the non-protein-coding regions of DNA. The average number of DNA sequence mutations in the entire genome of a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. The high frequency of mutations in the total genome within cancers suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. Mutation rates substantially increase (sometimes by 100-fold)

neg: Genome evolution the code. The "copy-and-paste" mechanism works by making a genetic copy or copies of a specific region of DNA and inserting these copies elsewhere in the code. The most common transposable element in the human genome is the Alu sequence, which is present in the genome over one million times. Spontaneous mutations often occur which can cause various changes in the genome. Mutations can either change the identity of one or more nucleotides, or result in the addition or deletion of one or more nucleotide bases. Such changes can lead to a frameshift mutation, causing the entire code to be

neg: Cancer genome sequencing the tumor genome and a matched normal tissue. By comparison, the original draft of the human genome had approximately 65-fold coverage. A major goal of cancer genome sequencing is to identify driver mutations: genetic changes which increase the mutation rate in the cell, leading to more rapid tumor evolution and metastasis. It is difficult to determine driver mutations from DNA sequence alone; but drivers tend to be the most commonly shared mutations amongst tumors, cluster around known oncogenes, and are tend to be non-silent. Passenger mutations, which are not important in the progression of the disease, are randomly distributed throughout

neg: Genome evolution functional gene can become a pseudogene including the deletion or insertion of one or multiple nucleotides. This can result in a shift of reading frame, causing the gene to no longer code for the expected protein, introduce a premature stop codon or a mutation in the promoter region. Often cited examples of pseudogenes within the human genome include the once functional olfactory gene families. Over time, many olfactory genes in the human genome became pseudogenes and were no longer able to produce functional proteins, explaining the poor sense of smell humans possess in comparison to their mammalian relatives. Exon shuffling

neg: Minisatellite sometimes are part of possible genes. Minisatellites also constitute the chromosomal telomeres, which protect the ends of a chromosome from deterioration or from fusion with neighbouring chromosomes. Minisatellites have been associated with chromosome fragile sites and are proximal to a number of recurrent translocation breakpoints. Some human minisatellites (~1%) have been demonstrated to be hypermutable, with an average mutation rate in the germline higher than 0.5% up to over 20%, making them the most unstable region in the human genome known to date. While other genomes (mouse, rat and pig) contain minisatellite-like sequences, none was found to be hypermutable. Since

neg: Advanced sleep phase disorder reporting the finding of FASPD, Ptáček's and Fu's groups published results of genetic sequencing analysis on a family with FASPD. They genetically mapped the FASPD locus to chromosome 2q where very little human genome sequence was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2). Sequencing of the hPer2 gene revealed a serine-to-glycine point mutation in the CKI binding domain of the hPER2 protein that resulted in hypophosphorylation of Per2 in vitro. In 2005, Fu's and Ptáček's labs reported discovery of a different mutation causing FASPD. This time, CKIδ

neg: Genome size and experienced extensive genome reduction as a result. This process seems to be dominated by genetic drift resulting from small population size, low recombination rates, and high mutation rates, as opposed to selection for smaller genomes. Some free-living marine bacterioplanktons also shows signs of genome reduction, which are hypothesized to be driven by natural selection. Obligate endosymbiotic species are characterized by a complete inability to survive external to their host environment. These species have become a considerable threat to human health, as they are often highly capable of evading human immune systems and manipulating the host environment to acquire nutrients.

