In  genetics ,  rs16891982 , also known as  F374L , is the name for a  single nucleotide polymorphism  found in the  SLC45A2  gene. The SNP consists of two alleles: C ( cytosine ) and G ( guanine ). [ 2 ]  It is associated with skin tone and hair/eye color. It is a type of  missense mutation . [ 3 ]


C allele homozygosity is associated with black hair in people of European descent, although those with this genotype are usually of non-European descent. [ 2 ]


C/G allele heterozygosity is associated with black hair in people of European descent [ 2 ]


G allele homozygosity is associated with light skin, hair, and eye color (European ancestry), [ 4 ] [ 5 ]  those with this genotype also have a slightly higher susceptibility to  melanoma . [ 3 ]


The  Scenedesmus obliquus   mitochondrial code  (translation table 22) is a  genetic code  found in the  mitochondria  of  Scenedesmus obliquus , a species of  green algae . [ 1 ]


This article incorporates text from the  United States National Library of Medicine , which is in the  public domain .
 [ 2 ]


Scientists Under Attack: Genetic Engineering in the Magnetic Field of Money  ( German :  Gekaufte Wahrheit – Gentechnik im Magnetfeld des Geldes ) [ 1 ]  is a 2009 German documentary film by  Bertram Verhaag  [ de ] . It alleges that the biotechnology industry was implicit in ruining the careers of   Árpád Pusztai  and  Ignacio Chapela  when they published research critical of  genetic engineering .


The film premiered at the 2009  International Documentary Film Festival Amsterdam . [ 2 ]


The 2009 documentary interviewed three scientists ( Árpád Pusztai ,  Nina Fedoroff  and  Ignacio Chapela ) and an attorney (Andrew Kimbrell). Pusztai was a biochemist who went to the media with unpublished research claiming that a type of  genetically modified potato  suppressed the immune system and stunted growth when fed to rats. The resulting  controversy  led to him being fired from the  Rowett Institute . Fedoroff is a highly decorated molecular biologist who is an external adviser to the  US Department of State .  Chapela  is a professor at the  University of Berkeley  and Kimbrell is the executive director of the  Center for Food Safety  who sued the FDA in 1998 over its regulation of GM foods.


The German  ARD  cultural magazine "titel thesen temperamente" broadcast a 6-minute review about the film. [ 3 ]  The  Bayerischer Rundfunk  described the film as committed, partisan and disputatious. [ 4 ]  KinoZeit calls it an ambitious documentary. [ 5 ]


The documentary received 8 international prizes, including three for best documentary. [ 4 ] [ dead link  ]  It won 1st prize at Indie Fest 2010 in the feature documentary category. [ 6 ]


This article about a scientific  documentary  film is a  stub . You can help Wikipedia by  expanding it .


Segregating sites  are positions which show differences ( polymorphisms ) between related genes in a  sequence alignment  (are not  conserved ). [ 1 ]  Segregating sites include  conservative , semi-conservative and non-conservative mutations.


The proportion of segregating sites within a gene is an important statistic in  population genetics  since it can be used to estimate  mutation rate  assuming no  selection . For example it is used to calculate the  Tajima's D  neutral evolution statistic.


In  genetics , a  sense strand,  or  coding strand , is the segment within double-stranded  DNA  that carries the translatable code in the  5′  to   3′   direction, and which is complementary to the  antisense strand  of DNA, or template strand, which does not carry the translatable code in the 5′ to 3′ direction. [ 1 ]  The sense strand is the strand of DNA that has the same sequence as the  mRNA , which takes the  antisense strand  as its template during  transcription , and eventually undergoes (typically, not always)  translation  into a protein. The antisense strand is thus responsible for the RNA that is later translated to protein, while the sense strand possesses a nearly identical makeup to that of the mRNA.


Note that for each segment of double-stranded DNA, there will possibly be two sets of sense and antisense, depending on which direction one reads (since sense and antisense is relative to perspective). It is ultimately the gene product, or mRNA, that dictates which strand of one segment of dsDNA we call sense or antisense. But keep in mind that sometimes, such as in prokaryotes, overlapping genes on opposite strands means the sense for one mRNA can be the antisense for another mRNA. [ 2 ]


The immediate product of this transcription is a resultant initial RNA transcript, which contains a sequence of nucleotides that is identical to that of the sense strand. The exception to this is that  uracil  is used for nucleotide sequencing of RNA molecules rather than  thymine .


Most  eukaryotic  RNA transcripts undergo  additional editing  prior to being translated for protein synthesis. This process typically involves the addition of a methylated  guanine  nucleotide  cap  at the 5' end, the addition of a  poly-A tail  at the 3' end, and the removal of  introns  from the initial RNA transcript ( RNA splicing ). The end product is known as a mature  mRNA . Prokaryotic mRNA does not undergo the same process.


Strictly speaking, only the mRNA makes "sense" with the genetic code, as the translated protein  peptide sequence  can be directly inferred from this strand. The "antisense" strand of DNA is complementary to the "sense" strand and is the actual template for mRNA synthesis.


Knowing the difference between the sense and antisense strands is important in certain molecular biology applications.  For example, in  microarray  expression technologies, it is important to know which strand is "viewed" on the array.  An array can correspond to either strand; however, a single array will be made entirely of "sense" or "antisense" strands.


Identifying the different strands is also important in understanding  small interfering RNAs , or siRNA.


Shadow enhancers  are groups of two or more  enhancers  that control the same target  gene  and drive overlapping spatiotemporal expression patterns. [ 1 ] [ 2 ] [ 3 ]  Shadow enhancers are found in a wide range of organisms, from  insects  to  plants  to  mammals , particularly in association with  developmental genes . [ 4 ] [ 5 ] [ 6 ] [ 7 ]  While seemingly redundant, the individual enhancers of a shadow enhancer group have been shown to be critical for proper  gene expression  in the face of both environmental and genetic perturbations. Such perturbations may exacerbate fluctuations in upstream regulators. [ 1 ] [ 8 ] [ 9 ]


Signature-tagged mutagenesis  ( STM ) is a  genetic  technique used to study  gene  function. Recent advances in  genome sequencing  have allowed us to catalogue a large variety of organisms' genomes, but the function of the genes they contain is still largely unknown. Using STM, the function of the product of a particular gene can be inferred by disabling it and observing the effect on the organism. The original and most common use of STM is to discover which genes in a  pathogen  are involved in  virulence  in its  host , to aid the  development  of new medical therapies/drugs.


The gene in question is inactivated by  insertional   mutation ; a  transposon  is used which inserts itself into the gene sequence. When that gene is  transcribed  and  translated  into a protein, the insertion of the transposon affects the protein structure and (in theory) prevents it from functioning. In STM, mutants are created by random transposon insertion and each transposon contains a different 'tag' sequence that uniquely identifies it. If an insertional mutant bacterium exhibits a  phenotype  of interest, such as susceptibility to an  antibiotic  it was previously  resistant  to, its genome can be sequenced and searched (using a computer) for any of the tags used in the experiment. When a tag is located, the gene that it disrupts is also thus located (it will reside somewhere between a start and stop  codon  which mark the boundaries of the gene).


STM can be used to discover which genes are critical to a pathogen's virulence by injecting a 'pool' of different random mutants into an  animal model  (e.g. a mouse infection model) and observing which of the mutants survive and proliferate in the host. Those mutant pathogens that  don't  survive in the host must have an inactivated gene, required for virulence. Hence, this is an example of a negative selection method.


Sim4  is a  nucleotide   sequence alignment  program akin to  BLAST  but specifically tailored to  DNA  to  cDNA / EST  (Expressed Sequence Tag) alignment (as opposed to DNA–DNA or protein–protein alignment). It was written by Florea et al.


Single molecule fluorescent sequencing  is one method of  DNA  sequencing. The core principle is the imaging of individual  fluorophore  molecules, each corresponding to one base. [ 1 ]  By working on single molecule level,  amplification  of DNA is not required, avoiding amplification bias. The method lends itself to parallelization by probing many sequences simultaneously, imaging all of them at the same time.


The principle can be applied stepwise (e.g. the  Helicos  implementation), or in real time (as in the  Pacific Biosciences  implementation). [ 2 ]


Small Cajal body-specific RNAs  ( scaRNAs ) are a class of  small nucleolar RNAs  (snoRNAs) that specifically localise to the  Cajal body , a  nuclear   organelle  (cellular sub-organelle) involved in the biogenesis of  small nuclear ribonucleoproteins  (snRNPs or snurps).  ScaRNAs guide the  modification ( methylation  and  pseudouridylation ) of  RNA polymerase II   transcribed   spliceosomal  RNAs  U1 ,  U2 ,  U4 ,  U5  and  U12 .


The first scaRNA identified was U85. [ 1 ]  It is unlike typical snoRNAs in that it is a composite C/D box and H/ACA box snoRNAs and can guide both pseudouridylation and 2′- O -methylation. Not all scaRNAs are composite C/D and H/ACA box snoRNA and most scaRNAs are structurally and functionally indistinguishable from snoRNAs, directing  ribosomal RNA  (rRNA) modification in the  nucleolus .


Several studies identified scaRNAs in  Drosophila . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]   One of the studies showed that several  Drosophila  scaRNAs  could function equally well in the nucleoplasm of mutant flies that lack Cajal bodies. [ 4 ]  Further investigation showed that scaRNA pugU6-40 targets U6 snRNA, whose modification occurs in the nucleolus not CB and that  pugU1-6 and pug U2-55 guide 2 RNAs:  snRNA and 28s rRNA. [ 5 ]


In  molecular biology , Small Cajal body-specific RNA 1 (also known as SCARNA1 or ACA35) is a small nucleolar RNA found in Cajal bodies and believed to be involved in the pseudouridylation of U2 spliceosomal RNA at residue U89.


scaRNA1 is a  non-coding RNA , which are functional products of  genes  not  translated  into  proteins .  Such RNA molecules usually contain important  secondary structure  or ligand- binding motifs  and are involved in many important biological processes in the cell. [ 6 ]


scaRNA1 belongs to the  H/ACA box  class of snoRNAs, as it has the predicted hairpin-hinge-hairpin-tail structure, conserved H/ACA-box motifs, and is found associated with  GAR1  protein. [ 7 ]


SNPlex  is a platform for  SNP genotyping  sold by  Applied Biosystems  (ABI).  It is based on  capillary electrophoresis  to separate varying fragments of  DNA , which allows the assay to be performed on ABI's 3730xl  DNA analyzers .  Currently, up to 48  SNPs  can be genotyped in a single reaction. [ 1 ]


