• mutations
  • A large body of literature has appeared on human disease-associated mutations, normal sequence variation, and alterations that acquire pathological significance when combined with other deleterious alleles or second-site mutations. (biomedcentral.com)
  • In contrast, in mutant strains carrying mutations in proteins involved in DNA replication or repair, expansions are frequently seen. (embopress.org)
  • Mutations in the tau gene cause familial frontotemporal dementia. (genetics.org)
  • Recent studies have also found homozygous and compound heterozygous mutations in the TBP gene of SCA17 affected individuals. (cags.org.ae)
  • Her work focuses on studying heritable traits in humans, linking them back to DNA mutations, and using animal models to further explore the mechanisms underlying various phenotypes and the heritability of these phenotypes. (wikipedia.org)
  • First, individuals with autism have significantly reduced fecundity, they are 20 times less likely to have children than average, thus curtailing the persistence of mutations in ASD genes over multiple generations in a family. (wikipedia.org)
  • At this time, there are at least 29 different gene mutations that have been found. (wikipedia.org)
  • intron
  • The reduction in frataxin gene expression may be attributable from either the silencing of transcription of the frataxin gene because of epigenetic modifications in the chromosomal entity or from the inability of splicing the expanded GAA repeats in the first intron of the pre-mRNA as seen in Bacteria and Human cells or both. (wikipedia.org)
  • sequences
  • Iyer, R. R. and Wells, R. D. (1999) Expansion and deletion of triplet repeat sequences in Escherichia coli occur on the leading strand of DNA. (springer.com)
  • The most prevalent repeated sequences in the embedded microsatellite regions were CCT:AGG, CTT:AAG, CTTT:AAAG, and CCCT:AGGG. (wikipedia.org)
  • These strand biased pyrimidine:purine repeating sequences were shown to adopt triple-stranded structures under superhelical stress or at slightly acidic pH. (wikipedia.org)
  • Variations among cloned RU sequences were characterized by the number of microsatellite repeats, and also by the lengths of C and G stretches where triple stranded structures formed. (wikipedia.org)
  • disorders
  • By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology. (nih.gov)
  • Most of these disorders occur at repeat lengths above 35 copies, with a tendency towards further expansion upon successive transmissions. (springer.com)
  • Bowater, R. P. and Wells, R. D. (2000) The intrinsically unstable life of DNA triplet repeats associated with human hereditary disorders. (springer.com)
  • neuronal
  • Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. (nih.gov)
  • We study how synaptic transmission and depolarization cause changes in neuronal gene expression. (stanford.edu)
  • One example of such signaling involves a local increase in Ca2+ concentration near a class of Ca2+ channels (L-type) different from those that trigger presynaptic transmitter release, subsequently leading to activation of an exemplar transcription factor, CREB, a regulator of transcription of many important neuronal genes. (stanford.edu)
  • FRATAXIN
  • This expanded repeat causes R-loop formation, and using a repeat-targeted oligonucleotide to disrupt the R-loop can reactivate frataxin expression. (wikipedia.org)
  • epigenetic
  • Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. (nih.gov)
  • Genetics
  • In 1989, Fu transferred to the Baylor College of Medicine as a post-doctoral fellow to study human genetics. (wikipedia.org)
  • SCA1
  • Research to develop treatments is ongoing and in addition to conventional pharmaceutical treatment, SCA1 has been the subject of such high technology treatment as gene therapy and stem cell therapy. (wikipedia.org)
  • genomes
  • Most human disease genes have been retained in rodent genomes. (biomedcentral.com)
  • The HD gene is found in all human genomes. (wikipedia.org)
  • Haploid human genomes, which are contained in germ cells (the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote ) consist of three billion DNA base pairs , while diploid genomes (found in somatic cells ) have twice the DNA content. (wikipedia.org)
  • While there are significant differences among the genomes of human individuals (on the order of 0.1%), these are considerably smaller than the differences between humans and their closest living relatives, the chimpanzees (approximately 4% ) and bonobos . (wikipedia.org)
  • As of 2012, thousands of human genomes have been completely sequenced, and many more have been mapped at lower levels of resolution. (wikipedia.org)
  • diseases
  • Replication slippage can also lead to other neurodegenerative diseases in humans. (wikipedia.org)
  • In support of this hypothesis, altered expression of a variety of genes has been demonstrated in transgenic mouse models of polyglutamine diseases ( Sugars and Rubinsztein, 2003 ). (jneurosci.org)
  • Although polyglutamine-induced transcriptional dysregulation is likely to be central to the pathogenesis of polyglutamine diseases, it has yet to be elucidated which genes are responsible for the selective neurodegeneration ( Gatchel and Zoghbi, 2005 ). (jneurosci.org)
  • There is a widely held expectation that genomic studies will lead to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including human evolution . (wikipedia.org)
  • An inverse correlation between the repeat length and disease severity/earlier age of onset, known as anticipation, has been observed in most of the families transmitting such types of diseases, suggesting that the length change of the repeats may play a role in the manifestation of anticipation. (springer.com)