neg: War on Cancer different types of cancer, in order to help researchers understand the genetic changes underlying cancer. New, targeted therapeutic approaches are expected to arise from the insights resulting from such studies. The Cancer Genome Project at the Wellcome Trust Sanger Institute aims to identify sequence variants/mutations critical in the development of human cancers. The Cancer Genome Project combines knowledge of the human genome sequence with high throughput mutation detection techniques. Advances in information technology supporting cancer research, such as the NCI's caBIG project, promise to improve data sharing among cancer researchers and accelerate "the discovery of new approaches for the detection,

neg: Genetic screen in which the regions of genetic polymorphisms are known, positional cloning involves identifying polymorphisms that flank the mutation. This process requires that DNA fragments from the closest known genetic marker are progressively cloned and sequenced, getting closer to the mutant allele with each new clone. This process produces a contig map of the locus and is known as chromosome walking. With the completion of genome sequencing projects such as the Human Genome Project, modern positional cloning can use ready-made contigs from the genome sequence databases directly. For each new DNA clone a polymorphism is identified and tested in the mapping

neg: Suppressor mutation deleted triplet does not disturb the reading frame and the genetic code is in fact a triplet. Intergenic (also known as extragenic) suppression relieves the effects of a mutation in one gene by a mutation somewhere else within the genome. The second mutation is not on the same gene as the original mutation. Intergenic suppression is useful for identifying and studying interactions between molecules, such as proteins. For example, a mutation which disrupts the complementary interaction between protein molecules may be compensated for by a second mutation elsewhere in the genome that restores or provides a suitable alternative interaction between

neg: Eteplirsen The most common treatment for DMD is glucocorticoid use, which do not sufficiently ameliorate symptoms or address the underlying genetic mutation and lack of functional dystrophin. Part of the document included the following information pertaining to the pharmacokinetic properties of eteplirsen: Eteplirsen is a morpholino phosphorodiamidate antisense oligomer. CTCCAACATCAAGGAAGATGGCATTTCTAG (sequence source: US FDA ETEPLIRSEN BRIEFING DOCUMENT NDA 206488), 30-mer, 20% G, 43% CG, Predicted Tm: 88.9 °C at 10 µM oligo. Oligo complement CTAGAAATGCCATCTTCCTTGATGTTGGAG DMD-001 Exon 51, ENST00000357033.8 in Ensembl.org, RNA target site marked. Given that the target site is within an exon, this is likely blocking binding of an

neg: DNA nanoball sequencing mutation rate. The Institute for Systems Biology has used this technology to sequence 615 complete human genome samples as part of a survey studying neurodegenerative diseases, and the National Cancer Institute is using DNA nanoball sequencing to sequence 50 tumours and matched normal tissues from pediatric cancers. Massively parallel next generation sequencing platforms like DNA nanoball sequencing may contribute to the diagnosis and treatment of many genetic diseases. The cost of sequencing an entire human genome has fallen from about one million dollars in 2008, to $4400 in 2010 with the DNA nanoball technology. Sequencing the entire genomes of patients

neg: Mutation (genetic algorithm) is preserving and introducing diversity. Mutation should allow the algorithm to avoid local minima by preventing the population of chromosomes from becoming too similar to each other, thus slowing or even stopping evolution. This reasoning also explains the fact that most GA systems avoid only taking the fittest of the population in generating the next but rather a random (or semi-random) selection with a weighting toward those that are fitter. For different genome types, different mutation types are suitable: This mutation operator takes the chosen genome and inverts the bits (i.e. if the genome bit is 1, it is changed

neg: Epigenetics of diabetes Type 2 the C677t mutation. This is not a spontaneous mutation; it is actually hereditary. While the mutation does not inactivate the gene, it greatly reduces the efficiency, thus impairing the formation of methionine. The lack of this amino acid prevents methylation from occurring, and as said above, hypomethylation leads to increased susceptibility to Type 2 Diabetes. Type 2 diabetes associated sequence polymorphisms have been identified in 30 linkage disequilibrium (LD) blocks across the human genome, but their effects only explain a minor fraction of the observed phenotypic diversity among individuals. Previously, in other studies it has been demonstrated that connections between

neg: Mutation populations less likely to interbreed, thereby preserving genetic differences between these populations. Sequences of DNA that can move about the genome, such as transposons, make up a major fraction of the genetic material of plants and animals, and may have been important in the evolution of genomes. For example, more than a million copies of the Alu sequence are present in the human genome, and these sequences have now been recruited to perform functions such as regulating gene expression. Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing

neg: Human genome Human genome <section begin=lead />The human genome is the complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome, and the mitochondrial genome. Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells (the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote) consist of three billion DNA base pairs, while diploid genomes (found

neg: Leptin to be changed to produce a stop codon, which is much less likely to happen. A recessive frameshift mutation resulting in a reduction of leptin has been observed in two consanguineous children with juvenile obesity. A Human Genome Equivalent (HuGE) review in 2004 looked at studies of the connection between genetic mutations affecting leptin regulation and obesity. They reviewed a common polymorphism in the leptin gene (A19G; frequency 0.46), three mutations in the leptin receptor gene (Q223R, K109R and K656N) and two mutations in the "PPARG" gene (P12A and C161T). They found no association between any of the polymorphisms and

neg: Adaptive evolution in the human genome proportion (9.7%) of positively selected genes were associated with diseases. This may be because diseases can be adaptive in some contexts. For example, schizophrenia has been linked with increased creativity (Crespi et al. 2007), perhaps a useful trait for obtaining food or attracting mates in Palaeolithic times. Alternatively, the adaptive mutations may be the ones which reduce the chance of disease arising due to other mutations. However, this second explanation seems unlikely, because the mutation rate in the human genome is fairly low, so selection would be relatively weak. 417 genes involved in the immune system showed strong evidence of

neg: Haplogroup G (Y-DNA) by country Gnostic Druze, G was found in 4% of 37 samples on the Golan Heights; in 14% of 183 samples in the Galilee; and in 12% of 35 samples in the Carmel. Another study which sampled 20 Druze men apparently living in Israel, none had the G mutation. Among Palestinians apparently living in Israel, 75% of 20 samples were found to be G2a (P15+). In the same study, among Samaritans in Israel none of 12 samples was G. In the Human Genome Diversity Cell Line Panel (CEPH-HDGP) "Central Israel" Palestinian sample (n=17), 59% (10) were G. A study of 329 Druze

neg: Drisapersen Drisapersen Drisapersen (also known as Kyndrisa, PRO051 and GSK2402968) is an experimental drug that was under development by BioMarin, after acquisition of Prosensa, for the treatment of Duchenne muscular dystrophy. The drug is a 2'-O-methyl phosphorothioate oligonucleotide that alters the splicing of the dystrophin RNA transcript, eliminating exon 51 from the mature dystrophin mRNA. Duchenne muscular dystrophy (DMD) is caused when a mutation in the dystrophin gene changes the RNA so that it no longer codes for functional dystrophin protein. This usually happens due to a mutation that alters the reading frame of the RNA downstream of the mutation, so-called

neg: Disposable soma theory of aging of aging. One study found that the cells of short-living rodents "in vitro" show much greater mutation rates and a general lack of genome surveillance compared to human cells and are far more susceptible to oxidative stress. Other studies have been conducted on the naked mole rat, a rodent species with remarkable longevity (30 years), capable of outliving the brown rat (3 years) by ten-fold. Additionally, almost no incidence cancer has ever been detected in naked mole rats. Nearly all of the differences found between these two organisms, which are otherwise rather genetically similar, was in somatic maintenance. Naked mole

neg: Ezutromid open-label trial is enrolling 40 boys, ages 5–10, living in the U.K. or U.S. MRI leg muscle change will be measured as well as ezutromid plasma concentration levels, with a secondary goal of obtaining quantifiable images of utrophin membrane stained biopsies at baseline and either 24 or 48 weeks. As of 2016, ataluren was the only approved drug in the EU to treat a specific subpopulation of patients with nmDMD, or DMD caused by a nonsense mutation. However, nonsense mutations only account for approximately 15% of all patients with DMD. Therefore, Summit Therapeutics projects to file for regulatory approval in

neg: Neoplasm have about 60 to 70 protein altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations However, the average number of DNA sequence mutations in the entire genome (including non-protein-coding regions) within a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. This compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans. The high