The  Social Science Genetic Association Consortium , abbreviated  SSGAC , is a consortium of scientists dedicated to studying the role of  genetics  in important life outcomes in the  social sciences . It has received media coverage for its research looking for  genetic variants  associated with  educational attainment . [ 1 ] [ 2 ]  For instance, the Consortium's first study, published in 2013, found three such variants in a sample of 101,000 people. [ 3 ]


The SSGAC was founded by Daniel Benjamin ( University of Southern California ),  David Cesarini  ( New York University ), and Philipp Koellinger ( VU Amsterdam ). [ 1 ]  According to Benjamin, "One major impetus for the formation of the SSGAC was the growing recognition that most effects of individual genetic markers on behavioral traits are very small and that, consequently, very large samples are required to accurately detect them". [ 4 ]  It was founded during a meeting of the  Cohorts for Heart and Aging Research in Genomic Epidemiology  (CHARGE) consortium on February 12, 2011. The SSGAC continues operates with support from CHARGE. [ 5 ]


Soft rot  Enterobacteriaceae  ( SRE ) (spanning the genera  Erwinia ,  Pectobacterium ,  Dickeya ,  and  Pantoea ), are ubiquitous necrotrophic bacterial pathogens that infect a large number of different plant species worldwide, including economically important crops. [ 1 ] [ 2 ]


When they live in soil outside of their plant hosts they starve and have to adapt to this new condition.  By using strand-specific RNA-seq analysis and  in silico  sRNA predictions 137  small RNAs  candidates were identified in  Pectobacterium atrosepticum  under starvation conditions. This suggests that sRNAs play roles in bacterial adaptive response. The expression of 9 novel candidate sRNAs was validated by RT-PCR. Those included  antisense RNAs   and  UTR  regions. [ 3 ]


A  somatic epitype  is a non-heritable  epigenetic  alteration in a gene.  It is similar to conventional epigenetics in that it does not involve changes in the  DNA  primary sequence.  Physically, the somatic epitype corresponds to changes in DNA  methylation , oxidative damage (replacement of  GTP  with oxo-8-dGTP), or changes in DNA- chromatin  structure that are not reversed by normal cellular or nuclear repair mechanisms.  Somatic epitypes alter gene expression levels without altering the amino acid sequence of the expressed protein.  Current research suggests that somatic epitypes can be altered both before and after birth, and this alteration can be in response to exposure to heavy metals (such as  lead ), differences in maternal care, or nutritional or behavioral stress.  There is no indication that somatic epitypes are heritable in a conventional epigenetic fashion.  Some research suggests that methylation levels (and gene expression) can be reversed for some somatic epitypes by alterations in environmental factors such as diet.


SOS box  is the  operator  to which the  LexA   repressor  binds to repress the  transcription  of SOS-induced proteins. SOS boxes are found near the  promoter  of various  genes . [ 1 ]


LexA binds to an SOS box in the absence of  DNA damage . In the presence of DNA damage the binding of  LexA  is inactivated by the  RecA   activator . SOS boxes differ in DNA sequences and binding affinity towards  LexA  from organism to organism. [ 2 ]  Furthermore, SOS boxes may be present in a dual fashion, which indicates that more than one SOS box can be within the same promoter. [ 3 ]


See  Nucleic acid nomenclature  for an explanation of non-GATC nucleotide letters.


Spacer DNA   is a region of  non-coding DNA  between  genes . [ 1 ] [ 2 ]  The terms  intergenic spacer  ( IGS ) or  non-transcribed spacer  ( NTS ) are used particularly for the spacer DNA between the many  tandemly repeated  copies of the  ribosomal RNA  genes. [ 3 ]


In  bacteria , spacer DNA sequences are only a few  nucleotides  long. In  eukaryotes , they can be extensive and include  repetitive DNA , comprising the majority of the  DNA  of the  genome . [ 3 ]  In  ribosomal DNA , there are spacers within and between gene clusters, called  internal transcribed spacer  (ITS) and  external transcribed spacers  (ETS), respectively. In  animals , the  mitochondrial DNA  genes generally have very short spacers. In  fungi , mitochondrial DNA spacers are common and variable in length, and they may also be mobile. [ 1 ]


Due to the non-coding nature of spacer DNA, its nucleotide sequence changes much more rapidly over time than nucleotide sequences coding for genes that are subject to  selective  forces. Although spacer DNA might not have a  function  that depends on its  nucleotide sequence , it may have sequence-independent functions. [ 2 ]


Spacer DNA has practical applications that enable researchers and scientists to examine interactions between  CRISPR  proteins and  bacteriophages . [ 4 ]


A  split  in  phylogenetics  is a bipartition of a set of  taxa , and the smallest unit of information in unrooted  phylogenetic trees : each edge of an unrooted phylogenetic tree represents one split, and the tree can be efficiently reconstructed from its set of splits. Moreover, when given several trees, the splits occurring in more than half of these trees give rise to a consensus tree, and the splits occurring in a smaller fraction of the trees generally give rise to a consensus  split network . Pairs of splits are  compatible  if any of the subsets defined by each split do not overlap. [ 2 ]


For a given set of  taxa , and a set of  splits  S on the taxa, usually together with a non-negative weighting, which may represent character changes distance, or may also have a more abstract interpretation, if the set of splits S is compatible, then it can be represented by an unrooted  phylogenetic tree  and each edge in the tree corresponds to exactly one of the splits. More generally, S can always be represented by a  split network , [ 1 ]  which is an unrooted  phylogenetic network  with the property that every split in S is represented by an array of parallel edges in the network.


Stem cell chip  is a device that detects given biochemical changes in  stem cells , for example changes in  RNA  expression. [ 1 ]


Sterility  is the  physiological  inability to effect  sexual reproduction  in a living thing, members of whose kind have been produced sexually. Sterility has a wide range of causes. It may be an  inherited trait , as in the mule; or it may be acquired from the environment, for example through  physical injury  or  disease , or by exposure to  radiation .


Sterility is the inability to produce a biological child, while  infertility  is the inability to conceive after a certain period. [ 1 ]  Sterility is rarely discussed in clinical literature and is often used synonymously with infertility. Infertility affects about 12-15% of couples globally. [ 2 ]  Still, the prevalence of sterility remains unknown.
Sterility can be divided into three subtypes natural, clinical, and hardship. [ 1 ]  Natural sterility is the couple's physiological inability to conceive a child naturally.
Clinical sterility is natural sterility for which treatment of the patient will not result in conception.
Hardship sterility is the inability to take advantage of available treatments due to extraneous factors such as economic, psychological, or physical factors.
Clinical sterility is a subtype of natural sterility, and Hardship sterility is a subtype of Clinical sterility.


Hybrid sterility  can be caused by different closely related species breeding and producing offspring. These animals are usually sterile due to the different numbers of chromosomes between the two parents. The imbalance results in  offspring  that is viable but not  fertile , as is the case with the  mule .


Sterility can also be caused by selective breeding, where a selected trait is closely linked to genes involved in sex determination or fertility. For example, goats breed to be polled (hornless). This results in a high number of intersex individuals among the offspring, which are typically sterile. [ 3 ]


Sterility can also be caused by chromosomal differences within an individual. These individuals tend to be known as genetic  mosaics . Loss of part of a chromosome can also cause sterility due to  nondisjunction .


XX male syndrome  is another cause of sterility, wherein the sexual determining factor on the Y chromosome ( SRY ) is transferred to the X chromosome due to an unequal crossing over. This gene triggers the development of testes, causing the individual to be phenotypically male but genotypically female.


Economic uses of sterility include:


Synovial sarcoma, X breakpoint  (SSX) refers to a group of genes rearranged in  synovial sarcoma . [ 1 ]


They include:


The group also has several associated  pseudogenes , and the interacting protein  SSX2IP .


The translocation t(X;18) creates a fusion of the  SYT  gene(at 18q11) with either  SSX1  or  SSX2  (both at Xp11). Neither SYT, nor the SSX proteins contain DNA-binding domains. Instead, they appear to be transcriptional regulators whose actions are mediated primarily through  protein–protein interactions , with BRM in the case of SYT, and with Polycomb group repressors in the case of SSX.  [ 2 ]


T-cell receptor excision circles  (TRECs) are small circles of  DNA  created in  T-cells  during their passage through the  thymus  as they rearrange their  TCR  genes. [ 1 ]  Their presence indicates maturation of T cells;
TRECs are reduced in  SCID  (severe combined immunodeficiency disease).


Signal joint T-cell receptor excision circles (sjTRECs) might be used as a way to test the age of the individual from a blood sample. [ 2 ]  The detection of sjTRECs can be further used as a diagnostic tool to monitor the thymic output (e.g., following hematopoietic stem cell transplantation or in cases of AIDS). [ 3 ]


t(11;14)  is a  chromosomal translocation  which essentially always involves the  immunoglobulin heavy locus , also known as IGH in the q32 region of chromosome 14, as well as  cyclin D1  which is located in the q13 of chromosome 11 . [ 2 ]  Specifically, the translocation is at t(11;14)(q13;q32). [ 3 ] [ 4 ]


The translocation is mainly found in  mantle cell lymphoma , but also in  B-cell prolymphocytic leukemia , in  plasma cell leukemia , in  splenic lymphoma with villous lymphocytes , in  chronic lymphocytic leukemia , and in  multiple myeloma . All these diseases involve B-lineage lymphocytes. [ 2 ]


In multiple myeloma, t(11;14) is a neutral prognostic factor in general, but it may confer a worse prognosis for overall survival in African American people with multiple myeloma. [ 5 ]


T790M , also known as  Thr790Met , is a gatekeeper  mutation  of the  epidermal growth factor receptor  (EGFR). The mutation substitutes a  threonine  (T) with a   methionine  (M) at position 790 of  exon  20, [ 1 ]  affecting the  ATP   binding pocket  of the EGFR kinase domain. Threonine is a small  polar   amino acid ; methionine is a larger nonpolar amino acid. Rather than directly blocking inhibitor binding to the active site, T790M increases the affinity for ATP so that the inhibitors are outcompeted; irreversible covalent inhibitors such as  osimertinib  can overcome this resistance. [ 2 ]   [ 3 ]


Over 50% of acquired resistance to EGFR  tyrosine kinase inhibitors  (TKI) is caused by a  mutation  in the ATP binding pocket of the EGFR kinase domain involving substitution of a small polar threonine residue with a large nonpolar methionine residue, T790M. [ 4 ] [ 5 ]


In November 2015, the US FDA granted accelerated approval to  osimertinib  (Tagrisso) for the treatment of patients with  metastatic   epidermal growth factor receptor  (EGFR) T790M  mutation -positive  non-small cell lung cancer  (NSCLC), as detected by an FDA-approved test, which progressed on or after EGFR TKI therapy. [ 6 ] [ 7 ]


