Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Genetic Complementation Test
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Amino Acid Sequence
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Polymorphism, Restriction Fragment Length
Sequence Analysis, DNA
Genetic Association Studies
Asian Continental Ancestry Group
Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.
European Continental Ancestry Group
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Tandem arrays of moderately repetitive, short (10-60 bases) DNA sequences which are found dispersed throughout the GENOME, at the ends of chromosomes (TELOMERES), and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit.
Because neither parent carries the tailless allele, a fully tailed Manx bred to another fully tailed Manx results in all fully ... The breed is said to be highly intelligent, playful, and in its behaviour reminiscent of dogs. For example, like some Maine ... Being homozygous for (having two copies of) the gene is usually lethal in utero, resulting in miscarriage. Thus, tailless cats ... give rise to a pattern of sometimes lethal health problems. The Pixie-bob breed also has a short tail, and may be genetically ...
It is highly gregarious on migration, travelling in large flocks that can contain hundreds or thousands of individuals. Huge ... About 500,000 years ago another rare recombination event of faeder and resident allele in the very same inverted region led to ... gene has severe deleterious effects and pedigree data of a captive ruff colony suggests that the inversion is homozygous lethal ... This highly gregarious sandpiper is migratory and sometimes forms huge flocks in its winter grounds, which include southern and ...
Natural selection can support lethal and harmful alleles, if their effects are felt after reproduction. The geneticist J. B. S ... This can prevent highly mutated cells from becoming cancerous. In culture, fibroblasts can reach a maximum of 50 cell divisions ... Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative ... Sub-lethal damage Transgenerational design Nelson, Paul; Masel, Joanna (5 December 2017). "Intercellular competition and the ...
Lethal white syndrome
... a highly conserved region of this protein among different species. Seven additional unrelated lethal white foal samples were ... "there are many overos that do not carry the lethal allele", which is technically correct, but only because the term "overo" ... Lethal white syndrome (LWS), also called overo lethal white syndrome (OLWS), lethal white overo (LWO), and overo lethal white ... The terms "piebald-lethal" and "spotting lethal" apply to similar conditions in mice and rats, respectively, both caused by ...
The most widely studied allele variants are the lethal yellow mutation (Ay) and the viable yellow mutation (Avy) which are ... This gene is highly similar to the mouse gene and encodes a secreted protein that may (1) affect the quality of hair ... Lethal yellow homozygotes are rare today, while lethal yellow and viable yellow heterozygotes (Ay/a and Avy/a) remain more ... The lethal yellow mutation (Ay) was the first embryonic mutation to be characterized in mice, as homozygous lethal yellow mice ...
Human mortality from H5N1
The highly lethal second and third waves of the 1918 Spanish flu evolved through time into a less virulent and more ... It is highly unlikely that all of the high-virulence alleles will simultaneously mutate and disappear if and when the ... This strain was "highly pathogenic" (deadly to birds) but caused neither illness nor death in humans. "The precursor of the ... NS codes for two nonstructural proteins (NS1 and NEP). The NS1 gene of the highly pathogenic avian H5N1 viruses circulating in ...
PDK1: Knockout is lethal; hypomorphic allele results in smaller organ volume and organism size but normal AKT activation. AKT: ... Translation of mRNA for IL1A is highly dependent upon mTOR activity. mTOR activity increases levels of IL1A, mediated by ... mTOR Complex 1 (mTORC1) is composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 ... Janssens V, Goris J (February 2001). "Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases ...
Maturity onset diabetes of the young
... normal allele which presumably functions normally. However, conditions involving people carrying two abnormal alleles have been ... or may be lethal for a fetus and not result in a viable child. The recognised forms of MODY are all due to ineffective insulin ... Their expression is transient but highly prevalent. The autoantibodies were found in patients with delayed diabetes onset, and ...
... of the individuals carry at least one of these lethal alleles, almost none carry two copies of the same lethal. Therefore, ... Therefore, predicting the actual evolution of fitness during inbreeding is highly elusive. However, the component of fitness ... However, for non-lethal deleterious alleles, the efficiency of purging would be smaller, and it can require larger populations ... As an example of genetic purging, consider a large population where there are recessive lethal alleles segregating at very low ...
GNAS complex locus
Many alleles in mice have been constructed for analyzing disease associations. Mice with this gene half knocked-out and half- ... This gene locus has a highly complex imprinted expression pattern. It gives rise to maternally-, paternally- and biallelically- ... some other alternations can be lethal. Metabolic problems resembling pseudohypoparathyroidism are seen in heterozygous mutated ... "Gnas Chemically induced Allele Detail MGI Mouse (MGI:2183318)". Mouse Genome Informatics. Retrieved 3 May 2019. "Nespas ...
Surfactant metabolism dysfunction
Mutated alleles are inherited in autosomal dominant fashion, although de novo mutations can also cause sporadic emergence of ... although the onset and severity of lung disease are highly variable, even within the same family. More than 40 ... any disruption to existence of SP-B results in ineffective respiration and lethal pulmonary conditions at birth. Pathology ... About 2/3 or 60%-70% of those accounted disease-causing alleles come from a frameshift mutation, called 121ins2, on exon 4 of ...
When the new allele is created, a heterozygote containing the newly created allele as well as the original will express the new ... Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from ... Kozmin S, Slezak G, Reynaud-Angelin A, Elie C, de Rycke Y, Boiteux S, Sage E (September 2005). "UVA radiation is highly ... When the allele has a complete loss of function (null allele), it is often called an amorph or amorphic mutation in the ...
The first Notch allele was established in 1917 by C.W. Metz and C.B. Bridges. In the late 1930s, studies of fly embryogenesis ... which is highly conserved in metazoans. The Notch extracellular domain (NECD) mediates interactions with DSL family ligands, ... was found to be a sex-linked dominant on the X chromosome that could only be observed in heterozygous females as it was lethal ... there are a set of highly conserved structures found in all Notch family proteins. The protein can broadly be split into the ...
... so that purging is weaker for non-lethal than for recessive lethal alleles. For very small populations, drift has a strong ... such as in the highly inbred population of Scandinavian wolves. This appears to be due to a selection pressure for more ... and has been demonstrated to occur rapidly where the recessive alleles have a lethal effect. The efficiency of purging will ... For alleles that confer an advantage in the heterozygous and/or homozygous-dominant state, the fitness of the homozygous- ...
... caused its lethal effects In the early placentae (6-8 weeks gestation), both parental H19 alleles (maternal and paternal) are ... The final product of the H19 gene is RNA H19 is highly expressed prenatally and downregulated postnatally Postnatally, H19 is ... The replication of two alleles of the same gene can differ according to which parent the allele originated from. On the human ... H19 is only transcribed from the maternally inherited allele; the paternal H19 allele is not expressed. H19 was first named ASM ...