neg: Mutation rate mutations have fitness effects. As an example, mutation rates have been directly inferred from the whole genome sequences of experimentally evolved replicate lines of "Escherichia coli" B. A particularly labor-intensive way of characterizing the mutation rate is the mutation accumulation line. Mutation accumulation lines have been used to characterize mutation rates with the Bateman-Mukai Method and direct sequencing of e.g. intestinal bacteria, round-worms, yeast, fruit flies, small annual plants. Mutation rates differ between species and even between different regions of the genome of a single species. These different rates of nucleotide substitution are measured in substitutions (fixed mutations) per base

neg: Mutation rate influence of the genetic context on the mutation rate. There are several natural units of time for each of these rates, with rates being characterized either as mutations per base pair per cell division, per gene per generation, or per genome per generation. The mutation rate of an organism is an evolved characteristic and is strongly influenced by the genetics of each organism, in addition to strong influence from the environment. The upper and lower limits to which mutation rates can evolve is the subject of ongoing investigation. However, the mutation rate does vary over the genome. Over DNA, RNA

neg: SH2B3 is involved in the mechanism of T cell-negative regulation. In addition to its role in progenitor cell growth and commitment, LNK appears to be involved in cell motility and cellular interactions. LNK modulates crosstalk between integrin- and cytokine-mediated signals, thus controlling thrombopoiesis. LNK facilitates integrin aIIbb3 phosphorylation and signaling in order to promote platelet cytoskeleton rearrangement and spreading, and thus stabilizes thrombosis formation. SH2B3 has been shown to interact with Filamin. In humans, genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the SH2B3 gene

neg: No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing has vastly improved efficiency over previous technologies and allows for almost any kind of mutation with ease. These advantages make the CRISPR/Cas9 recombination technique the most promising for application in human health. However, major drawbacks exist, including, most prominently, off-target cleavage that can result in unintended genome disruptions. Reisch and Prather pioneered a technique that combines both the λ-red and CRISPR/Cas9 recombination systems to form a novel methodology called no-SCAR (Scarless Cas9 Assisted Recombineering) for "E. coli" genome modifications. In this method, a plasmid containing the gene for Cas9 expression ("cas9") is first transformed into "E. coli" cells. After selecting

neg: Horse genome Horse genome The horse genome was first sequenced in 2006. The Horse Genome Project mapped 2.7 billion DNA base pairs, and released the full map in 2009. The horse genome is larger than the dog genome, but smaller than the human genome or the bovine genome. It encompasses 31 autosomes and two sex chromosomes. As horses share over 90 hereditary diseases similar to those found in humans, the sequencing of the horse genome has potential applications to both equine and human health. Further, nearly half of the chromosomes in the horse genome show conserved synteny with a human chromosome, far

neg: Joseph Borg (scientist) Joseph Borg (scientist) Joseph Borg (born 27 July 1982) is a Maltese biomedical scientist. He is the group leader of the Borg research group at the Centre for Molecular Medicine and Biobanking, at the University of Malta. He has worked on the Maltese Genome Project. Borg was educated at the University of Malta where he was awarded a PhD in 2010 for research on haemoglobin genes supervised by Alex E. Felice. His thesis was entitled "A Novel Mutation in the Human erythroid transcription factor KLF1 as a cause of hereditary persistence of foetal haemoglobin". His work is focused on the

neg: Human vestigiality structures in humans, which are no longer in use but may indicate common ancestry with other species. One example of this is L-gulonolactone oxidase, a gene that is functional in most other mammals and produces an enzyme that synthesizes vitamin C. In humans and other members of the suborder Haplorrhini, a mutation disabled the gene and made it unable to produce the enzyme. However, the remains of the gene are still present in the human genome as a vestigial genetic sequence called a pseudogene. Human vestigiality In the context of human evolution, human vestigiality involves those traits (such as organs