Tandem exon duplication  is defined as duplication of  exons  within the same  gene  to give rise to the subsequent exon. A complete exon analysis of all genes in  Homo sapiens ,  Drosophila melanogaster , and  Caenorhabditis elegans  has shown 12,291 instances of tandem duplication in exons in  human ,  fly , and  worm . Analysis of the  intronic  region has produced further 4,660 unidentified duplicated exons referred to as unannotated exons. 1,578 of these unannotated exons contained  stop codons  thus not considered potential exons. 35.1% of the unannotated exons were found in the  EST  sequence thus confirming the potential of the presence of these exons in  protein  transcripts. [ 1 ]


Variable number of  tandem repeat locus  ( VNTR  locus) is any  DNA sequence  that exist in multiple copies strung together in a variety of tandem lengths. [ 1 ]  The number of repeat copies present at a locus can be visualized by means of a Multi-locus or  Multiple Loci VNTR Analysis  ( MLVA ). In short,  oligonucleotide   primers  are developed for each specific tandem repeat locus, followed by  PCR  and  agarose gel electrophoresis . When the length of the repeat and the size of the flanking regions is known, the number of repeats can be calculated. Analysis of multiple loci will result in a  genotype . [ 2 ]


Tandem selection  is a method of  artificial selection  in which useful traits are selected for sequentially. [ 1 ]  For instance, one could select for both increased  milk   yield  and increased  milk fat  content in  cows  via tandem selection by first selecting those with the best of one trait, production of high milk yield, and then when that trait is at a satisfactory level, by starting to select for those cows that produce milk with the greatest milk fat content instead. However, for cows to produce milk with greater fat content, yield may have to go down due to limits of the cows  metabolism . So while cows are being selected based on increased milk fat content, the yield of milk they are producing may also go down, thus reversing the selection process previously performed to increase it.


Therefore, tandem selection has a major disadvantage to other major types of artificial selection for multiple traits, such as  culling  and  index selection , [ 2 ]  as there is a tendency for the last trait to be lost as the next is being selected. [ 3 ]


Targeted analysis sequencing  (sometimes called  target amplicon sequencing ) (TAS) is a  next-generation DNA sequencing  technique focusing on  amplicons  and specific genes. [ 1 ]  It is useful in population genetics since it can target a large diversity of organisms. The TAS approach incorporates  bioinformatics  techniques to produce a large amount of data at a fraction of the cost involved in  Sanger sequencing . TAS is also useful in DNA studies because it allows for amplification of the needed gene area via  PCR , which is followed by next-gen sequencing platforms. Next-gen sequencing use shorter reads 50–400  base pairs  which allow for quicker sequencing of multiple specimens. Thus TAS allows for a cheaper sequencing approach for that is easily scalable and offers both reliability and speed. [ 2 ]


A  taster  is a person, by means of a human genotype, who is able to taste  phenylthiocarbamide  (PTC) and its derivative 6-n- propylthiouracil  (PROP). [ 1 ]  PTC tastes bitter to many people ( tasters ) but is tasteless to others ( non-tasters ). [ 2 ]


About 70% of Caucasians from North America and Western Europe are tasters. The other 30% are non-tasters. Worldwide, fewer Black and Asian persons are non-tasters, and about 50% of indigenous persons from India are non-tasters. [ 1 ]


taveRNA  is a  software suite  for  RNA / DNA  secondary structure.  It is developed in the laboratories for  computational biology  of the School of  Computing Science  at the  Simon Fraser University .  The suite is composed by alteRNA, for RNA density fold computing, inteRNA, for RNA-RNA interaction prediction,  piRNA , for predicting the joint partition function, equilibrium concentration, ensemble energy, and  melting temperature  for two RNA sequences, [ 1 ]  pRuNA, a sequence based  pruning  RNA interaction  search engine , and smyRNA, a  platform independent   C  program novel ab initio  ncRNA  finder.


taveRNA  is not related to the bioinformatics workflow system  Apache Taverna .


TB3Cs2H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of  uridines  to  pseudouridines  of substrate  RNAs . It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the  nucleolus  of the  eukaryotic cell . TB3Cs2H1 is predicted to guide the  pseudouridylation  of LSU5 ribosomal RNA ( rRNA ) at residue Ψ308. [ 1 ]


TB6Cs1H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB6Cs1H1 is predicted to guide the  pseudouridylation  of LSU3 ribosomal RNA ( rRNA ) at residue Ψ380. [ 1 ]


TB6Cs1H3  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB6Cs1H3 is predicted to guide the  pseudouridylation  of SSU ribosomal RNA ( rRNA ) at residue Ψ662. [ 1 ]


TB6Cs2H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB6Cs2H1 is predicted to guide the  pseudouridylation  of SSU ribosomal RNA ( rRNA ) at residue Ψ1101. [ 1 ]


TB8Cs4H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB8Cs4H1 is predicted to guide the  pseudouridylation  of LSU3 ribosomal RNA ( rRNA ) at residue Ψ358. [ 1 ]


TB9Cs1H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB9Cs1H1 is predicted to guide the  pseudouridylation  of LSU3 ribosomal RNA ( rRNA ) at residue Ψ1273 and SSU ribosomal RNA ( rRNA ) at residue Ψ1088. [ 1 ]


TB9Cs2H2  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecules that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) because of its cellular localization in the nucleolus of the eukaryotic cell. It is predicted to guide the  pseudouridylation  of LSU5 ribosomal RNA ( rRNA ) at residue Ψ1412. [ 1 ]


TB9Cs6H2  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB9Cs6H2 is predicted to guide the  pseudouridylation  of LSU5 ribosomal RNA ( rRNA ) at residue Ψ1653. [ 1 ]


TB10Cs3H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB10Cs3H1 is predicted to guide the  pseudouridylation  of SSU ribosomal RNA ( rRNA ) at residue Ψ263. [ 1 ]


TB11Cs3H1  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB11Cs3H1 is predicted to guide the  pseudouridylation  of LSU3 ribosomal RNA ( rRNA ) at residue Ψ1308. [ 1 ]


TB11Cs4H3  is a member of the H/ACA-like class of non-coding RNA ( ncRNA ) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA ( snoRNA ) thus named because of its cellular localization in the nucleolus of the eukaryotic cell.  TB11Cs4H3 is predicted to guide the  pseudouridylation  of LSU3 ribosomal RNA ( rRNA ) at residue Ψ566. [ 1 ]


Terminally redundant   DNA  is DNA that contains repeated sequences at each end called  terminal repeats . These ends are used (e.g. in  virus T4 ) to join the ends of the linear DNA to form a cyclic DNA. [ 1 ]  The term was first coined by Dr. Michael London in 1964.


The  Thermales- rpoB  RNA motif  is a conserved  RNA  structure that was  discovered by bioinformatics . [ 1 ]
Thermales- rpoB  motifs are found in  Thermales .


Thermales- rpoB  motif RNAs likely function as  cis-regulatory elements , in view of their positions upstream of protein-coding  genes , which invariably encode subunits of  RNA polymerase .  Such genes are also believed to be regulated by the  Rhodo-rpoB RNA motif , although these two motifs occur in quite diverged lineages of  bacteria .


The  Thraustochytrium  mitochondrial code  (translation table 23) is a  genetic code  found in the  mitochondria  of the  labyrinthulid   protist   Thraustochytrium aureum . [ 1 ]  The mitochondrial genome was sequenced by the  Organelle Genome Megasequencing Program .


It is the similar to the bacterial code ( translation table 11 ) but it contains an additional stop codon (TTA) and also has a different set of start codons.


Thymidine triphosphate  ( TTP ), also called  deoxythymidine triphosphate  ( dTTP ), [ 1 ]
is one of the four  nucleoside triphosphates  that are used in the  in vivo  synthesis of  DNA .  Unlike the other  deoxyribonucleoside  triphosphates, thymidine triphosphate does not always contain the "deoxy" prefix in its name. [ 2 ]   This is because dTTP does not have a corresponding  ribonucleoside  triphosphate, as the  uridine triphosphate , which lacks thymidine's 5-methylation ,  is used instead.


dTTP is synthesized via the methylation of  dUMP  via  thymidylate synthase .


It can be used by  DNA ligase  to create overlapping "sticky ends" so that protruding ends of opened microbial  plasmids  may be closed up.


Tongue rolling  is the ability to roll the lateral edges of the  tongue  upwards into a tube. The tongue's  intrinsic muscles  allow some people to form their tongues into specific shapes. Rolling the tongue into a tube shape is often described as a  dominant  trait with simple  Mendelian inheritance , and it is commonly referenced in introductory and genetic  biology  courses, although there is some disagreement. [ 1 ]


Prevalence  in human populations varies between 65% and 81%. [ 2 ]


There is no statistically significant  sexual dimorphism  in this trait. A 1940 study by  Alfred Sturtevant  analyzed 282 people of mostly European ancestry and observed that 67.1% of females and 62.9% of males could roll their tongues, and the remaining could not do it. [ 3 ]  A 1980 study with 992 people also found similar percentages, in 66.84% of females and 63.7% of males possessing the ability. [ 4 ]


In some cases, the ability can be learned by practice, more easily by children, but also by adults. For this reason, studies should allow time for individuals to learn this and other abilities. This also indicates that it's not a simple hereditary trait, and there are other factors involved. [ 2 ] [ 3 ] [ 5 ]


In the first paper about this trait as a genetic trait, Sturtevant concluded that the ability "is conditioned at least in part by heredity", and suggests that "it is possible, though not proved, that ability to turn up the edges of the tongue may be due to a single dominant gene, with the fairly frequent occurrence of additional complications". [ 3 ] [ 6 ]  These findings, however, have been questioned.


Several  twin studies  on the issue have been conducted. A 1952 study involving 33 pairs of  identical twins  found that 21% of them were discordant - that is, one of the twins had the ability and the other did not. [ 7 ]  A 1971 study found that identical twins were 18% discordant, and 22% of non-identical twins were discordant, concluding that "hereditary factors strongly influences tongue rolling ability". [ 8 ]  However, a 1975 found that identical twins were 28% discordant, while 31% of non-identical twins were discordant, and concluded that identical twins were no more likely than fraternal twins to both have the same  phenotype  for tongue rolling. [ 9 ]


One explanation for the pattern is that the trait has  incomplete penetrance . That is, not every individual with the genes can  express  the trait. [ 10 ]


Cloverleaf tongue is the ability to fold the tongue in a certain configuration with multiple bends. This trait has been speculated by David D. Whitney in 1950 to be a dominant trait inherited separately from tongue rolling. [ 11 ]


Other tongue ability is folding the tip of the tongue upwards, which has been proposed as a recessive trait in a 1948 study, with possible  epistatic interaction  with the rolling gene. [ 5 ] [ 11 ]


Twisting the tongue has also been studied, which is to rotate the tongue approximately 90 degrees from the plane of the blade, both to the right and to the left. [ 5 ]


A 1980 study analyzed if there was any interaction between  ear wiggling  and tongue rolling, and found it to be the case for males, with men more likely to have both abilities or none, but no interaction was found for females. [ 4 ]


In  This Is Us , an adopted teenager asks strangers to roll their tongues in an attempt to locate his biological family using genetics. [ 12 ]


In the  Powerpuff Girls  episode " Nuthin' Special ", while searching for a unique super power not shared by her sisters, Buttercup finds out she is the only one that can roll her tongue. [ 13 ]


The  traceability of  genetically modified organisms  (GMOs) describes a system that ensures the forwarding of the identity of a GMO from its production to its final buyer. Traceability is an essential prerequisite for the  co-existence  of GM and non-GM foods, and for the freedom of choice for consumers.