Copperhead venom has an estimated lethal dose around 100 mg, and tests on mice show its potency is among the lowest of all pit ... It has also shown fondness for large insects and frogs, and though highly terrestrial, has been known to climb trees to gorge ... This process leads to genome-wide homozygosity, expression of deleterious recessive alleles, and often to developmental failure ...
"Mini-muscle" allele. A gene recently discovered in laboratory house mice, termed "mini-muscle", causes a 50% reduction in ... Gruneberg, H., 1938 An analysis of the "pleiotropic" effects of a new lethal mutation in the rat (Mus norvegicus). Proc. R. Soc ... "Highly expressed genes in yeast evolve slowly". Genetics. 158 (2): 927-931. PMC 1461684. PMID 11430355 ... A study on seed beetles found that intralocus sexual conflict arises when selection for certain alleles of a gene that are ...
1 allele from the mother and a *4 allele from the father, that individual would be an Intermediate Metabolizer (IM) (the ... TPMT is highly involved in 6-MP metabolism and TMPT activity and TPMT genotype is known to affect the risk of toxicity. ... A strong body of evidence suggests that patients affected by these genetic polymorphisms will experience severe/lethal ... This is a highly polymorphic enzyme with the variant CYP2B6*6 having special importance, as it leads to errors in RNA ...
The mini-muscle allele shows a mendelian recessive behavior. The mutation is a single nucleotide polymorphism (SNP) in an ... 2001). "Highly expressed genes in yeast evolve slowly". Genetics. 158 (2): 927-931. PMC 1461684. PMID 11430355. Camps, M.; et ... Gruneberg, H., 1938 An analysis of the "pleiotropic" effects of a new lethal mutation in the rat (Mus norvegicus). Proc. R. Soc ... A study on seed beetles found that intralocus sexual conflict arises when selection for certain alleles of a gene that are ...
... so that purging is weaker for non-lethal than for recessive lethal alleles. For very small populations, drift has a strong ... such as in the highly inbred population of Scandinavian wolves. This appears to be due to a selection pressure for more ... and has been demonstrated to occur rapidly where the recessive alleles have a lethal effect. The efficiency of purging will ... In this case, a is the recessive allele which has negative effects. In order for the a phenotype to become active, the gene ...
Violet budgerigar mutation
In the past, there was a view that the violet allele was lethal in double factor form, but this is now disproved with many ... In the UK the opinion of the highly respected budgerigar breeder, C H Rogers, writing in 1937, was that a true violet was first ... The Violet mutation has an incompletely dominant relationship to its wild-type allele. That is, there are three distinct ... Violet alleles, with the heterozygote having an intermediate appearance between the wild-type and the homozygote. Because the ...
Herpes simplex virus
The trial had a small sample of patients who did not have the antibody at baseline, so the results should be viewed as highly ... When HSV particles are exposed to doses of a DNA damaging agent that would be lethal in single infections, but are then allowed ... According to a study done in 1997, without the presence of the gene allele, HSV-1 does not appear to cause any neurological ... in people with the epsilon4 allele of the gene APOE. HSV-1 appears to be particularly damaging to the nervous system and ...
Epigenetics of human development
Airn is silenced in the maternal allele through Igf2r transcription. In the brain, however, Igf2r alleles are both expressed ... PRC2 is also highly associated with intergenic regions, subtelomeric regions, and long-terminal repeat transposons. PRC2 acts ... In most animals, especially mammals, uniparental inheritance of chromosomes is often lethal or results in developmental ... leading to Airn expression in the paternal allele, but not in the maternal allele. Airn acts by cis-acting silencing of the ...
Language, tools, lethal weapons, fire, cooking, etc., have a long-term effect on genetics. For example, cooking led to a ... Second, eusociality no longer seems to be confined to the hymenopterans; increasing numbers of highly social taxa have been ... Increased frequency or fixation of altruistic alleles can be accomplished through kin selection, in which individuals engage in ... Gene-culture coevolution allows humans to develop highly distinct adaptations to the local pressures and environments more ...
Mutations of synuclien alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... The role of autophagy in cancer is one that has been highly researched and reviewed. There is evidence that emphasizes the role ... In addition, full knockout of Beclin1 is embryonic lethal whereas knockout of Atg7 or Atg5 is not. ... Deregulation of the autophagy pathway and mutation of alleles regulating autophagy are believed to cause neurodegenerative ...
Medical genetics of Jews
... that could potentially cause disease and most people are heterozygotes for one or two recessive alleles that would be lethal in ... Ashkenazi Jews are also highly affected by other lysosomal storage diseases, particularly in the form of lipid storage ... This would be similar to the hemoglobin allele which is responsible for sickle-cell disease, but solely in people with two ... There is evidence that the population bottleneck may have allowed deleterious alleles to become more prevalent in the ...
The FLCN gene encodes a 64 kDa protein, FLCN, which is highly conserved across species. The majority of germline FLCN mutations ... Homozygous inactivation of Flcn in these animal models is lethal to the embryo. Tumors develop in mice injected with FLCN- ... in late-onset tumors that developed in aged Flcn heterozygous mice subsequent to loss of the remaining Flcn wild type allele, ... mTOR activation was seen in the highly cystic kidneys that developed in mice with kidney-targeted inactivation of Flcn. ...
Barker KT, Foulkes WD, Schwartz CE, Labadie C, Monsell F, Houlston RS, Harper J (July 2006). "Is the E133K allele of VG5Q ... It has been found that AGGF1 is highly expressed in some malignant tumours which has implicated AGGF1 in cancer. In vitro ... Depending on the mutation type, AGGF1 mutations can be lethal in either the heterozygous or homozygous genotype due to its ... Barker KT, Foulkes WD, Schwartz CE, Labadie C, Monsell F, Houlston RS, Harper J (July 2006). "Is the E133K allele of VG5Q ...
Drosophila hybrid sterility
Recent studies have shown that a critical gene for gender determination in Drosophila known as the sex-lethal gene is highly ... is if one sex chromosome of one species has recessive alleles interacting with autosomal alleles of the mating species. This ... The sex-lethal gene is often abnormally expressed in male hybrids from D. melanogaster mothers as a result of re-localization ... Another highly regarded figure in Drosophila research was Theodosius Dobzhansky, who invented the use of genetic markers and ...
Jack jumper ant
The LD50 (lethal dose) occurs at a lower concentration than for melittin, a peptide found in bee venom. Its LD50 value is 3.6 ... The ant has nine polymorphic loci, which yielded 67 alleles. The earliest known account of ant sting fatalities in Australia ... Allergy prevalence rates are significantly lower in highly urbanised areas and much higher in rural areas. These ants represent ... The jack jumper have been compared to other highly aggressive ant species, such as Brachyponera chinensis, Brachyponera ...
Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study. - PubMed - NCBI
Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this ... Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30-1·66; p=2·31 × 10-10) for rs1558375, 1·61 (1·38-1·89 ... study was to identify common genetic susceptibility alleles for gallbladder cancer.. METHODS: In this case-control genome-wide ...
Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus...
demonstrated that lethal EBOV infection is associated with loss and decreased activity of NK cells (11). In addition, Cimini et ... and they are encoded by a family of highly polymorphic genes located on human chromosome 19q13.4 within the leukocyte receptor ... González-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new ... lysine or asparagine for HLA-C alleles and threonine or isoleucine for HLA-B-Bw4 and HLA-A-Bw4 alleles (19). ...
Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus...
We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The ... demonstrated that lethal EBOV infection is associated with loss and decreased activity of NK cells (11). In addition, Cimini et ... and they are encoded by a family of highly polymorphic genes located on human chromosome 19q13.4 within the leukocyte receptor ... González-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new ...
Drosophila crinkled, Mutations of Which Disrupt Morphogenesis and Cause Lethality, Encodes Fly Myosin VIIA | Genetics
They were both lethal over severe ck alleles. The 14 cn bw recombinants could be either deletions extending proximally or ... C) Aristae on ck13/Df mutants (C′) are shorter and more highly branched than controls (C). Bar in C, for C and C′, 100 μm. ... Mutant alleles were mapped to ck by crossing to deletion stocks and by crossing ck alleles inter se. Adult flies prepared for ... would render both alleles equivalent in severity, yet they show different lethal phases. One possible explanation is that the ...
Drosophila Signal Peptide Peptidase Is an Essential Protease for Larval Development | Genetics
New alleles of Spp were generated by chemical mutagenesis. Five mutants were isolated that failed to complement the Df(2L)lwr14 ... All were larval lethal and no complementation was observed between any two mutants. We analyzed the three with the most severe ... These deletions remove the two final transmembrane helices containing the QPALLY region highly conserved throughout evolution ( ... These Spp alleles define a single complementation group. We identified two chromosomes with small deletions in the Spp gene. ...
Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamatergic synapse...
The Saccharomyces cerevisiae Hyperrecombination Mutanthpr1Δ Is Synthetically Lethal with Two Conditional Alleles of the Acetyl...
Structure and expression of the Saccharomyces cerevisiae CRY1 gene: a highly conserved ribosomal protein gene.Mol. Cell. Biol. ... The synthetic lethal interaction between hpr1Δ andacc1 is not allele specific.A temperature-sensitive allele of ACC1, mtr7, ... We have described a synthetic lethal interaction between a loss-of-function allele of HPR1 and two conditional alleles of ACC1 ... Several lines of evidence suggested that the synthetic lethal interaction of hpr1Δ with conditional acc1alleles was not simply ...
Mutations in the small subunit of the Drosophila U2AF splicing factor cause lethality and developmental defects | PNAS
Seasonal stress and inbreeding | Proceedings of the Royal Society of London B: Biological Sciences
During the inbreeding process lethal and some other highly deleterious alleles expressed under benign laboratory conditions ... The expression of lethal equivalents in different environments. (a) The average number of lethal equivalents (βavg) in each ... c) Lethal equivalents. For each inbred line, we calculated the number of lethal equivalents (β) under benign laboratory ... roughly equal across both field and laboratory environments since such alleles are likely to have similar lethal or near-lethal ...
Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer | JCB
bnch loss of function alleles are semi-lethal and disrupt a highly conserved predicted anion/sugar permease of the MFS. (A) The ... null allele (Sweeney and Davis, 2002) reveals that our bnch alleles are null, or at least strong loss-of-function alleles (Fig ... bnch is a semi-lethal locus encoding a highly conserved predicted sugar transporter of the major facilitator superfamily. We ... 1 C). Transheterozygous combinations of null alleles of bnch are pupal to pharate adult lethal. However, strongly dependent on ...
Stem Cell Epigenetics
KLF5 also has a proliferative role in cells and the loss of both KLF5 alleles is embryonic lethal.. ... In comparison to other live cell staining techniques, CDy1 is highly specific for pluripotent stem cells and unlike live ... KLF5 (along with KLF2 and KLF4) is highly expressed in undifferentiated mouse embryonic stem cells and downregulated during ...
The other two crol alleles display lethal phenotypes that are indistinguishable from those seen in crol 4418 mutants. The ... While the penetrance of the microcephalic phenotype is variable, the crooked legs phenotype is highly penetrant and is ... Three P-element-induced pupal lethal mutations were identified that define a single lethal complementation group: l(2)04418, l( ... An identical lethal phase can be seen in animals that carry crol 4418 in combination with Df(2L)esc 10, a 380 kb deficiency ...
Extracellular leucine-rich repeat proteins are required to organize the apical extracellular matrix and maintain epithelial...
Alleles used were: I: mec-8(u218) (Chalfie and Au, 1989). X: let-4(mn105) (Meneely and Herman, 1979), unc-3(e151) (Hodgkin, ... Embryonic lethal phenotype varied. Most mec-8; let-4(RNAi) embryos swelled. egg-6(RNAi) embryos arrested at ∼40 cell stage. (B ... let-4(mn105) is a recessive, loss-of-function mutation and caused highly, but not completely, penetrant lethality (Fig. 2A). ... Strains and alleles. Strains were grown at 20°C and maintained under standard conditions (Brenner, 1974) unless otherwise noted ...
polo, a mitotic mutant of Drosophila displaying abnormal spindle poles | Journal of Cell Science
One allele is a larval lethal, whereas another is semi-lethal with about 7% of homozygotes surviving as adults. Embryos from ... homozygous polo females have aberrant mitotic spindles that are highly branched and have broad poles. Immunofluorescence ... Neuroblast cells in larvae homozygous for mutant alleles of the locus polo show a high frequency of metaphases in which the ...
Transcription-Associated Mutation in Bacillus subtilis Cells under Stress
... stochastic processes acting upon derepressed genes could bias the accumulation of mutations to highly transcribed alleles. ... mutations enhancing cell survival while a transcription-associated mutation bias would aid the population in avoiding a lethal ... For this assay, we used a derivative of YB955 that contains two identical defective leuC alleles: one allele located within the ... Fig.1A)1A) (41). In addition to the leuC427 allele placed at the ilv-leu locus (44), a copy of leuC427 was placed under the ...
Loss of the Major GABAA Receptor Subtype in the Brain Is Not Lethal in Mice | Journal of Neuroscience
c,g, Targeted allele after homologous recombination for α1 and for β2 allele, and after cre-mediated removal of the neomycin ... Correctly targeted ES cell clones were injected into C57BL6 blastocysts, and one of three clones gave rise to highly chimeric ... a, b, e,f, Schematic representation of the WT α1 (a, b) and β2 allele (e, f) of the GABAA receptor and the corresponding ... Loss of the Major GABAA Receptor Subtype in the Brain Is Not Lethal in Mice. Cyrille Sur, Keith A. Wafford, David S. Reynolds, ...
