• deleterious
  • In short, frequency-based methods try to exploit the fact that mutations under positive Darwinian selection fix in the population with a higher rate than neutral or deleterious mutations. (genetics.org)
  • The rejection of the hot spot model and lack of rejection of a selection model for the C755G mutation, along with other data, provides strong support for the proposal that positive selection in the testis can act to increase the frequency of premeiotic germ cells carrying a mutation deleterious to an offspring, thereby unfavorably altering the mutational load in humans. (pubmedcentralcanada.ca)
  • genetic
  • This evolution is a complex stochastic process where the major evolutionary forces, mutation, genetic drift, and selection all contribute to the observed evolutionary changes, making their individual roles difficult to disentangle. (genetics.org)
  • The frequency of the most common sporadic Apert syndrome mutation (C755G) in the human fibroblast growth factor receptor 2 gene (FGFR2) is 100-1,000 times higher than expected from average nucleotide substitution rates based on evolutionary studies and the incidence of human genetic diseases. (pubmedcentralcanada.ca)
  • Studying the anatomical distribution of germline mutations can provide new insights into genetic disease and evolutionary change. (pubmedcentralcanada.ca)
  • Understanding and estimating the genetic hazards of exposure to chemical mutagens and anticancer drugs in humans requires the development of efficient systems for monitoring germ line mutation. (aacrjournals.org)
  • The results of this study show that the single-molecule PCR technique provides a new and efficient experimental system for monitoring the genetic effects of anticancer drugs, capable of detecting increases in mutation rates at clinically relevant doses of exposure. (aacrjournals.org)
  • The analysis of germ line mutation induction in mice currently provides the main source of experimental data for evaluating the genetic risk of exposure to chemical mutagens and anticancer drugs in humans ( 4 , 6 ). (aacrjournals.org)
  • Given that these are the doses of most concern to genetic toxicology, the development of new, more sensitive and efficient approaches for evaluating the germ line effects of chemical mutagens is warranted. (aacrjournals.org)
  • These studies indicate that regional mutation rates are influenced by various properties of the genome and that no single factor can explain the observed patterns of genetic diversity and divergence in humans. (pubmedcentralcanada.ca)
  • Mutations in the GBA gene are the most common genetic cause of Parkinson s disease. (michaeljfox.org)
  • Furthermore, specific mutations that occur as a result of a recombination between the gene and the pseudogene are often missed by the traditional genetic methods. (michaeljfox.org)
  • To further address this issue, 266 subjects from 194 HPC families participating in the Seattle-based Prostate Cancer Genetic Research Study were screened for BRCA2 mutations by sequencing the coding regions, intron-exon boundaries, and suspected regulatory elements of this gene. (aacrjournals.org)
  • In biology and genetics, the germline in a multicellular organism is the population of its bodily cells that are so differentiated or segregated that in the usual processes of reproduction they may pass on their genetic material to the progeny. (wikipedia.org)
  • According to this view mutations, recombinations and other genetic changes in the germline may be passed to offspring, but a change in a somatic cell will not be. (wikipedia.org)
  • Weismann however worked long before such mechanisms were known, let alone epigenetic mechanisms or even the genetic role of chromosomes, and he believed that there was some clear qualitative difference between germ cells and somatic cells, though he did realise that the somatic cells differentiated from the germ cells. (wikipedia.org)
  • gene that encodes
  • Currently, the most reliable way to predict whether a colorectal cancer patient will respond to one of the EGFR-inhibiting drugs is to test for certain "activating" mutations in the gene that encodes KRAS, which occurs in 30%-50% of colorectal cancers. (wikipedia.org)
  • King-Denborough syndrome has been linked to a mutation on chromosome 19 located near the gene that encodes the ryanodine receptor whereas Noonan syndrome is associated with a mutation on chromosome 12. (wikipedia.org)
  • whole genome
  • We investigated global patterns of germline mutation by whole genome sequencing of monozygotic twins concordant for ASD and their parents. (pubmedcentralcanada.ca)
  • This was previously estimated using paleontological calibrations (especially the human/chimp split), but a slower mutation rate emerged on the basis of whole genome data from humans. (blogspot.com)