Trans-regulatory elements  (TRE) are DNA sequences encoding upstream regulators (ie.  trans-acting factors ), which may modify or  regulate the expression  of distant genes. [ 1 ]   Trans-acting  factors interact with  cis-regulatory elements  to regulate gene expression. [ 2 ]  TRE mediates expression profiles of a large number of genes via trans-acting factors. [ 3 ]  While TRE mutations affect gene expression, it is also one of the main driving factors for evolutionary divergence in gene expression. [ 3 ]


Trans-regulatory elements work through an  intermolecular  interaction between two different molecules and so are said to be " acting in trans ". For example (1) a  transcribed  and  translated   transcription factor  protein derived from the trans-regulatory element; and a (2) DNA  regulatory element  that is adjacent to the regulated gene. This is in contrast to  cis-regulatory elements  that work through an  intramolecular  interaction between different parts of the same molecule: (1) a gene; and (2) an adjacent regulatory element for that gene in the same DNA molecule. Additionally, each trans-regulatory element affects a large number of genes on both alleles, [ 2 ]  while cis-regulatory element is allele specific  [ 1 ] [ 2 ]  and only controls genes nearby.


Exonic  and  promoter  sequences of the genes are significantly more conserved than the genes in cis- and trans- regulatory elements. [ 3 ]  Hence, they have higher resistance to genetic divergence, yet retains its susceptibility to mutations in upstream regulators. [ 3 ]  This accentuates the significance of genetic divergence within species due to cis- and trans-regulatory variants.


Trans- and cis-regulatory elements co-evolved rapidly in large-scale to maintain gene expression. [ 2 ] [ 3 ] [ 4 ]  They often act in opposite directions, one up-regulates while another down-regulates, to compensate for their effects on the exonic and promoter sequences they act on. [ 2 ] [ 3 ]  Other evolutionary models, such as the independent evolution of trans- or cis-regulatory elements, were deemed incompatible in regulatory systems. [ 3 ] [ 5 ]  Co-evolution of the two regulatory elements was suggested to arise from the same lineage. [ 3 ] [ 4 ]


TRE is more evolutionary constraint than cis-regulatory element, suggesting a hypothesis that TRE mutations are corrected by CRE mutations [ 3 ]  to maintain stability in gene expression. This makes biological sense, due to TRE's effect on a broad range of genes and CRE's compensatory effect on specific genes. [ 1 ] [ 2 ]  Following a TRE mutation, accumulation of CRE mutations act to fine-tune the mutative effect. [ 3 ]


Trans-acting factors can be categorized by their interactions with the regulated genes, cis-acting elements of the genes, or the gene products.


DNA binding trans-acting factors regulate gene expression by interfering with the gene itself or cis-acting elements of the gene, which lead to changes in transcription activities. This can be direct initiation of transcription, [ 6 ]  promotion, or repression of transcriptional protein activities. [ 7 ]


Specific examples include:


DNA editing proteins edit and permanently change gene sequence, and subsequently the gene expression of the cell. [ 8 ] [ 9 ]  All progenies of the cell will inherit the edited gene sequence. [ 10 ]  DNA editing proteins often take part in the immune response system of both prokaryotes and eukaryotes, providing high variance in gene expression in adaptation to various pathogens. [ 11 ]


mRNA processing acts as a form of post-transcriptional regulation, which mostly happens in eukaryotes. 3′ cleavage/polyadenylation and 5’ capping increase overall RNA stability, and the presence of 5’ cap allows ribosome binding for translation. RNA splicing allows the expression of various protein variants from the same gene. [ 12 ]


mRNA binding allows repression of protein translation through direct blocking, degradation or cleavage of mRNA. [ 13 ] [ 14 ]  Certain mRNA binding mechanisms have high specificity, which can act as a form of the intrinsic immune response during certain viral infections. [ 15 ]  Certain segmented RNA viruses can also regulate viral gene expression through RNA binding of another genome segment, however, the details of this mechanism are still unclear. [ 16 ]


Transcription factor II D  ( TF II D ) is one of several  general transcription factors  that make up the  RNA polymerase II   preinitiation complex .  RNA polymerase II holoenzyme  is a form of  eukaryotic   RNA polymerase II  that is recruited to the promoters of  protein -coding genes in living cells. It consists of  RNA polymerase II , a subset of general  transcription factors , and  regulatory proteins  known as SRB proteins.  Before the start of  transcription , the transcription Factor II D (TF II D) complex binds to the  core promoter  DNA of the gene through specific recognition of promoter sequence motifs, including the  TATA box ,  Initiator ,  Downstream Promoter , Motif Ten, or Downstream Regulatory elements. [ 1 ]


TF II D is itself composed of TBP and several  subunits  called  TATA-binding protein  Associated Factors ( TBP-associated factors , or  TAFs ). In a test tube, only TBP is necessary for  transcription  at  promoters  that contain a  TATA box . [ 2 ]  TAFs, however, add promoter selectivity, especially if there is no TATA box sequence for TBP to bind to. [ 1 ]  TAFs are included in two distinct complexes, TF II D [ 3 ]  and B-TF II D. [ 4 ]  The TF II D complex is composed of TBP and more than eight TAFs. But, the majority of TBP is present in the B-TF II D complex, which is composed of TBP and TAFII170 ( BTAF1 ) in a 1:1 ratio. [ 5 ]  TF II D and B-TF II D are not equivalent, since transcription reactions utilizing TF II D are responsive to gene specific transcription factors such as SP1, while reactions reconstituted with B-TF II D are not. [ 5 ]


Subunits in the TF II D complex include: [ 2 ]


Transcription factor II F  ( TF II F ) is one of several  general transcription factors  that make up the  RNA polymerase II   preinitiation complex . [ 1 ] [ 2 ] [ 3 ]


TF II F is encoded by the  GTF2F1 ,  GTF2F2 , and  GTF2F2L  genes. [ 4 ] [ 5 ] [ 6 ]


TF II F binds to  RNA polymerase II  when the enzyme is already unbound to any other transcription factor, thus preventing it from contacting DNA outside the  promoter . Furthermore, TF II F stabilizes the RNA polymerase II while it's contacting  TBP  and  TF II B .


Transplant engineering  (or  allograft engineering ) is a variant of genetic organ  engineering  which comprises  allograft ,  autograft  and  xenograft  engineering. In allograft engineering the graft is substantially modified by altering its genetic composition. The genetic modification can be permanent or transient. The aim of modifying the allograft is usually the mitigation of immunological  graft rejection . [ citation needed ]


Transient genetic allograft engineering has been pioneered by  Shaf Keshavjee [ 1 ] [ 2 ]  and Marcelo Cypel at  University Health Network  in  Toronto  by  adenoviral  transduction for  transgenic  expression of the  IL-10  gene. Permanent genetic allograft engineering has first been done by  Rainer Blasczyk  and Constanca Figueiredo at  Hannover Medical School  in  Hanover  by  lentiviral  transduction for knocking down  MHC  expression in pigs (lung)  [ 3 ]  and rats (kidney). [ 4 ]


Tre recombinase  is an experimental  enzyme  that in lab tests has removed  DNA  inserted by  HIV  from infected cells. [ 1 ]  Through  selective mutation ,  Cre recombinase  which recognizes loxP sites are modified to identify HIV  long terminal repeats  (loxLTR) instead. As a result, instead of performing  Cre-Lox recombination , the new enzyme performs recombination at HIV  provirus  sites. [ 2 ]


The structure of Tre in complex with loxLTR has been resolved ( PDB :  5U91 ), allowing for analyzing the roles of individual mutations. [ 3 ]


The  TREC Genomics track  was a workshop held under the auspices of  NIST  for the purpose of evaluating systems for  information retrieval  and related technologies in the  genomics  domain.  The TREC Genomics track took place annually from 2003 to 2007, with some modifications to the task set every year; tasks included  information retrieval ,  document classification ,  GeneRIF  prediction, and  question answering .


TREE-PUZZLE [ 1 ]  is a computer program used to construct  phylogenetic trees  from sequence data by  maximum likelihood  analysis. Branch lengths can be calculated with and without the  molecular clock hypothesis .


The software also implemented likelihood mapping, [ 2 ]  a method to visualize phylogenetic information in datasets, as well as several tests to assess if the likelihoods of trees are significantly worse than those of other trees.


The program's successor is  IQ-TREE . [ 3 ]


The trematode mitochondrial code  (translation table 21) is a  genetic code  found in the  mitochondria  of  Trematoda .


Trisomic rescue  (also known as  trisomy  rescue  or  trisomy zygote rescue ) is a genetic phenomenon in which a fertilized  ovum  containing three copies of a  chromosome  loses one of these chromosomes ( anaphase lag ) to form a  diploid  chromosome complement. [ 1 ]  If both of the retained chromosomes come from the same parent, then  uniparental disomy  results. If the retained chromosomes come from different parents (that is, one copy from each) then there are no phenotypic or genotypic anomalies. The mechanism of trisomic rescue has been well confirmed  in vivo , and alternative mechanisms that occur in trisomies are rare in comparison. [ 2 ]


Many trisomic conditions result in stillborn infants (major exceptions include trisomies  13 ,  18 ,  21 ). Trisomic rescue may be a natural means to keep a fetus as viable as possible (though uniparental disomy may occur and result in syndromes such as  Prader-Willi  and  Angelman  syndromes due to  genetic imprinting ). Indeed, spontaneous trisomic rescue has been observed  in vitro . [ 3 ]  Similarly,  monosomic rescue  may also be a natural means to keep fetal viability via restoration of a disomic zygote.