The Pleiotropic Two-Component Regulatory System PhoP-PhoQ | Journal of Bacteriology
Salmonella strains harboring null alleles of the phoP or phoQ gene are highly attenuated for virulence: their median lethal ... One of the paradoxical virulence phenotypes associated with PhoP-PhoQ is that displayed by a strain harboring the pho-24allele ... Salmonella phoP mutants are highly susceptible to a variety of antimicrobial peptides, including the mammalian defensins, the ... a Yersinia phoPmutant has a mean lethal dose that is 75-fold higher than that of the isogenic wild-type strain (65). Even ...
For the analysis of the accumulated load of allele loss, fractional allele loss (FAL) was calculated for each sample. The ... It has been shown that the process of cancer metastasis is a highly inefficient one. This concept has recently been ... individual cells are required to survive a series of potentially lethal tumor host interactions to successfully form viable and ... the maximal fractional allele loss value; FALmin, the minimal fractional allele loss value; MSI, microsatellite instability; AD ...
JoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols
In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian ... To address this need, we have developed a pooled sequencing approach1,9 and a novel software package1 for highly accurate rare ... whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. This newly identified lethal has ... allele 1: allele 2) calculation. The allelic ratio obtained for cDNA is normalized using that measured from genomic DNA, where ...
This dominant conditional lethal allele was named Killer-of-prune (K-pn) and turned out to be a missense mutant allele of awd. ... Sturtevant, A. (1956). A highly specific complementary lethal system in Drosophila melanogaster. Genetics 41: 118-123. PubMed ... The highly restricted expression patterns of the Drosophila alpha-Adaptin and the specific defects in aAdaptin mutants exclude ... ECR-B1 is highly expressed and/or required for pruning in remodeling neurons of the CNS. MB γ neurons and antennal lobe ...
Loss of the plant DEAD-box protein ISE1 leads to defective mitochondria and increased cell-to-cell transport via plasmodesmata ...
Two additional mutant alleles, ise1-2 and ise1-3, were identified originally as Agrobacterium-mediated T-DNA insertions in ... ISE1 (At1g12770) encodes a highly conserved 441-aa DEAD-box RNA helicase domain and a unique 110-aa N-terminal domain. ISE1 was ... We identified an Arabidopsis thaliana embryo lethal mutant increased size exclusion limit 1 (ise1) that results in increased PD ... 2B). The missense mutation in the ise1-1 allele substitutes glutamic acid for the first glycine of the conserved "GG loop" of ...
RAS, wanted dead or alive: Advances in targeting RAS mutant cancers | Science Signaling
... all MT RAS-driven cells exhibit the same oncogene dependencies and that synthetic lethal interactions with MT RAS are highly ... KRAS Alleles: The devil is in the detail. Trends Cancer 3, 686-697 (2017).. ... RAS synthetic lethal screens revisited: Still seeking the elusive prize? Clin. Cancer Res. 21, 1802-1809 (2015).. ... A systems mechanism for KRAS mutant allele-specific responses to targeted therapy. Sci. Signal. 12, eaaw8288 (2019).. ...
Use of a Sibling Subtraction Method for Identifying Causal Mutations in Caenorhabditis elegans by Whole-Genome Sequencing | G3:...
This study also highlights the utility of using synthetically lethal combinations of weak aphenotypic alleles as a genetic ... make the identification of weak alleles and combinatorial-dependent phenotypes highly feasible. Finally, because SSM/WGS is not ... Our studies also underscore the utility of using weak alleles in synthetic-lethal combinations as starting strains for ... two new alleles of F56D12.6 (fd211, 13 bp deletion; fd212, 10 bp deletion), and three new alleles of B0302.1 (fd213, 16 bp ...
A systematic survey to identify lethal recessive variation in highly managed pig populations | BMC Genomics | Full Text
Our study shows that although lethal recessive variation is present, the frequency of these alleles is invariably low in these ... Until recently, the presence of recessive embryonic lethal variation could only be measured indirectly through reduced ... Lethal recessive variation can cause prenatal death of homozygous offspring. Although usually present at low-frequency in ... highly managed populations. Nevertheless, due to cumulative effects of deleterious variants, large numbers of affected ...
The conserved P body component HPat/Pat1 negatively regulates synaptic terminal growth at the larval Drosophila neuromuscular...
hpatd3 was not lethal in trans to a recessive lethal allele of the nearest gene, CG3995 (CG3995LL03178; no alleles are ... P bodies are highly conserved cytoplasmic RNPs linked to both mRNA decay and translational repression pathways. In the former, ... Most alleles of hpat (also known as patr-1 or protein associated with topo II related-1) were recessive lethal and homozygous ... 7B). Two lethal alleles of dcp2 were examined: dcp2BG01766 and dcp2GS3219. Only dcp2BG01766 homozygous mutants resulted in ...
Frequencies of Certain Complement Protein Alleles and Serum Levels of Anti-Heat-Shock Protein Antibodies in Cerebrovascular...
Previously we have found a highly significant association between the morbidity and mortality of myocardial infarction and C4B* ... in C4B*Q0 carriers myocardial infarction had a significantly higher risk for lethal outcome compared with noncarriers.9 ... In CVD patients the frequency of the C4A*2 allele was relatively low, while that of the C4A*4 allele was relatively high. ... Q0, the silent allele of 1 of the 2 genes encoding C4, a component of the complement system.9 The C4B*Q0 allele was found with ...
Manx cat - Wikipedia
Because neither parent carries the tailless allele, a fully tailed Manx bred to another fully tailed Manx results in all fully ... The breed is said to be highly intelligent, playful, and in its behaviour reminiscent of dogs. For example, like some Maine ... Being homozygous for (having two copies of) the gene is usually lethal in utero, resulting in miscarriage. Thus, tailless cats ... give rise to a pattern of sometimes lethal health problems. The Pixie-bob breed also has a short tail, and may be genetically ...
Dsc Orthologs Are Required for Hypoxia Adaptation, Triazole Drug Responses, and Fungal Virulence in Aspergillus fumigatus |...
2A and B). For each of the dsc mutants, ectopic reconstitution of the wild-type allele restored antifungal drug responses to ... SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. Here we ... 3A). Despite a moderate amount of growth under hypoxia, theΔdscC strain was also highly attenuated in virulence (P , 0.001) ( ... 3B). Reconstitution of the respective wild-type alleles in ΔdscA and ΔdscC strains restored virulence comparable to that of the ...
ERC FUNDED PROJECTS | ERC: European Research Council
... use allele engineering as a curative therapy of scurfy syndrome, a lethal monogenic autoimmune disease. Allele engineering ... The new method will not only provide a greater number of highly accurate prenatal diagnoses of genetic disorders, but will do ... use allele engineering as a curative therapy of scurfy syndrome, a lethal monogenic autoimmune disease. Allele engineering ... We have developed "allele engineering", a new technology that solves this challenge. Here, we outline how allele engineering ...
Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome
DeleteriousPhenotypeEmbryonicMutant alleleGeneMutationsGenesMutationPhenotypesEmbryo lethalConditional AllelesHeterozygousMutantsPenetrantDrosophilaRisk allelesAbnormalLethalityMiceDevelopmentalSynthetic lethalStrainsSevereDiploid GenomeSynthetically lethalProteinIsolatesSomaticArabidopsisEncodesGenotypePutativeSusceptibilityMitoticWeakVivoCause lethalLocusTumorsMRNANullHomozygotesChromosomeProteinsSuppressDisordersSubtypeWild-typeStrain
- Stressors, such as extreme temperatures, pathogens and exposure to chemicals, are predicted to amplify the fitness costs associated with inbreeding (i.e. inbreeding depression) by altering the expression of deleterious alleles (genetic load) in homozygous individuals [ 5 , 9 ], which in turn can heighten extinction risk for small populations [ 8 , 10 ]. (royalsocietypublishing.org)
- With the mutation identified, selection against the deleterious allele in breeding schemes will aid in reducing the incidence of this defect in the population. (jove.com)
- Whole-genome resequencing proved to be a powerful strategy to rapidly identify a previously mapped deleterious mutation in a known carrier of a recessive lethal allele. (jove.com)
- The cause of inbreeding depression is the accumulation of (recessive) deleterious alleles increasing in frequency and becoming expressed in homozygous state due to drift in small populations [ 1 ]. (biomedcentral.com)
- The inefficiency of purging deleterious variation, even from highly managed populations, is particularly apparent if there is an unpredictable, or poorly characterized relationship between genotype and phenotype. (biomedcentral.com)
- Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits. (harvard.edu)
- Using ENU, we gathered a collection of 13 temperature-sensitive mutants and 80 auxotrophic mutants including two deleterious alleles of the human ortholog ATIC. (g3journal.org)
- Previous CHI screening between actin and null alleles for non-essential genes uncovered ∼240 deleterious CHI interactions. (prolekare.cz)
- Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. (asm.org)
- While these and other recessive lethal and deleterious alleles are likely to accumulate in C. albicans due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the C. albicans species. (asm.org)
- Using a combination of an I-SceI meganuclease-mediated DNA DSB, a fluorescence-activated cell sorter (FACS)-optimized reporter of LOH, and a compendium of 155 genome sequences, we were able to unmask and identify recessive lethal and deleterious alleles in isolates of Candida albicans , a diploid yeast and the major fungal pathogen of humans. (asm.org)
- The synthetic lethal phenotype of the acc1 cs hpr1 Δ double mutant was only partially complemented by exogenous fatty acids. (asm.org)
- In this way, we rescued the lethal phenotype imparted by lin-26 null mutations and uncovered a highly penetrant sterile phenotype. (biologists.org)
- A "paramutagenic" allele in heterozygotes transmits the phenotype of the heterozygotes to the wild-type allele ("paramutant") in a stable manner through generations. (plos.org)
- SRm160 is required for normal somatic sex determination, since its alleles strongly enhance a subtle sex transformation phenotype induced by Doa kinase alleles. (cnrs.fr)
- In the Columbia (Col) accession, a rpt5a mutant allele did not display such a phenotype because the RPT5b Col allele complements the rpt5a defect in the male gametophyte, whereas the RPT5b Ws allele does not. (mybiosource.com)
- Double rpt5a rpt5b mutants in Col background showed a complete male and female gametophyte lethal phenotype. (mybiosource.com)
- Another mor1 allele, rid5 , has a similar morphological phenotype to the mor1 mutants. (plantphysiol.org)
- In contrast, mice homozygous for a Gcn5 Δex3-18 allele created by Cre-loxP mediated deletion display a phenotype identical to our original Gcn5 null mice. (tmc.edu)
- Strikingly, a Gcn5flox(neo) allele, which contain a neomycin cassette in the second intron of Gcn5 is only partially functional and gives rise to a hypomorphic phenotype. (tmc.edu)
- Here, we report that the nonneurovirulent strain equid herpesvirus type 1 strain NY03 caused lethal neurological disease in horses after mutation of A(2254) G(2254) (N-752 D-752), thereby providing final proof that the D-752 allele in the viral DNA polymerase is necessary and sufficient for expression of the lethal neurovirulent phenotype in the natural host. (ugent.be)
- The lmgA ORF alone was sufficient to rescue the lethal and mitotic phenotypes of the lmg(138) null allele and to complement the temperature sensitive lethal phenotype of the APC11-myc9 budding yeast mutant. (lancs.ac.uk)
- This study provides a first example of a dominant COL2A1 splice site variant as candidate causal mutation of a severe lethal chondrodysplasia phenotype. (biomedcentral.com)
- This lethal phenotype was rescued through transgenic expression of human wild type as well as mutant (hFXN(G130V) and hFXN(I154F)) frataxin. (inserm.fr)
- We have systematically screened EMS-mutagenized Drosophila for embryonic lethal strains with defects in glutamatergic synaptic transmission. (nih.gov)
- KLF5 (along with KLF2 and KLF4) is highly expressed in undifferentiated mouse embryonic stem cells and downregulated during early stages of differentiation. (activemotif.com)
- KLF5 also has a proliferative role in cells and the loss of both KLF5 alleles is embryonic lethal. (activemotif.com)
- Until recently, the presence of recessive embryonic lethal variation could only be measured indirectly through reduced fertility. (biomedcentral.com)
- Previous studies in our lab using a constitutive null allele demonstrated that Gcn5 knock out mice are embryonic lethal, precluding the study of Gcn5 functions at later developmental stages. (tmc.edu)
- Importantly, none of these helicases could functionally compensate for Mov10, since the Mov10 knockout is embryonic lethal in the mouse. (biomedcentral.com)
- We also validated our predictions for other mouse mutagenesis methodologies, demonstrating that the predictions are accurate for lethal phenotypes isolated in random chemical mutagenesis screens and embryonic stem cell screens. (biologists.org)
- Embryonic lethal mutations (a total of 37) were overwhelmingly the largest class of mutants recovered. (searlescholars.net)
- No homozygous recessive individuals were found in 749 genotyped animals, whereas all known carriers and carrier haplotypes possessed one copy of the mutant allele. (jove.com)
- 1. You must have no Wild type allele and two mutated alleles (either same mutation of compound heterozygote), or hemizygotes -mutant allele for AR disorders are rare, affect the function of enzymes and reduce or eliminate function of the gene product. (brainscape.com)
- What is the chance she would then donate the mutant allele? (brainscape.com)
- All five available cases carried the mutant allele in heterozygous state and all five dams were homozygous wild type. (biomedcentral.com)
- The sire VH Cadiz Captivo was shown to be a gonadal and somatic mosaic as assessed by the presence of the mutant allele at levels of about 5 % in peripheral blood and 15 % in semen. (biomedcentral.com)
- In a screen for mutants that display synthetic lethal interaction with hpr1 Δ, a hyperrecombination mutant of Saccharomyces cerevisiae , we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1 cs , encoding the rate-limiting enzyme of fatty acid synthesis. (asm.org)