  • There may be problems with the latter (because of false positive/negative mutations using whole genome sequencing), but the problem is an important one due to the use of the mutation rate to estimate time depth of common ancestry. (blogspot.com)
  • amino acid
  • Methods to find driver mutations are usually classified into two main categories: mutation frequency-based analysis and bioinformatic predictions of functional effects of amino acid changes. (genetics.org)
  • A single amino acid substitution, and in particular a single nucleotide substitution, is responsible for an activating mutation. (wikipedia.org)
  • The mutation causes an amino acid change from arginine to histidine at codon 337. (wikipedia.org)
  • loci
  • We calibrate a scoring system from protein domain alignments to score mutations and their target loci. (genetics.org)
  • YHRD has updated with new mutation rates for Y-STR loci. (blogspot.com)
  • Unstable ESTR loci consist of homogenous arrays of short repeats (4-6 bp) and show very high spontaneous mutation rates in the mouse germ line, observed as size changes in the alleles of these loci ( 10 - 12 ). (aacrjournals.org)
  • Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. (blogspot.com)
  • increase in mutation
  • Exposure to procarbazine led to a maximal increase in mutation frequency at 50 mg/kg, with a plateau at the higher concentrations. (aacrjournals.org)
  • 1) The only data point from the YRI family that we have suggests that there is a 5-fold increase in mutation rate from the maternal YRI contribution relative to the CEU maternal contribution. (blogspot.com)
  • recurrent
  • A recent study of familial and early onset prostate cancer reported a recurrent rare germline mutation of HOXB13 among men of European descent. (aacrjournals.org)
  • The germline mutation G84E of HOXB13 is a rare but recurrent mutation associated with elevated risk of prostate cancer in men of European descent, with an effect size that is greater than observed for previously validated risk variants of genome wide association studies. (aacrjournals.org)
  • protein
  • Most of the inherited SDHC gene mutations change single amino acids in the SDHC protein sequence or result in a shortened protein. (wikipedia.org)
  • Mutations in the Ras/mitogen activated protein kinase signaling pathways are known to be responsible for ~70% of NS cases. (wikipedia.org)
  • mutagens
  • The suitability of a single-molecule PCR-based approach for monitoring mutation induction at the mouse expanded simple tandem repeat (ESTR) locus Ms6-hm by chemical mutagens and anticancer drugs has been validated. (aacrjournals.org)
  • Most importantly, these tests lack the sensitivity to detect mutation induction in the germ line of mice exposed to low and often intermediate concentrations of chemical mutagens. (aacrjournals.org)
  • sporadic
  • Current methods to measure directly the frequency at which human germline nucleotide substitutions arise each generation include the analysis of sporadic cases of human autosomal dominant or sex-linked diseases [ 1 , 2 ] and DNA analysis of sperm [ 3 - 5 ]. (pubmedcentralcanada.ca)
  • Within a case-control series of that study, the mutation was detected in 45 of 2,064 (2.2%) familial cases, in 19 of 2,410 (0.8%) sporadic cases, and in one of 1,401 (0.07%) controls. (aacrjournals.org)
  • A high proportion of cases may represent new, sporadic mutations. (wikipedia.org)
  • transversion
  • 8-Oxoguanine, an oxidized derivative of guanine, is produced by spontaneous oxidation in the germline cells of mice, and during the cell's DNA replication cause GC to TA transversion mutations. (wikipedia.org)
  • populations
  • We are still assuming that all populations have the same genome mutation rate. (blogspot.com)
  • There are a number of lines of evidence to suggest that there may be differences between populations on mutation frequency. (blogspot.com)
  • 2) Evidence suggests that the SNP : microsatellite mutation ratio is increased in Sub-Saharan populations relative to Eurasians. (blogspot.com)
  • 3) There is strong evidence that differences in PDRM9 between populations dramatically shifts recombination hotspots and linkage disequilibrium patterns across populations, why couldn't SNP mutations also differ across populations? (blogspot.com)
  • There are many other reasons to suspect differences of mutation frequency between populations, but I think it is something that people don't like to discuss because it will mean going back to the drawing board on a number of critical assumptions that we have made about human history. (blogspot.com)
  • Genetics
  • therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. (blogspot.com)
  • syndrome
  • Unique Brazilian Mutation: Although other mutations leading to Li-Fraumeni syndrome have been found outside the DNA-binding domain, a mutation at codon 337 of the tetramerization domain of TP53 has shown a particularly high frequency. (wikipedia.org)
  • variation