TrueAllele  is a software program by  Cybergenetics  that analyzes  DNA  using statistical methods, a process called  probabilistic genotyping . It is used in  forensic identification . [ 1 ]  The program can be used in situations unsuited to traditional methods, such as when a mixture of multiple people's DNA is in a sample. [ 2 ]


Some studies, mostly conducted by Cybergenetics' Chief Scientific Officer Mark W. Perlin, have validated the program's accuracy. [ 3 ]  In one study, TrueAllele distinguished between the genetic code of first-degree relatives with "great accuracy". [ 4 ]  The President's Council of Advisors on Science and Technology  has noted that many validation studies were made by people affiliated with TrueAllele and are therefore not independent, demanding more independent research. [ 1 ]  In one case, TrueAllele's results differed from the results of STRMix, another probabilistic genotyping program, leading to the judge rejecting the DNA evidence. [ 1 ]


The proprietary nature of the code has led to concerns over its reliability. Unlike some similar programs, TrueAllele is not  open source , so judges and attorneys cannot check the program's code. [ 1 ]


This  law enforcement –related article is a  stub . You can help Wikipedia by  expanding it .


In  population genetics ,  typostrophic variation  is the type of genetic variation found in peripherally isolated populations. Variation of this kind is  heterogeneous , due to factors such as  geographic isolation  and  inbreeding . In 1954,  Ernst Mayr  wrote a landmark paper developing the idea that  subspecies  in typostophic populations lead to formation of  incipient species . [ 1 ]  According to Mayr, species formation rarely occurred in populations which were exemplified by  ecotypic variation .


UCSC Malaria Genome Browser  is a bioinformatic research tool to study the  malaria  genome, developed by Hughes Undergraduate Research Laboratory together with the laboratory of Prof. Manuel Ares Jr. at the  University of California, Santa Cruz . [ 1 ]


The web interface and database structure is based on the UCSC  Genome Browser . [ 2 ] [ 3 ]  UCSC Malaria Genome Browser brings together on a single screen the full  DNA sequences  of several species of the  malaria parasite  ( Plasmodium sp. ), alongside experimental results and previously discovered genes collected from the literature. The program allows users to search through 14 chromosomes of the malaria parasite's genome, enter their own sequence data and notes, and compare findings across species. The Malaria Genome Browser also supports text and sequence based searches that provide quick, precise access to any region of specific interest in the malaria genome. This site contains the  reference genome  sequence and working draft assembly for  Plasmodium falciparum  from  PlasmoDb , [ 4 ]  the  Plasmodium  genome database build 5.0.


un-24  is a gene in fungus such as  Neurospora crassa , encode  Ribonucleoside-diphosphate reductase  large chain, involved in their  heterokaryon incompatibility . [ 1 ]


un-25  is a gene in  Neurospora crassa , encode a fungus  ortholog  of the human  60S ribosomal protein L13 , is the structural constituent of  ribosome . [ 1 ]


Unique molecular identifiers  ( UMIs ), or  molecular barcodes  ( MBC ) are short sequences or molecular "tags" added to DNA fragments in some  next generation sequencing  library preparation protocols to identify the input DNA molecule. These tags are added before  PCR  amplification, and can be  used to reduce errors and quantitative  bias  introduced by the amplification.


Applications include analysis of unique cDNAs to avoid PCR biases in  iCLIP , [ 1 ]   variant calling  in  ctDNA ,  gene expression  in  single-cell RNA-seq (scRNA-seq) [ 2 ] [ 3 ]  and  haplotyping  via linked reads [ clarification needed ] .


An  upstream open reading frame  ( uORF ) is an  open reading frame  (ORF) within the  5' untranslated region  (5'UTR) of an  mRNA . uORFs can regulate  eukaryotic   gene expression . [ 1 ] [ 2 ]  Translation of the uORF typically inhibits downstream expression of the primary ORF. However, in some genes such as yeast GCN4, translation of specific uORFs may increase translation of the main ORF. [ 3 ]


Approximately 50% of human genes contain uORFs in their 5'UTR, and when present, these cause reductions in protein expression. [ 4 ]  Human  peptides  derived from translated uORFs can be detected from cellular material with a  mass spectrometer . [ 5 ]
uORFs were found in two thirds of proto-oncogenes and related proteins. [ 6 ]


In  bacteria , uORFs are called  leader peptides  and were originally discovered on the basis of their impact on the regulation of genes involved in the synthesis or transport of  amino acids .


Uptake signal sequences  ( USS ) are short  DNA  sequences preferentially taken up by competent  bacteria  of the family  Pasteurellaceae  ( e.g. ,  Haemophilus influenzae ). Similar sequences, called  DNA uptake sequences  (DUS), are found in species of the family  Neisseriaceae  (including  Neisseria meningitidis  and  Neisseria gonorrhoeae ). [ 1 ]


Genetic transformation  is the process by which a recipient bacterial cell takes up naked DNA from its environment and integrates this DNA into the recipient's genome by  recombination .  In  N. meningitidis , DNA transformation requires the presence of short DUS (10-12 mers residing in coding and intergenic regions) of the donor DNA.  Specific recognition of DUSs is mediated by a type IV  pilin . [ 2 ]   Davidsen et al. [ 3 ]  reported that in  N. meningitidis  DUSs occur at a significantly higher density in genes involved in  DNA repair  and  recombination  (as well as in restriction-modification and replication) than in other annotated gene groups.  These authors proposed that the over-representation of DUS in DNA repair and recombination genes may reflect the benefit of maintaining the integrity of the DNA repair and recombination machinery by preferentially taking up genome maintenance genes that could replace their damaged counterparts in the recipient cell's genome.  Uptake of such genes could provide a mechanism for facilitating recovery from DNA damage after  genotoxic  stress.


UvrABC endonuclease  is a multienzyme complex in  bacteria  involved in  DNA repair  by  nucleotide excision repair , and it is, therefore, sometimes called an  excinuclease . This UvrABC repair process, sometimes called the short-patch process, involves the removal of twelve nucleotides where a genetic mutation has occurred followed by a DNA polymerase, replacing these aberrant nucleotides with the correct nucleotides and completing the  DNA repair . The subunits for this enzyme are encoded in the  uvrA ,  uvrB , and  uvrC  genes. This enzyme complex is able to repair many different types of damage, including  cyclobutyl dimer  formation. [ 1 ]


This  EC 3.1   enzyme -related article is a  stub . You can help Wikipedia by  expanding it .


Vacuolar protein sorting proteins  are involved in the intracellular sorting and  delivery  of soluble  vacuolar  proteins. [ 1 ]


The term  vertical resistance , used commonly in the context of plant selection, was first used in 1963 by  James Edward Van der Plank  to describe single-gene resistance. This contrasted with the term  horizontal resistance  which was used to describe many-gene resistance. [ 1 ]


In 1976,  Raoul A. Robinson  adapted the original definition of vertical resistance and argued that in vertical resistance there were individual genes for resistance in the host plant and also individual genes for parasitic ability in the parasite. This phenomenon is known as the  gene-for-gene relationship , and it was the defining character of vertical resistance. [ 2 ]


Very short patch (VSP) repair  is a  DNA repair  system that removes GT mismatches created by the  deamination  of  5-methylcytosine  to  thymine . This system exists because the  glycosylases  which normally target deaminated bases cannot target thymine (it being one of the regular four bases in DNA).


The components of the system are MutS, which binds to the GT mismatch, the VSR endonuclease, which cuts the DNA, and MutL, which recruits the  UvrD  helicase.


VSR (very short patch repair)  endonucleases  occur in a variety of  bacteria . They work by cutting, or rather, making a nick in  DNA  if the  base pair  is mutated or damaged.


Mutations in the base pairs of DNA can be harmful to the organism.  In particular, C to T mutations occur quite often due to methylation of cytosine. Hence, the VSR endonucleases have a function to protect the cell from damage caused by mutated DNA.


VSR recognises a TG mismatched  base  pair, generated after spontaneous  deamination  of  methylated  cytosines, and it creates a nick  on a single strand by  cleaving  the  phosphate  backbone on the  5'  side of the thymine. [ 1 ]  Then  DNA Polymerase  I removes the T and some nucleotides on the 3' strand and then resynthesises the patch. [ 2 ]


Additionally, GT mismatches can lead to C-to-T  transition   mutations  if not  repaired . VSR repairs the mismatches in favour of the G-containing strand. In  Escherichia coli , this  endonuclease  nicks double-stranded DNA within the  sequence  CT(AT)GN or NT(AT)GG next to the  thymidine  residue, which is mismatched to 2'-deoxyguanosine. [ 3 ]  The incision is mismatch-dependent and strand specific.


The  structure  of VSR is similar to the core  structure  of restriction endonucleases, which have a 3-layer alpha/beta/alpha topology. [ 4 ]


VSR has three aromatic residues ( Phe67 ,  Trp68  and Trp86), which intercalate into the  major groove , bending the DNA and separating the two strands. The  N-terminal  domain stabilizes the interaction between the protein and the cleaved product, thereby protecting the nick from  DNA ligase  until the arrival of DNA Polymerase I.


In  statistics , the  W-test  is designed to test the distributional differences between cases and controls for categorical variable set, which can be a single SNP, SNP-SNP, or SNP-environment pairs. It takes a combined log of  odds ratio  form, calculated from the  contingency table  of the variable set. The test inherits a  chi-squared distribution  with data-set adaptive degrees of freedom  f , estimated from smaller  bootstrapped  samples of the data. The flexible and data-corrected probability distribution allows W-test to give relatively accurate p-values under complex genetic architectures.


Theoretically, the test is not restricted to pairwise interactions, and can go to higher order if sample size of the data can support it. The W-test's application for pairwise interaction effect has been tested in common genome-wide association study (GWAS) dataset with less than 5,000 subjects [1].  Since it corrects for probability distribution bias due to sparse data through the bootstrapped parameters, it has persistent power in low frequency variant environment, when the  minor allele frequency  (MAF) of  single-nucleotide polymorphism  (SNP) is between 1% and 5%.


The W-test C++ software, linux version and R package are available from the  wtest official website .


Woodchuck Hepatitis Virus  (WHV) Posttranscriptional Regulatory Element (WPRE)  is a  DNA sequence  that, when transcribed, creates a  tertiary structure  enhancing  expression . The sequence is commonly used in  molecular biology  to increase expression of  genes  delivered by  viral vectors . [ 1 ]  WPRE is a tripartite regulatory element with gamma, alpha, and beta components.  The alpha component is 80bp long:


GCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGT [ 2 ]


When used alone without the gamma and beta WPRE components, the alpha component is only 9% as active as the full tripartite WPRE. The sequence for full tripartite WPRE is:


This sequence has 100%  homology  with base pairs 1093 to 1684 of the  Woodchuck hepatitis B virus  (WHV8) genome. When used in the 3' untranslated region (UTR) of a mammalian  expression cassette , it can significantly increase  mRNA stability  and protein yield. [ 2 ]


Consisting of about 110  amino acids , the domain in  winged-helix transcription factors  (see  Regulation of gene expression ) has four helices and a two-strand  beta-sheet .


These proteins are classified into 19 families called FoxA-FoxS.