- This screen yielded a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1-200 cs , hereafter referred to as acc1 cs ( 14 ). (asm.org)
- Type I IFN and type III IFN trigger highly similar gene expression profiles in responsive cells, suggesting that both IFN types might serve similar functions. (asm.org)
- Defective alleles of this gene cause AICA-ribosiduria, a severe genetic disease. (g3journal.org)
- Compound heterozygous is that both alleles are mutated but the mutations are found in different parts of the gene. (brainscape.com)
- A mutation in the middle of the endothelin receptor type B (EDNRB) gene causes lethal white syndrome when homozygous. (wikipedia.org)
- A mutation in the middle of the EDNRB gene, Ile118Lys, causes lethal white syndrome. (wikipedia.org)
- The insert is a PZ element located 680 bp upstream from the ATG of the Delta ( Dl ) gene, encoding the Notch ligand involved in wing vein development, and acts as a null allele. (plos.org)
- In vivo CRISPR/Cas9-mediated gene editing is a promising strategy that could be used to eliminate the disease-causing Ryr2 allele and hence rescue catecholaminergic polymorphic ventricular tachycardia. (nih.gov)
- Thus, T.g.HSP70 gene vaccine induced protective immunity against T.g.HSP70-induced PAF-mediated lethal anaphylactic reaction in T. gondii-infected mice. (blogspot.com)
- The symptoms are highly variable in their clinical expression, and relate to numerous mutations in this gene. (biomedcentral.com)
- The disease is highly variable in its clinical expression, due to strong allelic heterogeneity in the ALPL gene. (biomedcentral.com)
- Loss of Securin reduces Separase activity because deletion of just one copy of the Separase gene is lethal to embryos lacking Securin. (ox.ac.uk)
- Epidemiological studies have shown that a single-nucleotide polymorphism in the equid herpesvirus type 1 DNA polymerase gene is associated with outbreaks of highly lethal neurological disease in horses. (ugent.be)
- C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4 . (rupress.org)
- Mining of genome sequencing data for 155 C. albicans isolates allowed the identification of a recessive lethal allele in the GPI16 gene on Chr4B unique to C. albicans strain SC5314 which is responsible for this inviability. (asm.org)
- These noncoding, low-penetrance, cancer-susceptibility alleles likely contribute to quantitative changes in gene expression and, as such, are difficult to find. (aacrjournals.org)
- Results: The lmg gene was initially identified through a pharate adult lethal P element insertion mutation expressing developmental abnormalities and widespread apoptosis in larval imaginal discs and pupal abdominal histoblasts. (lancs.ac.uk)
- Familial retinoblastoma is a highly penetrant genetic disease that usually develops by carrying germline mutations that inactivate one allele of the RB1 gene, leading to multiple retinoblastomas. (sigmaaldrich.com)
- using a partial loss of function allele, we reveal a role for this gene in tissue specific transcription. (prolekarniky.cz)
- In 2007, two independent mutations affecting the coding region of the aggrecan ( ACAN ) gene causing lethal chondrodysplasia in Dexter cattle (OMIA 001271-9913) were described. (biomedcentral.com)
- Therefore, in this study, we performed a cross-species gene expression study of the peripheral blood from human patients and from the highly genetically diverse Collaborative Cross (CC) mouse population after IV infection. (openrepository.com)
- Our results demonstrate that changes of gene expression in individual genes are highly similar in mice and humans. (openrepository.com)
- We conclude that the mouse is a highly valuable in vivo model system to validate and to discover gene candidates which can be used as biomarkers in humans. (openrepository.com)
- The other mutation is in a hypomorphic allele of the DNA replication licensing gene Mcm4, causing a dramatic elevation in chromosome instability. (searlescholars.net)
- These observations suggest that the basis for the synthetic lethal interaction between hpr1 Δ and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A) + RNA production and export that results in an altered structure of the nucleolus. (asm.org)
- Surprisingly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. (nih.gov)
- The acquisition of mutations was directly correlated to the level of transcription of a defective leuC allele placed under selection. (pubmedcentralcanada.ca)
- While cells are under stressful conditions, stochastic processes acting upon derepressed genes could bias the accumulation of mutations to highly transcribed alleles. (pubmedcentralcanada.ca)
- Selection would favor mutations enhancing cell survival while a transcription-associated mutation bias would aid the population in avoiding a lethal genetic load. (pubmedcentralcanada.ca)
- In support of this idea, several studies on adaptive mutagenesis have noted the appearance of mutations principally in chromosomal alleles under selection ( 17 , 40 ). (pubmedcentralcanada.ca)
- Importantly, this has the potential to create the entire spectrum of human-disease relevant mutations, including null, hypomorphic, and gain-of-function alleles. (biomedcentral.com)
- Also interesting is that there are dominant inherited disorders which are highly lethal and X- or Y-linked disorders related to mutations in genes located on our sex-determining chromosomes. (sciencenewsarticles.org)
- SRm160 mutations are recessive lethal, while its overexpression generates phenotypes including roughened eyes and highly disorganized internal eye structure, which are due at least in part to aberrantly high levels of apoptosis. (cnrs.fr)
- we identified several lethal mutations in AMPKα . (biologists.org)
- Drosophila lethal-Abruptex is a similar condition because it is also caused only by mutations that increase or decrease the number of cysteines within the EGF repeat portion of the Notch protein. (ahajournals.org)
- A fourth synthetic lethal interaction has been found between hpr1 Δ and a mutant carrying a deletion of one copy of the histone H3-H4 genes ( 10 ). (asm.org)
- The three human RAS genes encode four highly identical proteins (83 to 85% identity): HRAS, NRAS, and KRAS4A and KRAS4B, with KRAS encoding splice variants due to alternative exon 4 utilization. (sciencemag.org)
- Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. (ahajournals.org)
- Previously we have found a highly significant association between the morbidity and mortality of myocardial infarction and C4B*Q0, the silent allele of 1 of the 2 genes encoding C4, a component of the complement system. (ahajournals.org)
- Además, hemos demostrado que respuestas asociadas a PTI, como el aumento en la concentración de calcio citoplásmico, la producción de especies reactivas de oxígeno, la fosforilación de MAP quinasas y la expresión de genes de defensa, no están afectadas en el mutante yda11. (upm.es)
- In Arabidopsis, the RPT5 subunit is encoded by two highly homologous genes, RPT5a and RPT5b. (mybiosource.com)
- In this report, we have extended CHI screening to null alleles for essential genes by mating a query strain to sporulations of heterozygous knock-out strains. (prolekare.cz)
- Thus, genes located in the chromosome 10 region and highly expressed in the hippocampus are potential candidates. (gnxp.com)