  • We show first that this score predicts to a good degree the rate of polymorphism of the observed germline variation. (genetics.org)
  • Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). (blogspot.com)
  • frequency
  • To determine if this increased frequency was due to the nucleotide site having the properties of a mutation hot spot, or some other explanation, we developed a new experimental approach. (pubmedcentralcanada.ca)
  • We examined the spatial distribution of the frequency of the C755G mutation in the germline by dividing four testes from two normal individuals each into several hundred pieces, and, using a highly sensitive PCR assay, we measured the mutation frequency of each piece. (pubmedcentralcanada.ca)
  • This unusually high frequency suggests that something about that DNA base or its local surroundings makes it highly susceptible to mutation. (pubmedcentralcanada.ca)
  • We propose that these mutations arise at the expected rate, but that mutated cells gain a selective advantage that allows them to increase their frequency compared to nonmutant cells. (pubmedcentralcanada.ca)
  • The frequency of ESTR mutation was evaluated in the germ line of male mice exposed to the well-characterized alkylating agent and mutagen, ethylnitrosourea, and four widely used anticancer drugs, bleomycin, cyclophosphamide, mitomycin C, and procarbazine. (aacrjournals.org)
  • found
  • I found that Chandlers germ-line rates worked well in estimating TMRCA for a scottish clan of known historical origin. (blogspot.com)
  • We found that mutant cells were not uniformly distributed throughout the testes, as would be expected for random mutations. (pubmedcentralcanada.ca)
  • The dose-response of ethylnitrosourea-induced mutation was found to be very close to that previously established using a pedigree-based approach for ESTR mutation detection. (aacrjournals.org)
  • stem cells
  • It is now known in some detail that this distinction between somatic and germ cells is partly artificial and depends on particular circumstances and internal cellular mechanisms such as telomeres and controls such as the selective application of telomerase in germ cells, stem cells and the like. (wikipedia.org)
  • Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in a cell culture such as the HeLa cell line, and specific stem cells such as germ cells (producing ova and spermatozoa). (wikipedia.org)
  • The renewal of ovarian follicles from germline stem cells (originating from bone marrow and peripheral blood) has been reported in the postnatal mouse ovary. (wikipedia.org)
  • tissue
  • Total RNA was isolated from tumor tissue or tumor cell lines using TRIzol (Life Technologies, Inc.), and DNA from normal and tumor tissue was extracted with DNAzol (Life Technologies, Inc. (aacrjournals.org)
  • Understanding why a mutation can be suppressed in one tissue but not others stands to unlock insights into tissue-specific transcriptional regulation and how these programs promote fragility or resistance of cancer-causing mutations. (labroots.com)
  • Using a comprehensive tissue expression atlas from the FANTOM5 consortium, we have access to CAGE sequencing data that captures promoter usage and gene expression in over 1000 human samples, including primary cells, tissues and cell lines. (labroots.com)
  • families
  • However, few studies have assessed the contribution of such mutations in HPC families, and results have been inconsistent across studies ( 18 - 20 ). (aacrjournals.org)
  • replication
  • This is because spermatocytes go through a larger number of cell divisions throughout a male's life, resulting in more replication cycles that could result in a DNA mutation. (wikipedia.org)
  • The father's sperm, on the other hand, undergoes continuous replication throughout his lifetime, resulting in many small point mutations that result from errors in replication. (wikipedia.org)
  • In germline cells, ROS are likely a significant cause of DNA damages that, upon DNA replication, lead to mutations. (wikipedia.org)
  • cell
  • This is true regardless of whether mutation is dependent or independent of cell division. (pubmedcentralcanada.ca)
  • As August Weismann proposed and pointed out, a germline cell is immortal in the sense that it is part of a lineage that has reproduced indefinitely since the beginning of life and, barring accident could continue doing so indefinitely. (wikipedia.org)
  • Plants and basal metazoans such as sponges (Porifera) and corals (Anthozoa) do not sequester a distinct germline, generating gametes from multipotent stem cell lineages that also give rise to ordinary somatic tissues. (wikipedia.org)
  • BAP1 somatic mutations were identified in a small number of breast and lung cancer cell lines, but BAP1 was first shown to act as a tumor suppressor in cultured cells, where its deubiquitinase (UCH) domain and Nuclear localization sequences were required for BAP1 to suppress cell growth. (wikipedia.org)