  • microsatellites
  • This class of microsatellites has the property of undergoing rapid and sometimes massive expansion of their repeat number, during germline transmission or early embryogenesis. (embopress.org)
  • One striking feature of all expansion‐associated microsatellites is their propensity to form secondary structures. (embopress.org)
  • disease
  • Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. (biomedcentral.com)
  • Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change. (biomedcentral.com)
  • Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. (biomedcentral.com)
  • Differences are revealed in evolutionary conservation and selection between different categories of human disease genes. (biomedcentral.com)
  • Although selection appears not to have greatly discriminated between disease and non-disease genes, synonymous substitution rates are significantly higher for disease genes. (biomedcentral.com)
  • In neurological and malformation syndrome disease systems, associated genes have evolved slowly whereas genes of the immune, hematological and pulmonary disease systems have changed more rapidly. (biomedcentral.com)
  • nevertheless, 15 substituting amino acids associated with human disease were identified as wild-type amino acids in the rat. (biomedcentral.com)
  • Rodent orthologs of human trinucleotide repeat-expansion disease genes were found to contain substantially fewer of such repeats. (biomedcentral.com)
  • although four of these genes are expressed in the brain, none is currently known to be associated with disease. (biomedcentral.com)
  • this suggests that rodent models of human neurological disease are likely to most faithfully represent human disease processes. (biomedcentral.com)
  • The identification of six genes in this study that have multiple characteristics associated with repeat expansion-disease genes raises the possibility that not all human loci capable of facilitating neurological disease by repeat expansion have as yet been identified. (biomedcentral.com)
  • With this information compiled into organized databases [ 3 , 4 ], it is now possible to conduct large-scale, comprehensive analyses of human disease genes. (biomedcentral.com)
  • Here, we summarise current knowledge on experimental models in which to study FRDA cardiomyopathy, with a particular focus on the use of human pluripotent stem cells as a disease model. (curefa.org)
  • Only three motifs, CAG/CTG, CGG/CCG, and GAA/TTC, of the 10 possible trinucleotide repeat permutations have so far been associated with human disease. (springer.com)
  • The gene has also been associated with an increased susceptibility to Late-Onset Parkinson Disease. (cags.org.ae)
  • Repeats of 39 or more uninterrupted CAG triplets cause disease, and longer repeat tracts are correlated with earlier age of onset and faster progression. (wikipedia.org)
  • The size of the repeat correlates with severity of the disease. (wikipedia.org)
  • The lab's current projects include: locating human sleep genes, uncovering the molecular mechanisms of human sleep regulation and human circadian rhythms, investigating mouse models with de/dys-myelinating disease, and classifying miRNAs that contribute to healthy myelin. (wikipedia.org)
  • Humans with this autosomal dominant disease typically go to bed around 7:00 p.m. and wake up at 3:00 a.m. (wikipedia.org)
  • The disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100, and can expand in size when transmitted to successive generations. (wikipedia.org)
  • In 2010, work from Aaron Gitler and Nancy Bonini at the University of Pennsylvania discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing amyotrophic lateral sclerosis (Lou Gehrig's disease). (wikipedia.org)
  • An expansion of the trinucleotide (GCN) repeat from normal 10 to 11-17 at the 5' end of the coding region of this gene leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. (wikipedia.org)
  • The disease is caused by either a recessive or dominant gene. (wikipedia.org)
  • FMR1
  • We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. (nih.gov)
  • A) Predominant CGG-repeat size in the FMR1 promoter as determined by Southern blot analysis. (nih.gov)
  • Knock-out of the Fmr1 gene in mice removes FMRP and mimics FXS in humans ( O'Donnell and Warren, 2002 ). (jneurosci.org)
  • 2001
  • In 2001, Fu and her collaborator's labs published a paper that explained a phenotype of extremely early risers in humans called Familial Advanced Sleep Phase Syndrome (FASPS). (wikipedia.org)
  • polymerase
  • Slippage occurs through five main stages: In the first step, DNA polymerase encounters the direct repeat during the replication process. (wikipedia.org)
  • DNA polymerase reassembles its position on the template strand and resumes normal replication, but during the course of reassembling, the polymerase complex backtracks and repeats the insertion of deoxyribonucleotides that were previously added. (wikipedia.org)
  • One hypothesis is that the increasing number of repeats influence the overall shape of the DNA, which can have an effect on its interaction with DNA polymerase and thus the expression of the gene. (wikipedia.org)
  • nucleotides
  • Nucleotide excision repair proteins are mobilized to this area where one likely outcome is the expansion of nucleotides in the template strand while the other is the absence of nucleotides. (wikipedia.org)
  • promoter
  • It appears to be involved in regulating gene expression based on its location in the nucleus of the cell, its association with promoter regions of several genes, and its interactions with transcriptional regulators and parts of the RNA splicing machinery. (wikipedia.org)