- We have created conditional knockout alleles of the mouse Separase and Securin genes. (ox.ac.uk)
- A recent explosion of genome-wide association studies (GWAS) has identified several putative cancer-associated risk alleles, many of which are located near known cancer genes, although not within classic exonic boundaries (reviewed in ref. 2 ). (aacrjournals.org)
- To further examine the correlation between transcription and adaptive mutation, we placed a point-mutated allele, leuC427 , under the control of an inducible promoter and assayed the level of reversion to leucine prototrophy under conditions of leucine starvation. (pubmedcentralcanada.ca)
- RAD50 mutation impaired activation of ataxia telangiectasia mutated (ATM) signaling, leading to a synthetic lethal effect when checkpoint inhibition was combined with DNA-damaging chemotherapy. (aacrjournals.org)
- The mutation is visible lethal. (ias.ac.in)
- The phenotypic and genetic findings are comparable to a previously reported COL2A1 missense mutation underlying lethal chondrodysplasia in the offspring of a mosaic French Holstein sire (Igale Masc). (biomedcentral.com)
- Often spoken of as the ABO blood group, these three alleles, A, B, and O, can yield a possible four phenotypes and six different genotypes. (sciencenewsarticles.org)
- Moreover, modification of SRm160 by DOA kinase appears to be necessary for its activity, since Doa alleles suppress phenotypes induced by SRm160 overexpression in the eye and enhance those in genital discs. (cnrs.fr)
- So-called conditional alleles are frequently generated by individual amino acid substitutions, which may alter post-translational modification sites, unwind binding motives, impair the active center, etc. without affecting the overall polypeptide structure. (g3journal.org)
- Carriers, which are heterozygous-that is, have one copy of the mutated allele, but themselves are healthy-can now be reliably identified with a DNA test. (wikipedia.org)
- Complex heterozygous interactions are potentially important to human genetic disease as loss-of-function alleles are common in human genomes. (prolekare.cz)
- To better understand the in vivo function of Hpr1p, a screen was initiated to isolate additional mutants that exhibit synthetic lethal interaction with hpr1 Δ. (asm.org)
- Double mutants of weak CLPR1 and 2 alleles were seedling lethal, showing that a minimum concentration of different ClpR proteins is essential for Clp function. (plantcell.org)
- Consistent with a general role in splicing, a null allele of dU2AF38 is fully penetrant recessive lethal, like null alleles of the Drosophila U2AF large subunit. (pnas.org)
- Combining weak aphenotypic alleles of nekl-2 and nekl-3 leads to penetrant molting defects and larval arrest. (g3journal.org)
- Specifically, the strongest of these new alleles was characterized by the absence of lin-26 expression in the somatic gonad, the presence of endomitotic oocytes, decreased germline proliferation, a protruding vulva and a less penetrant absence of gonad arms. (biologists.org)
- Furthermore, these data, collected under natural field conditions, conformed to the same predictive linear relationship seen in Drosophila laboratory studies, with inbreeding depression increasing by 0.17 lethal equivalents for every 10 per cent increase in stress level. (royalsocietypublishing.org)
- Although its biochemical functions have been extensively described, its genetic interactions and potential participation in signaling pathways remain largely unknown, despite the fact that it is highly phosphorylated in both mammalian cells and Drosophila. (cnrs.fr)
- Summary of Comment - Drosophila lethal-Abruptex and human CADASIL are precisely analogous at the molecular level, and both are genetically dominant. (ahajournals.org)
- Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. (gnxp.com)
- The embryos in the abnormal seeds are predominantly homozygous for the disruption allele. (plantphysiol.org)
- Further investigations are carried out to explain the genetic determination of abnormal PRNP octa-peptide repeat allele segregation, which suggests possible lethal cis-trans linkage effects. (psu.edu)
- hpr1 Δ was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1 , mtr7 (mRNA transport), indicating that the lethality of the acc1 cs hpr1 Δ double mutant was not allele specific. (asm.org)
- Amorphic alleles show late lethality and greater frequencies of hyperploid mitotic cells. (rupress.org)
- In Wassilewskija (Ws) accession: mutant alleles of RPT5a displayed 50% pollen lethality, indicating that RPT5a is essential for male gametophyte development. (mybiosource.com)
- The creation of a conditional Gcn5 null allele, Gcn5flox allele, bypasses the early lethality. (tmc.edu)
- Guide RNAs were designed to specifically disrupt the R176Q allele in the R176Q/+ mice using the SaCas9 ( Staphylococcus aureus Cas9) genome editing system. (nih.gov)
- Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) was proven to induce lethal anaphylactic reaction in T. gondii-infected mice through platelet-activating factor (PAF)-mediated, but not classical IgE-dependent, pathway via TLR4/MyD88 signal pathway. (blogspot.com)
- Two isolates lethal to marsupials, were avirulent to mice. (blogspot.com)
- Mice homozygous for this allele are viable and appear healthy. (tmc.edu)
- Both C3H/HeJ and C57BL/10ScCr mice are homozygous for a mutant Lps allele ( Lps d/d ) that confers hyporesponsiveness to LPS challenge, and therefore exhibit natural tolerance to its lethal effects. (rupress.org)
- Remarkably, these mutant mice are highly susceptible to mammary adenocarcinomas. (searlescholars.net)
- However, the functions of these kinases in cell division throughout development has been revealed through the study of series of mutant alleles that show developmental arrest at different stages. (rupress.org)
- Our findings also point to another synthetic lethal target in tumors with inactivated RB1 and highlight the importance of collateral damage in carcinogenesis. (sigmaaldrich.com)
- A major reason for this interest is that fungal strains with a deficient ability to adapt to hypoxia fail to cause lethal disease in murine models. (asm.org)
- APEC strains of high virulence are lethal for 1-day-old chicks when administered subcutaneously. (asm.org)
- Still, staph itself isn't considered a priority pathogen, despite the emergence of highly resistant and increasingly virulent strains. (rapeutation.com)
- Severe ck alleles, likely to be molecular nulls, die as embryos or larvae, but all allelic combinations tested thus far yield a small fraction of adult "escapers" that are weak and infertile. (genetics.org)
- Understanding the function of MOR1 therefore relies on the identification of weak alleles or ones that generate severe defects only under specific conditions. (plantphysiol.org)
- The most severe forms are found in lethal congenital generalized chondrodysplasia, which was originally reported in Dexter cattle in 1904 [ 1 ] and usually referred to as "bulldog calves. (biomedcentral.com)
- The diploid genome of the yeast Candida albicans is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH) events. (asm.org)
- We show that a pool of green fluorescent protein-tagged Sec13p localizes to the nuclear pores in vivo, and identify sec13 mutant alleles that are synthetically lethal with nup85Δ and affect the localization of a green fluorescent protein-Nup49p reporter protein. (rupress.org)