Mutations  in FoxP proteins are implicated in human  autoimmune diseases .


X hyperactivation  refers to the process in  Drosophila  by which genes on the X chromosome in male flies become twice as active as genes on the X chromosome in female flies.


Because male flies have a single X chromosome and female flies have two X chromosomes, the higher level of activation in males ensures that X chromosome genes are overall expressed at the same level in males and females. X hyperactivation is one mechanism of  dosage compensation , whereby organisms that use genetic  sex determination systems  balance the gene dosage from the sex chromosomes between males and females. [ 1 ]  X hyperactivation is regulated by the  alternative splicing  of a gene called  sex-lethal . The gene was named  sex-lethal  due to its mutant  phenotype  which has little to no effect on male flies but results in the death of females due to X hyperactivation of the two X chromosomes. In female  Drosophila , the sex-lethal protein causes the female-specific  splicing  of the  sex-lethal gene to produce more of the sex-lethal protein. This produces a  positive feedback loop  as the sex-lethal protein splices the  sex-lethal  gene to produce more of the sex-lethal protein. In male  Drosophila , there isn’t enough sex-lethal to activate the female-specific splicing of the  sex-lethal  gene, and it goes through the "default" splicing. This means that section of the gene that is spliced out in females remains in males. This portion contains an early  stop codon  resulting in no protein being made from it. [ 2 ]  In females, the sex-lethal protein inhibits the  male-specific lethal  ( msl ) gene complex that would normally activate  X-linked genes  that result in an increase in the male  transcription  rate. The  msl  gene complex was named due to the loss-of-function mutant that results in the improper increase in the male transcription rate that results in the death of males. [ 3 ]  In males, the absence of the necessary amount of sex-lethal allows for the increase in the male transcription rate due to the  msl  gene complex no longer being inhibited. This allows the expression of the X chromosome to be "doubled," or hyperactivated, to match the amount that females have with two X chromosomes. [ 4 ]


The second dosage compensation that occurs in mammals are the balancing of X’s and autosomes. This regulation occurs by the upregulation of Xa, which is the active X. The upregulation of the active X shows increases in the activation of transcription and elongation. The X chromosome, compared to an autosomal gene, contains more silent genes which influences measuring the amount of influence active genes have. RNA-seq data was preformed and the autosomal and X linked gene outputs were significantly different. This agrees with the fact that X dosage compensation is in respect to autosomes. The loss of an X chromosome leads to an aneuploidy effect which disrupts the entire cell in  Drosophila . This effect leads to the disruption of MSL (male specific lethal) from binding onto its target site. To overcome this, the X chromosome is first hyperactivated. Then, the hyperactivated X chromosome facilitates the inversion of the aneuploidy effect to create a gene expression equality between males and females. An aneuploidy effect is when the number of chromosomes is increased or decreased from normal. Natural selection occurs efficiently in Drosophila so the genes that are dosage-sensitive are increased. The dosage-sensitive genes vary from species to species.


The  X:A ratio  is the ratio between the number of  X chromosomes  and the number of sets of  autosomes  in an  organism . This ratio is used primarily for determining the sex of some species, such as  drosophila  flies and the  C. elegans  nematode. [ 1 ]  The first use of this ratio for sex determination is ascribed to Victor M. Nigon. [ 1 ]


Generally, a 1:1 ratio results in a female and a 1:2 ratio results in a male. When calculating the ratio,  Y chromosomes  are ignored. For example, for a  diploid  drosophila that has XX, the ratio is 1:1 (2 Xs to 2 sets of autosomes, since it is a diploid). For a diploid drosophila that has XY, the ratio is 1:2 (1 X to 2 sets of autosomes, since it is diploid). [ 2 ]
Drosophilla sex chromosome ratio determines the factors it encodes which enhances the synthesis of sxl protein which in turn activates the female specific pathway.


This article related to members of the fly family  Drosophilidae  is a  stub . You can help Wikipedia by  expanding it .


XL-413  is a drug which acts as a selective inhibitor of the  enzyme   cell division cycle 7-related protein kinase  (CDC7). It is being researched for the treatment of some forms of  cancer , and also has applications in  genetic engineering . [ 1 ] [ 2 ] [ 3 ] [ 4 ]


NM_001172811 NM_001172813 NM_001172814 NM_001172815 NM_173851


NP_001166282 NP_001166284 NP_001166285 NP_001166286 NP_776250


Zinc transporter 8  ( ZNT8 ) is a  protein  that in humans is encoded by the  SLC30A8   gene . [ 5 ]  ZNT8 is a  zinc transporter  related to  insulin  secretion in humans.  In particular, ZNT8 is critical for the accumulation of zinc into beta cell secretory granules and the maintenance of stored insulin as tightly packaged hexamers. Certain  alleles  of the SLC30A8 gene may increase the risk for developing  type 2 diabetes , but a loss-of-function mutation appears to greatly reduce the risk of diabetes. [ 6 ]


Twelve rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150,000 individuals from 5 different ancestry groups. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin. [ 7 ] [ 8 ] [ 9 ]  Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p. Lys34Serfs*50 demonstrated reduced glucose levels. [ 6 ]  Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk. [ 10 ] [ 11 ]  Conversely, loss-of-function mutations in humans indicate that SLC30A8  haploinsufficiency  protects against T2D. Therefore, ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D. [ 6 ]


This  membrane protein –related article is a  stub . You can help Wikipedia by  expanding it .


1p36 deletion syndrome   is a  congenital   genetic disorder  characterized by moderate to severe  intellectual disability , delayed growth,  hypotonia , seizures, limited speech ability, malformations, hearing and vision impairment, and  distinct facial features . The symptoms may vary, depending on the exact location of the chromosomal deletion. [ 1 ]


The condition is caused by a  genetic deletion  (loss of a segment of DNA) on the outermost band on the short arm (p) of  chromosome 1 . It is one of the most common deletion syndromes. The syndrome is thought to affect one in every 5,000 to 10,000 births. [ 2 ]


There are a number of signs and symptoms characteristic of monosomy 1p36, but no one individual will display all of the possible features. In general, children will exhibit  failure to thrive  and global delays. [ 3 ]


Most young children with 1p36 deletion syndrome have  delayed development  of speech and motor skills. Speech is severely affected, with many children learning only a few words or having no speech at all. Behavioral problems are also common, and include temper outbursts, banging or throwing objects, striking people, screaming episodes, and self-injurious behavior (wrist biting, head striking/banging). A significant proportion of affected people are on the  autism spectrum , and many exhibit  stereotypy . [ 3 ] [ 4 ]


Most people with 1p36 deletion syndrome have some structural abnormality of the brain, and approximately half have  epilepsy  or other seizures. [ 4 ] [ 3 ]  Almost all children exhibit some degree of  hypotonia . [ 5 ]  Common structural brain abnormalities include  agenesis of the corpus callosum , cerebral cortical atrophy,  gait abnormalities , and  ventriculomegaly .  Dysphagia ,  esophageal reflux , and other feeding difficulties are also common. [ 3 ]


The most common visual abnormalities associated with 1p36 deletion syndrome include  farsightedness  (hypermetropia),  myopia  (nearsightedness), and  strabismus  (cross-eyes). Less common but still recognized are  blepharophimosis ,  cataracts ,  ocular albinism ,  optic atrophy ,  optic disk pallor , and  optic nerve coloboma . [ 3 ]


The facial features of 1p36 deletion syndrome have been considered to be characteristic, although few patients have been diagnosed solely on the basis of facial appearance. These features may include  microcephaly  (small head), which may be combined with  brachycephaly  (short head); small, deep-set eyes; straight eyebrows; epicanthal folds; a broad, flat nose and nasal bridge; underdevelopment of the midface (midface hypoplasia); a long philtrum; pointed chin; and abnormally shaped, rotated, low-set ears. [ 4 ]  Infants may have a large  anterior fontanelle , or the anterior fontanelle may close late. [ 6 ]


Short feet,  brachydactyly  (short fingers), and  camptodactyly  (permanent flexion of a finger), fifth finger  clinodactyly  (abnormal curvature) and other skeletal anomalies are sometimes found in conjunction with 1p36 deletion. [ 5 ]


These patients may have congenital heart defects ranging from cardiac septal defects to valvular anomalies and tetralogy of Fallot. In particular, some of the patients may have LV noncompaction a form of dilated cardiomyopathy. This form of LV noncompaction cardiomyopathy is thought to be related to the deletion of the gene CASZ1, this gene in mice leads to ventricular noncompaction. [ 7 ] [ 8 ]


1p36 deletion syndrome is caused by the deletion of the most  distal  light band of the short arm of  chromosome 1 . [ 5 ]


The breakpoints for 1p36 deletion syndrome have been variable and are most commonly found from 1p36.13 to 1p36.33. 40 percent of all breakpoints occur 3 to 5 million  base pairs  from the  telomere . The size of the deletion ranges from approximately 1.5 million base pairs to greater than 10 million. [ 9 ]


Most deletions in chromosome 1p36 are  de novo mutations . 20% of patients with 1p36 deletion syndrome inherit the disease from one parent who carries a  balanced or symmetrical translocation . [ 4 ]


1p36 deletion syndrome is usually suspected based on the signs and symptoms and confirmed by  fluorescence in situ hybridization  (FISH). [ 10 ]   Chromosomal microarray  or  karyotype  analysis may also be used to diagnose 1p36 deletion. [ 5 ]


There is no cure for 1p36 deletion syndrome, and treatment is focused on relieving symptoms of the disease. Of particular importance are appropriate medication for endocrine and neurologic manifestations, such as anti-seizure medications. Feeding difficulties can be managed with specialized assistive devices or with a  gastrostomy (feeding) tube . [ 3 ]


1p36 deletion syndrome is the most common terminal deletion syndrome in humans. [ 6 ]  It occurs in between 1 in 5000 and 1 in 10000 live births. [ 4 ]  And only 100 cases have been reported between 1981 and 2015. [ disputed  –  discuss ] [ 11 ]


2p15-16.1 microdeletion  is an extremely rare  genetic disorder  caused by a small deletion in the  short arm  of human  chromosome 2 . First described in two patients in 2007, [ 1 ]  by 2013 only 21 [ citation needed ]  people have been reported as having the disorder in the  medical literature . [ 2 ] [ 3 ] [ 4 ] [ 5 ]


As of 2013, only 21 patients with a 2p15-16.1 microdeletion had been identified. The clinical similarities between the individuals resulted in the classification of a new genetic  syndrome . [ 1 ] [ 2 ] [ 3 ]  The shared clinical features include moderate to severe  intellectual disability  and similar facial features including  telecanthus ,  drooping eyelids , downslanting, short  palpebral fissures , a prominent  nasal bridge , high palate with long, smooth  philtrum  and an everted lower lip. Some of the patients also had feeding problems in infancy,  microcephaly ,  optic nerve hypoplasia  and  hydronephrosis , wide-spaced nipples, short stature,  cortical dysplasia ,  camptodactyly  and  pigeon toe . [ 1 ] [ 2 ] [ 3 ]


