• genetic
  • This finding is helpful for diagnosing MJD, and it is important because MJD is an inherited, slowly progressive disease, and early genetic counseling is usually recommended. (ajnr.org)
  • Family history is an important risk factor for both common complex conditions and single-gene disorders, and it incorporates not only shared genetic susceptibilities but also shared environmental, behavioral, and cultural factors. (aappublications.org)
  • Dr. Jaehong Suh studies the genetic and molecular mechanisms of Alzheimer's disease (AD) and other neurodegenerative disorders, with the aim of identifying novel therapeutic targets and developing effective treatments for patients. (mghmind.org)
  • Additionally, Suh is pursing mechanistic studies on another AD-associated gene, Ataxin-1, which was found recently in a genetic screen of AD families. (mghmind.org)
  • It was difficult to determine if the disease had a genetic component, since most families only have one person affected with the disorder. (wikipedia.org)
  • ATXN1 is the gene mutated in spinocerebellar ataxia type 1 (SCA1), a dominantly-inherited, fatal genetic disease in which neurons in the cerebellum and brain stem degenerate over the course of years or decades. (wikipedia.org)
  • Genetic testing looks at the number of CAG repeats within the coding region of the MJD/ATXN3 gene on chromosome 14. (wikipedia.org)
  • Prior to the understanding of the genetic mechanism for anticipation, it was debated whether anticipation was a true biological phenomenon or whether the earlier age of diagnosis was related to heightened awareness of disease symptoms within a family. (wikipedia.org)
  • The genetic basis was discovered in 1993 by an international collaborative effort led by the Hereditary Disease Foundation. (wikipedia.org)
  • The diagnosis of oculopharyngeal muscular dystrophy can be done via two methods, a muscle biopsy or a blood draw with genetic testing for GCG trinucleotide expansions in the PABPN1 gene. (wikipedia.org)
  • Although the transfer of a number of genes from these organelles to the nucleus prevents them from living independently, each still possesses genetic material in the form of double stranded DNA. (wikipedia.org)
  • Because this grouping of diseases is of heterogenic origin, the causes can be singular or additive consequences of genetic, toxic, or nutritional stress. (wikipedia.org)
  • Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity. (wikipedia.org)
  • fragile X syndro
  • Specific model conditions were presented that illustrated issues involved in the use of family history information in pediatric settings, including cystic fibrosis, fragile X syndrome, polycystic kidney disease, hyperlipidemia and coronary artery disease, and birth defects. (aappublications.org)
  • While there, she was part of the team that identified the fragile-X syndrome gene. (wikipedia.org)
  • 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome. (wikipedia.org)
  • genome
  • The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. (biomedcentral.com)
  • Recent results suggest that most of the vast quantities of noncoding DNA within the genome have associated biochemical activities, including regulation of gene expression , organization of chromosome architecture , and signals controlling epigenetic inheritance . (wikipedia.org)
  • The estimate of the number of human genes has been repeatedly revised down from initial predictions of 100,000 or more as genome sequence quality and gene finding methods have improved, and could continue to drop further. (wikipedia.org)
  • Basic information about these molecules and their gene content, based on a reference genome that does not represent the sequence of any specific individual, are provided in the following table. (wikipedia.org)
  • Trinucleotide repeats are apparent in a number of loci in the human genome. (wikipedia.org)
  • GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 8 Human ATXN8OS genome location and ATXN8OS gene details page in the UCSC Genome Browser. (wikipedia.org)
  • For example, more than a million copies of the Alu sequence are present in the human genome, and these sequences have now been recruited to perform functions such as regulating gene expression. (wikipedia.org)
  • proteins
  • 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)
  • If these repeats are found in coding regions then the variations to the polynucleotide sequence can result in the formation of abnormal proteins in eukaryotes. (wikipedia.org)
  • As normal copies of disease genes likely encode essential proteins, normal allele haploinsuffi-ciency may contribute to myopathic phenotypes as well. (fitness-vip.com)
  • At MGH, Suh has also studied the role of FE56 and FE65L1 APP-binding proteins on APP processing in neurons and identified abnormal eye and muscle phenotypes in the knockout mice for the two genes. (mghmind.org)
  • Mitochondria, however, depend on other proteins that are encoded by nuclear genes, constructed in the cytoplasm and then transported into the mitochondria. (wikipedia.org)
  • different genes
  • Type I strains are specified by the gene called MatA, Type II stains have three different genes: MatB (homologous to Mat A), Mat C, and Mat D, and Type III strains have Mat S and Mat T genes (which are homologous to Mat C and Mat D). These sexes can only mate with the two different sexes and not with its own. (wikipedia.org)
  • Novel genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions. (wikipedia.org)
  • phenotype
  • Soluble N-terminal mHTT fragments are thought to be the main drivers of disease progression 7 and mouse models of HD that express these fragments have a rapidly progressive phenotype 8 . (plos.org)
  • Fu traced the phenotype back to a point mutation in a gene called DEC2 that is associated with short sleep phenotype in humans. (wikipedia.org)