- The dU2AF38 protein is highly homologous to hU2AF35 containing a conserved central arginine- and serine-rich (RS) domain. (pnas.org)
- AMP-activated protein kinase (AMPK) is an evolutionarily highly conserved key metabolic sensor of the cell. (jneurosci.org)
- However, some variant alleles produce alternative transcripts that encode (partially) functional protein isoforms leading to possible incorrect risk estimations. (nature.com)
- The temperature-sensitive mor1-1 , mor1-2 , and rid5 alleles are clearly valuable tools for understanding the function of the wild-type protein. (plantphysiol.org)
- Our results demonstrate that recessive lethal alleles in the genomes of C. albicans isolates prevent the occurrence of specific extended LOH events. (asm.org)
- To determine if lin-26 functions in the somatic gonad, we have generated gonad-specific lin-26 alleles obtained by integration of lin-26 promoter deletion derivatives into a lin-26 null mutant background. (biologists.org)
- This work highlights the potential of somatic genome editing approaches for the treatment of lethal autosomal-dominant inherited cardiac disorders, such as catecholaminergic polymorphic ventricular tachycardia. (nih.gov)
- Esta Tesis describe la caracterización funcional de la MAP quinasa quinasa quinasa (MAP3K) YODA (YDA), que actúa como un regulador clave de la PTI en Arabidopsis. (upm.es)
- Nuestros datos indican que esta función es independiente de las respuestas inmunes mediadas por los receptores previamente caracterizados FLS2 y CERK1, que reconocen los PAMPs flg22 y quitina, respectivamente, y que están implicados en la resistencia de Arabidopsis frente a bacterias y hongos. (upm.es)
- La expresión constitutiva de la proteína CA-YDA en plantas de Arabidopsis no provoca un aumento de las respuestas PTI, lo que sugiere la existencia de mecanismos de resistencia adicionales regulados por YDA que son diferentes de los regulados por FLS2 y CERK1. (upm.es)
- The α subunit (AMPKα) encodes for a highly conserved serine/threonine kinase, whereas the other subunits are regulatory. (biologists.org)
- So, if we say the trait for dimpled chin is represented by a lowercase letter d, then an individual who inherits two recessive alleles, one that came from each parent, will have the dd genotype. (sciencenewsarticles.org)
- Then what if a person inherits one dominant allele and one recessive allele - the genotype of Dd? (sciencenewsarticles.org)
- In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. (biomedcentral.com)
- This search led to the discovery of a putative recessive lethal in Jersey cattle on Bos taurus autosome 15. (jove.com)
- The haplotype, denoted JH1, was associated with reduced fertility, and further investigation identified one highly-influential Jersey bull as the putative source ancestor. (jove.com)
- No detectable off-target mutagenesis was observed in the wild-type Ryr2 allele or the predicted putative off-target site, confirming high specificity for SaCas9 in vivo. (nih.gov)
- Embryos from homozygous polo females have aberrant mitotic spindles that are highly branched and have broad poles. (biologists.org)
- Unlike some coat color dilution lethals, which may result in premature births, stillborn, or weak foals, foals born with lethal white syndrome appear to be fully formed and normal. (wikipedia.org)
- AAV serotype 9-based delivery of the SaCas9 system can efficiently disrupt a disease-causing allele in cardiomyocytes in vivo. (nih.gov)
- SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. (asm.org)
- Van de Walle G, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease. (ugent.be)
- Neuroblast cells in larvae homozygous for mutant alleles of the locus polo show a high frequency of metaphases in which the chromosomes have a circular arrangement, and anaphase figures in which chromosomes appear to be randomly oriented with respect to at least one of the spindle poles. (biologists.org)
- The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A . (aacrjournals.org)
- The mutant character is determined by homozygous recessive alleles, designated pdx-1 , at a single locus. (ias.ac.in)
- This neurografting paradigm circumvents the problem of early lethal tumors at extracerebral sites associated with germ-line p53 deficiency. (uzh.ch)
- Brain tumors arising in this mouse model were highly invasive, reflecting an important feature of the human disease. (uzh.ch)
- In keeping with in vitro data showing that Y236delta has dominant-negative activity, these tumors retained the endogenous wild-type p53 allele but accumulated high levels of Y236delta. (uzh.ch)
- Rhabdoid tumors of early infancy are highly aggressive with consequent poor prognosis. (semanticscholar.org)
- P bodies are a class of highly conserved cytoplasmic granules that have been linked to both mRNA decay and translational repression via general and miRNA-mediated pathways. (biologists.org)
- P bodies are highly conserved cytoplasmic RNPs linked to both mRNA decay and translational repression pathways. (biologists.org)
- 9 Furthermore, caution is warranted for a variant allele that produces multiple mRNA transcripts as both transcript ratios and the functional integrity of the isoforms can affect its clinical relevance. (nature.com)
- Given the proven role of CENH3 in the specification of the centromere, it is of no surprise that null alleles, though transmissible, are lethal as homozygotes [ 13 - 16 ]. (prolekare.cz)
- One allele is a larval lethal, whereas another is semi-lethal with about 7% of homozygotes surviving as adults. (biologists.org)
- In an attempt to identify unknown recessive lethal alleles in the current dairy population, a search using deep Mendelian sampling of 5,288 Jersey cattle was conducted for high-frequency haplotypes that have a deficit of homozygotes at the population level. (jove.com)
- Regarding diseases, in males, having a mutated allele located on the X chromosome. (brainscape.com)
- MICROTUBULE ORGANIZATION 1 (MOR1) is a plant member of the highly conserved MAP215/Dis1 family of microtubule-associated proteins. (plantphysiol.org)
- We hypothesize that Mov10 is elevated in the postnatal brain to suppress retrotransposition, which is highly active during this time in the brain [ 10 ]. (biomedcentral.com)
- Furthermore, understanding the link between lysosomal dysfunction and neurodegeneration is likely to be important for highly prevalent neurodegenerative disorders like Alzheimer's disease. (rupress.org)
- Our data confirm that α1β2γ2 is the major GABA A receptor subtype in the murine brain and demonstrate that, surprisingly, the loss of this receptor subtype is not lethal. (jneurosci.org)
- In the lethal perinatal subtype, the patients show markedly impaired mineralization in utero . (biomedcentral.com)
- RAD50 L1237F was accompanied by LOH of the wild-type allele and mutated a highly conserved residue required for proper MRE11 complex function in DNA repair. (aacrjournals.org)
- Human SMARCB1 wild-type allele is located in the vicinity of 22q11.2 and is approximately 48 kb in length. (semanticscholar.org)
- Our work is focused on the hypothesis, that exposure to low (ineffective) drug concentrations might particularly select for highly resistant and highly competitive MTBC strain populations. (evmedreview.com)