Three of the patients reported had a consistent  proximal  breakpoint on chromosome 2, but varying  distal  breakpoints. [ 1 ] [ 2 ]   The patients have 2p15–16.1 deletions of 5.7  megabases  (Mb), 4.5 Mb, 3.9 Mb, 3.35Mb 3.3Mb and 570  kilobases , respectively. [ 4 ]  In all 21 patients the deletions are  de novo  — neither parent possessed nor transmitted the mutation to the affected individual. One patient is a  genetic mosaic , having some cells with the deletion and others without. [ 2 ]


The largest deletion encompasses approximately 15 protein-coding  genes , 6  pseudogenes  and a number of other as yet uncharacterised candidates, including: [ 2 ] [ 6 ]


Unique - Rare Chromosome Disorder Support Group. (2018). 2p15p16.1 microdeletion syndrome.  https://rarechromo.org/media/information/Chromosome%20%202/2p15p16.1%20microdeletion%20syndrome%20FTNW.pdf


3p deletion syndrome  is a rare  genetic disorder  caused by the deletion of small fragments of  chromosome 3 . [ 2 ]


Reports symptoms in patients with 3p deletion syndrome are  intellectual disability ,  delayed psychomotor development , abnormal facial features, muscular  hypotonia ,  epilepsy , and deformation of the gastrointestinal and urinary tracts. [ 3 ]


3p deletion syndrome is brought on by the loss of  chromosome 3 's small (p) arm's end. The majority of 3p deletion syndrome instances are not hereditary. One  chromosome  is deleted, usually randomly, either in the early stages of fetal development or during the production of reproductive cells, such as eggs or sperm. Affected individuals in these situations do not have a family history of the condition. Rarely, 3p deletion syndrome is inherited; typically, it comes from a parent who has modest symptoms. A parent who is unaffected and has a chromosomal rearrangement between  chromosome 3  and another chromosome may potentially pass on the deletion to their offspring. [ 4 ]


Less than 60 cases have been reported as of 2021. [ 3 ]


22q11.2 distal deletion syndrome  is a rare genetic condition caused by a tiny missing part of one of the body's 46 chromosomes –  chromosome 22 . 22q11.2 distal deletion syndrome appears to be a recurrent genomic disorder distinct from  22q11.2 deletion syndrome  also known as DiGeorge syndrome (DGS; 188400) and  velocardiofacial syndrome  (VCFS; 192430). [ 3 ]


The first published description of a person with a 22q11.2 distal deletion was in 1999. [ 4 ]  There have since been hundreds of cases reported worldwide. 22q11.2 distal deletion syndrome seems to occur equally often in males and females. There are reports of people who are unaffected by carrying the deletion and only discovered it after their child was diagnosed. It seems that the 22q11.2 distal deletion can be "silent" and it is unknown how many people may have a silent form of this syndrome.


Every 22q11.2 distal deletion is unique, and each person may have different medical and developmental concerns. A number of common features have emerged: [ citation needed ]


22q11.2 distal deletion occurs spontaneously; there is no known environmental cause. The genetic term for this is  de novo ; both parents typically have normal chromosomes. This is hereditary and people affected by distal deletion syndrome have a 50/50 chance of passing it to their children. [ citation needed ]


De novo 22q11.2 distal deletions are caused by a mistake that is thought to occur when the parents' sperm or egg cells are formed. At one point in the formation, all the chromosomes including the two chromosome 22s pair up and swap segments. To pair up precisely, each chromosome 'recognizes' matching or near-matching DNA sequences on its partner chromosome. However, throughout each chromosome there are many similar DNA sequences that can overlap incorrectly, and pair with the wrong sequence. It is believed that when the exchange of genetic material, known as 'crossing over', occurs after mismatching, it is unequal, looping out and excising a length of the chromosome. [ citation needed ]


The features of 22q11.2 distal deletion syndrome are likely to be the result of the loss of a number of different genes found in this region. Most people have an approximately 0.4 to 2.1 Mb deletion (400'000- 2. Millions bases). Although the gene(s) responsible for the clinical features associated with 22q11.2 distal deletion syndrome have not been clearly defined, several potential candidate genes have been suggested. [ citation needed ]


CRKL  and  MAPK1  genes have been suggested to have a role in the heart anomalies that are common in 22q11.2 distal deletion syndrome. MAPK1 has also been suggested to be associated with placental development and therefore having one copy of this gene missing in 22q11.2 distal deletion syndrome may be linked to the tendency for  premature birth  and  IUGR . [ 5 ]   The MAPK1 gene in mice has been shown to contribute to social behavior [ 6 ]   and therefore may play a role in the behavioral problems found in some people with 22q11.2 distal deletion syndrome.


Very distal deletions including the  SMARCB1  gene are associated with an increased risk of malignant  rhabdoid tumors . Very little is known about the magnitude of the risk for malignancy associated with distal 22q11.2 deletion syndrome but it is advised that people with a deletion that includes the SMARCB1 gene undergo careful, prolonged monitoring for this type of tumor. Most persons with 22q11 distal deletions do not have deletion of the SMARCB1 gene. [ citation needed ]


22q11.2 duplication syndrome  is a rare  genetic disorder  caused by a  duplication  of a segment at the end of  chromosome 22 .


The most frequent reported symptoms in patients with 22q11.2 duplication syndrome are  intellectual disability /learning disability (97% of patients),  delayed psychomotor development  (67% of patients), growth retardation (63% of patients) and muscular  hypotonia  (43% of patients). [ 1 ]  However, these are common and relatively non-specific indications for  cytogenetic  analysis, and the extent to which the duplication of 22q11.2 causes these features is currently unknown.  The duplication is frequently inherited from a normal parent, so it is clear that intellectual development can be normal. [ citation needed ]


Duplications of 22q11 vary in size and thereby in gene content. They include the typical common 3-Mb microduplication, 1.5-Mb nested duplication, consistent with  non-allelic homologous recombination  (NAHR) using distinct low-copy repeats. These microduplications likely represent the predicted reciprocal rearrangements to the microdeletions characterized in the 22q11.2 region. [ 2 ]  Smaller microduplications may occur within this highly dynamic with frequent rearrangements using alternative low-copy repeats  as recombination substrates within and distal to the  DiGeorge syndrome  region. [ citation needed ]


The majority of 22q11 duplications are  inherited  often from a parent with a normal or near-normal  phenotype . This is in sharp distinction to  22q11 deletion syndrome  where about 90% of cases are caused by mutations that occur  de novo . [ citation needed ]


22q13 deletion syndrome ,
known as  Phelan–McDermid syndrome  ( PMS ), is a  genetic disorder  caused by deletions or rearrangements on the q terminal end (long arm) of  chromosome 22 . Any abnormal genetic variation in the q13 region that presents with significant manifestations ( phenotype ) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. [ 1 ]  The Developmental Synaptopathies Consortium defines PMS as being caused by  SHANK3  mutations, a definition that appears to exclude terminal deletions. [ 2 ]  The requirement to include  SHANK3  in the definition is supported by many but not by those who first described 22q13 deletion syndrome. [ 3 ]


Prototypical terminal deletion of 22q13 can be uncovered by  karyotype  analysis, but many terminal and interstitial deletions are too small. The availability of  DNA microarray  technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice. The falling cost for the whole  exome sequencing  and, eventually,  whole genome sequencing , may replace  DNA microarray  technology for candidate evaluation. However,  fluorescence in situ hybridization  (FISH) tests remain valuable for diagnosing cases of  mosaicism  (mosaic genetics) and chromosomal rearrangements (e.g.,  ring chromosome , unbalanced  chromosomal translocation ). Although early researchers sought a monogenic (single gene  genetic disorder ) explanation, recent studies have not supported that hypothesis (see  Etiology ).


Affected individuals present with a broad array of medical and behavioral manifestations (tables 1 and 2). [ 4 ] [ 5 ] [ 6 ] [ 7 ]  Patients are consistently characterized by global developmental delay, intellectual disability, speech abnormalities,  ASD -like behaviors,  hypotonia  and mild  dysmorphic features . [ 4 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  Table 1 summarizes the dysmorphic and medical conditions that have been reported in individuals with PMS. Table 2 summarizes the psychiatric and neurological symptoms associated with PMS. Most of the studies include small samples or relied on parental report or medical record review to collect information, which can account in part for the variability in the presentation of some of the presenting features. Larger prospective studies are needed to further characterize the phenotype.


Various deletions affect the terminal region of the long arm of chromosome 22 (the  paternal  chromosome in 75% of cases, [ citation needed ] ) from 22q13.3 to 22qter. Although the deletion is most typically a result of a de novo mutation, there is an inherited form resulting from familial  chromosomal translocations  involving the 22 chromosome. In the de novo form, the size of the terminal deletion is variable and can go from 130 Kb (130,000  base pairs ) to 9 Mb. Deletions smaller than 1 Mb are very rare (about 3%). The remaining 97% of terminal deletions impact about 30 to 190 genes (see list, below). At one time it was thought that deletion size was not related to the core clinical features. [ 17 ]  That observation lead to an emphasis on the  SHANK3  gene, which resides close to the terminal end of chromosome 22. Interest in  SHANK3  grew as it became associated with  autism spectrum disorder  (ASD) and  schizophrenia . [ 18 ]  Since then, twelve other genes on 22q13 ( MAPK8IP2 , [ 19 ]   CHKB , [ 20 ]   SCO2 , [ 21 ]   SBF1 , [ 22 ]   PLXNB2 , [ 23 ]   MAPK12 , [ 24 ]   PANX2 , [ 25 ]   BRD1 , [ 26 ]   CELSR1 , [ 27 ]   WNT7B , [ 28 ]   TCF20 [ 29 ] ) have been associated with autism spectrum disorder and/or schizophrenia (see references below). Some mutations of  SHANK3  mimic 22q13 deletion syndrome, but  SHANK3  mutations and microdeletions have quite variable impact. [ citation needed ]


Some of the core features of 22q13 deletion syndrome are dependent upon deletion size, and do not depend on the loss of  SHANK3 . [ 30 ] [ 31 ] [ 32 ]  As noted above, the distal 1 Mb of 22q is a gene rich region. There are too few clinical cases to statistically measure the relationship between deletion size and phenotype in this region.  SHANK3  is also adjacent to a gene cluster ( ARSA  and  MAPK8IP2 ) [ 33 ]  that has a high probability of contributing to ASD, [ 34 ]  suggesting the effects of  SHANK3  deletion may be indistinguishable from other genetic losses. A landmark study of  induced pluripotent stem cell  neurons cultured from patients with 22q13 deletion syndrome shows that restoration of the  SHANK3  protein produces a significant, but incomplete rescue of membrane receptors, supporting both a substantial role for  SHANK3  and an additional role for other genes in the distal 1 Mb of chromosome 22. [ 35 ]


There is an interest in the impact of  MAPK8IP2  (also called IB2) in 22q13 deletion syndrome. [ 36 ]  MAPK8IP2 is especially interesting because it regulates the balance between  NMDA receptors  and  AMPA receptors . [ 37 ]  The genes SULT4A1 [ 38 ]  and PARVB [ 39 ]  may cause 22q13 deletion syndrome in cases of more proximal interstitial and large terminal deletions. [ 32 ]  There are about 187 protein coding genes in the 22q13 region. [ 40 ]  A group of genes ( MPPED1 , [ 41 ]   CYB5R3 , [ 42 ]   FBLN1 , [ 43 ]   NUP50 , [ 44 ]   C22ORF9 , [ 45 ]   KIAA1644 , [ 46 ]   PARVB , [ 39 ]  TRMU, [ 47 ]   WNT7B [ 48 ]  and  ATXN10 [ 49 ] ), as well as  microRNAs  may all contribute to loss of language, a feature that varies notably with deletion size. [ 50 ]  The same study found that  macrocephaly  seen in 22q13 deletion syndrome patients may be associated with  WNT7B .  FBLN1  is responsible for synpolydactyly as well as its contribution to the neurological manifestations ( OMIM 608180 ).