neg: Suppressor mutation upon infection, an amber mutant defective in a gene encoding a needed structural component of phage T4 is weakly suppressed (in an "E. coli" host containing a specific altered tRNA – see nonsense suppressor), it will produce a reduced number of the needed structural component. As a consequence few if any viable phage are formed. However, it was found that viable phage could sometimes be produced in the host with the weak nonsense suppressor if a second amber mutation in a gene that encodes another structural protein is also present in the phage genome. It was found that the reason

neg: Human genome the environment and the genome. Human genome <section begin=lead />The human genome is the complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome, and the mitochondrial genome. Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells (the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote) consist of three billion DNA base

neg: Causes of autism An expansion of the CGG trinucleotide repeat in the promoter of the gene "FMR1" in boys causes fragile X syndrome, and at least 20% of boys with this mutation have behaviors consistent with autism spectrum disorder. Mutations that inactivate the gene "MECP2" cause Rett syndrome, which is associated with autistic behaviors in girls, and in boys the mutation is embryonic lethal. Besides these early examples, the role of "de novo" mutations in ASD first became evident when DNA microarray technologies reached sufficient resolution to allow the detection of copy number variation (CNV) in the human genome. CNVs are the most

neg: Human mitochondrial molecular clock of the Holocene 11,000 years ago. Parallel mutation (sometimes referred to as Homoplasy) or convergent evolution occurs when separate lineages have the same mutation independently occur at the same site in the genome. Saturation occurs when a single site experiences multiple mutations. Parallel mutations and saturation result in the underestimation of the mutation rate because they are likely to be overlooked. Individuals affected by heteroplasmy have a mixture of mtDNA types, some with new mutations and some without. The new mutations may or may not be passed down to subsequent generations. Thus the presence of heteroplasmic individuals in a sample

neg: Heteroplasmy organism, with each mutation found in about 1–2% of all mitochondrial genomes. In order for heteroplasmy to occur, organelles must contain a genome and, in turn, a genotype. In animals, mitochondria are the only organelles that contain their own genomes, so these organisms will only have mitochondrial heteroplasmy. In contrast, photosynthetic plants contain mitochondria and chloroplasts, each of which contains plastid genomes. Therefore, plant heteroplasmy occurs in two dimensions. In 1909, while studying chloroplast genomes, Erwin Baur made the first observations about organelle inheritance patterns. Organelle genome inheritance differs from nuclear genome, and this is illustrated by four violations of

neg: Paroxysmal kinesigenic choreoathetosis identified in the genome of one family and an insertion mutation identified in the genome of another family. The researchers then confirmed this gene as the cause of PKD when it was not mutated in the genome of 1000 control patients. Researchers found PRRT2 mutations in 10 of 29 sporadic cases affected with PKD, thus suggests PRRT2 is the gene mutated in a subset of PKD and PKD is genetically heterogeneous. The mechanism of how PRRT2 causes PKD still requires further investigation. However, researchers suggest it may have to do with PRRT2's expression in the basal ganglia, and the expression

neg: Error catastrophe of information lost through mutation must be less than the amount gained through natural selection. This fact can be used to arrive at essentially the same equations as the more common differential presentation. The information lost can be quantified as the genome length "L" times the replication error rate "q". The probability of survival, "S", determines the amount of information contributed by natural selection— and information is the negative log of probability. Therefore, a genome can only survive unchanged when For example, the very simple genome where "L = 1" and "q = 1" is a genome with one bit

neg: Off-target genome editing genome also requires a reference genome to make inferences. The easiest way to detect and quantify off-target mutations would be to screen for DSBs in the genome. BLESS or direct "in situ" breaks labeling enrichment on streptavidin. Developed in 2013, BLESS is performed by ligating the DSB ends with biotin i.e. biotinylation. This is followed by separation/collection of said ligated ends using streptavidin. A linked sequence is added to the biotinylated sequences and this final mix is then sequenced to yield the position of the off target mutation. Being unbiased in nature, BLESS gives information about site of mutation within