Table of protein coding genes involved in 22q13 deletion syndrome (based on Human Genome Browser – hg38 assembly  [ 51 ] ). Underline identifies 13 genes that are associated with autism. [ 52 ] [ 53 ] [ 54 ] [ 55 ]  Bold identifies genes associated with hypotonia (based on Human Phenotype Browser  [ 56 ]  search for 'hypotonia' and the OMIM database  [ 57 ] ).


Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by  karyotype  analysis, but many terminal and interstitial deletions are too small to detect with this method. [ 8 ] [ 58 ]  Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. [ 59 ] [ 60 ]  Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole  exome sequencing  may replace  DNA microarray  technology for candidate gene evaluation. Biological parents should be tested with  fluorescence  in situ  hybridization  (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3). [ 61 ]


Clinical genetic evaluations and  dysmorphology  exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)


All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. [ 8 ]  All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.


Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination, and gait, as well as conditions that might be associated with hypotonia. [ 9 ]  Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities. [ 5 ]


All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. [ 62 ] [ 63 ]  Vesicouretral reflux, hydronephrosis, renal agenesis, dysplastic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.


Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and  patent ductus arteriosus . Cardiac evaluation, including echocardiography and electrocardiogram, should be considered. [ 8 ]


Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described. [ 64 ]


Table 3: Clinical Assessment Recommendations in Phelan–McDermid Syndrome


The true prevalence of PMS has not been determined. More than 1,200 people have been identified worldwide according to the Phelan–McDermid Syndrome Foundation. [ 65 ]  However, it is believed to be underdiagnosed due to inadequate genetic testing and lack of specific clinical features. It is known to occur with equal frequency in males and females. Studies using chromosomal microarray for diagnosis indicate that at least 0.5% of cases of ASD can be explained by mutations or deletions in the  SHANK3  gene. [ 58 ]  In addition, when ASD is associated with ID,  SHANK3  mutations or deletions have been found in up to 2% of individuals. [ 66 ] [ 67 ]


The first case of PMS was described in 1985 by Watt et al., who described a 14-year-old boy with severe intellectual disability, mild dysmorphic features and absent speech, which was associated with terminal loss of the distal arm of chromosome 22. [ 68 ]  In 1988, Phelan et al. described a similar clinical presentation associated with a  de novo  deletion in 22q13.3. Subsequent cases were described in the following years with a similar clinical presentation. Phelan et al. (2001), compared 37 subjects with 22q13 deletions with features of 24 cases described in the literature finding that the most common features were global developmental delay, absent or delayed speech and hypotonia. In 2001, Bonaglia et al., [ 69 ]  described a case that associated the 22q.13 deletion syndrome with a disruption of the  SHANK3  gene (also called  ProSAP2 ). The following year, Anderlid et al. (2002), [ 70 ]  refined the area in 22q13 presumably responsible for the common phenotypic presentation of the syndrome to a 100kb in 22q13.3. Out of the three genes affected,  SHANK3  was identified as the critical gene due to its expression pattern and function. Wilson et al. [ 71 ]  (2003) evaluated 56 patients with the clinical presentation of PMS, all of whom had a functional loss of one copy of the  SHANK3  gene. However, later the same group demonstrated that loss of  SHANK3  gene was not an essential requirement for the disorder. [ 72 ]


Aortic arch anomaly - peculiar facies - intellectual disability  is a rare,  genetic ,  congenital  developmental  anomaly  that is characterized by heart abnormalities, cranio-facial dysmorphia, and  intellectual disabilities . No new cases have been reported since 1968. [ 1 ] [ 2 ]


People with this disorder usually have the following symptoms: [ 3 ]


This disorder was first discovered in 1968, [ 4 ]  when a mother and 3 of her children (4 cases) were described with the symptoms mentioned above. In this case, additional features were found in a majority of the patients; three of the patients had esophageal indentation and left  ligamentum arteriosum , two of the patients, a still-born baby, had  anencephaly . Another child died due to  congenital heart disease . The child in question also had  microcephaly . [ 5 ]  This disorder is suspected to be autosomal dominant. [ 1 ]


DiGeorge syndrome , also known as  22q11.2 deletion syndrome , is a syndrome caused by a microdeletion on the long arm of  chromosome 22 . [ 7 ]  While the symptoms can vary, they often include  congenital heart problems , specific facial features, frequent infections,  developmental disability ,  intellectual disability  and  cleft palate . [ 7 ]  Associated conditions include  kidney problems ,  schizophrenia ,  hearing loss  and  autoimmune disorders  such as  rheumatoid arthritis  or  Graves' disease . [ 7 ] [ 8 ]


DiGeorge syndrome is typically due to the deletion of 30 to 40  genes  in the middle of  chromosome 22  at a  location  known as  22q11.2 . [ 3 ]  About 90% of cases occur due to a new  mutation  during early development, while 10% are  inherited . [ 7 ]  It is  autosomal dominant , meaning that only one affected chromosome is needed for the condition to occur. [ 7 ]  Diagnosis is suspected based on the symptoms and confirmed by  genetic testing . [ 5 ]


Although there is no cure, treatment can improve symptoms. [ 3 ]  This often includes a  multidisciplinary  approach with efforts to improve the function of the potentially many organ systems involved. [ 9 ]  Long-term outcomes depend on the symptoms present and the severity of the heart and immune system problems. [ 3 ]  With treatment, life expectancy may be normal. [ 10 ]


DiGeorge syndrome occurs in about 1 in 4,000 people. [ 7 ]  The syndrome was first described in 1968 by American physician  Angelo DiGeorge . [ 11 ] [ 12 ]  In late 1981, the underlying genetics were determined. [ 12 ]


The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure ( velopharyngeal insufficiency ),  learning disabilities , mild differences in facial features, and recurrent  infections .  Infections are common in children due to problems with the  immune system 's  T cell - mediated response  that in some patients is due to an absent or  hypoplastic   thymus . DiGeorge syndrome may be first spotted when an affected newborn has heart defects or convulsions from  hypocalcemia  due to malfunctioning  parathyroid glands  and low levels of parathyroid hormone ( parathormone ). [ citation needed ]


Affected individuals may also have other kinds of birth defects including kidney abnormalities and significant feeding difficulties as babies. Gastrointestinal issues are also very common in this patient population. Digestive motility issues may result in constipation. [ 13 ]  Disorders such as  hypothyroidism  and  hypoparathyroidism  or  thrombocytopenia  (low platelet levels), and  psychiatric  illnesses are common late-occurring features. [ 14 ]


Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of  schizophrenia . [ 15 ]  Studies provide various rates of 22q11.2DS in schizophrenia, ranging from 0.5 to 2.0% and averaging about 1.0%, compared with the overall estimated 0.025% risk of the 22q11.2DS in the general population. [ 16 ]


Salient features can be summarized using the mnemonic  CATCH-22  to describe 22q11.2DS, with the 22 signifying the chromosomal abnormality is found on the 22nd chromosome, as below: [ 17 ]


Individuals can have many possible features, ranging in number of associated features and from the mild to the very serious. Symptoms shown to be common include:


This syndrome is characterized by  incomplete penetrance . Therefore, there is a marked variability in clinical expression between the different patients. This often makes early diagnosis difficult. [ 19 ]


Children with DiGeorge syndrome have a specific profile in neuropsychological tests. They usually have a below-borderline normal IQ, with most individuals having higher scores in the verbal than the nonverbal domains. Some are able to attend mainstream  schools, while others are home-schooled or in special classes. The severity of hypocalcemia early in childhood is associated with autism-like behavioral difficulties. [ 20 ]


Adults with DiGeorge syndrome are a specifically high-risk group for developing schizophrenia. About 30% have at least one episode of  psychosis  and about a quarter develop  schizophrenia  by adulthood. [ 21 ]


Individuals with DiGeorge syndrome also have a higher risk of developing early onset  Parkinson's disease  (PD). Diagnosis of Parkinson's can be delayed by up to 10 years due to the use of  antipsychotics , which can cause parkinsonian symptoms. [ 22 ] [ 23 ]


Current research demonstrates a unique profile of speech and language impairments is associated with 22q11.2DS. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. [ contradictory ]  Common problems include hypernasality, language delays, and speech sound errors. [ 24 ] [ 25 ] [ 26 ]


Hypernasality  occurs when air escapes through the nose during the production of oral speech sounds, resulting in reduced  intelligibility . This is a common characteristic in the speech and language profile because 69% of children have  palatal  abnormalities. If the structure of the soft palate  velum  is such that it does not stop the flow of air from going up to the  nasal cavity , it will cause  hypernasal speech . This phenomenon is referred as  velopharyngeal inadequacy  (VPI). Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery. [ 24 ] [ 25 ] [ 27 ] [ 28 ] [ 29 ]


Difficulties acquiring vocabulary and formulating spoken language ( expressive language  deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion.  Vocabulary acquisition  is often severely delayed for preschool-age children. In some recent studies, children had a severely limited vocabulary or were still not verbal at 2–3 years of age. School-age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences.  Receptive language , which is the ability to comprehend, retain, or process spoken language, can also be impaired, although not usually with the same severity as expressive language impairments. [ 25 ] [ 28 ] [ 29 ] [ 30 ]