  • Thus, the phenotype of traits linked to genes found in either chloroplasts or mitochondria are determined exclusively by the maternal parent. (wikipedia.org)
  • symptoms
  • The dysfunction and eventual death of neurons in these areas of the brain underlie the signs and symptoms of Huntington disease. (sterding.com)
  • A larger number of repeats is usually associated with an earlier onset of signs and symptoms. (sterding.com)
  • 1000 and is tightly correlated with age of onset and severity of the disease symptoms. (curefa.org)
  • Some symptoms, such as clumsiness and rigidity, make MJD commonly mistaken for drunkenness or Parkinson's disease. (wikipedia.org)
  • citation needed] MJD can be diagnosed by recognizing the symptoms of the disease and by taking a family history. (wikipedia.org)
  • Physicians ask patients questions about the kind of symptoms relatives with the disease had, the progression and harshness of symptoms, and the ages of onset in family members. (wikipedia.org)
  • A limitation to this test is that if the number of CAG repeats in an individual being tested falls between the healthy and pathogenic ranges (45-60 repeats), then the test cannot predict whether an individual will have MJD symptoms. (wikipedia.org)
  • All of these diseases have neurological symptoms. (wikipedia.org)
  • Once the number of copies reaches over 100, the disease will manifest earlier in life (although the individual will still reach adulthood before the symptoms are evident) and the symptoms will be more severe - including electrical myotonia. (wikipedia.org)
  • female carriers tend to have a relatively mild expression of the disease if they show symptoms at all. (wikipedia.org)
  • About eight percent of cases start before the age of 20 years and typically present with symptoms more similar to Parkinson's disease. (wikipedia.org)
  • Current research directions include determining the exact mechanism of the disease, improving animal models to aid with research, testing of medications to treat symptoms or slow the progression of the disease, and studying procedures such as stem cell therapy with the goal of repairing damage caused by the disease. (wikipedia.org)
  • Less commonly, OPMD can be inherited in an autosomal recessive pattern, which means that two copies of the mutated gene need to be present in each cell, both parents need to be carriers of the mutated gene, and usually show no signs or symptoms. (wikipedia.org)
  • Currently no cure or specific treatment exists to eliminate the symptoms or stop the disease progression. (wikipedia.org)
  • sequence
  • In the present study, we have used a collection of nearly 1,200 human disease gene sequences to perform a large-scale analysis of gene and sequence conservation. (biomedcentral.com)
  • There is a CAG repeat in the coding sequence which is longer in humans than other species (6-38 uninterrupted CAG repeats in healthy humans versus 2 in the mouse gene). (wikipedia.org)
  • Gene conversion arises during DNA repair via DNA recombination, by which a piece of DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. (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)
  • Purification of genomic DNA from each patient's blood sample was carried out and the expansion of CTG repeats in the third intron of TCF4 was subsequently examined by polymerase chain reaction (PCR). (arvojournals.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)
  • polyglutamine
  • How polyglutamine expansion in Ataxin-1 causes neuronal dysfunction and degeneration is still unclear. (wikipedia.org)
  • The polyglutamine tract in affected pedigrees tends to increase in length over generations, a phenomenon known as "anticipation", leading to an increase in the severity of the disease as well as a decrease in the age of onset for each subsequent generation of a family affected by SBMA. (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)
  • causative gene
  • In August 1999, 16 years after meeting her first patient with Rett syndrome, Zoghbi and collaborators identified MECP2 as the causative gene. (wikipedia.org)
  • individuals
  • the repeat ranged from 6 to 54 in individuals with normal X chromosomes. (wikipedia.org)
  • This repeat is prone to errors in DNA replication and can vary widely in length between individuals. (wikipedia.org)
  • The test will show positive for MJD if this region contains 61-87 repeats, as opposed to the 12-44 repeats found in healthy individuals. (wikipedia.org)
  • However, assigning individuals to a specific sub-type of the disease is of limited clinical significance. (wikipedia.org)
  • Between 5 and 37 repeats is considered normal, while individuals with between 38 and 49 repeats are considered to have a pre-mutation and are at risk of having children with further expanded repeats and, therefore, symptomatic disease. (wikipedia.org)
  • Parkinson's
  • 3 Clinical diagnosis of PD was made in accordance with the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria. (ajnr.org)
  • biochemical
  • Our approach is to combine physiological approaches (how fast, how steeply voltage-dependent, how is signal transduced) and biochemical experiments using cDNA microarrays (which genes, in what context, what relationship to learning and memory). (stanford.edu)
  • neuronal
  • 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)
  • 1993
  • On the same day in April 1993, both Zoghbi and Orr identified ATXN1 as the gene responsible for SCA1. (wikipedia.org)
  • hairpin
  • The RNA from the expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due to the extensive hydrogen bonding between C-G base pairs, and it has been demonstrated that these sequester the splicing regulator MBNL1 to form distinctive foci by labelling it with GFP and a probe oligonucleotide with the red-fluorescent dye Cyanine5 (Cy5) DM2 is caused by a defect of the CNBP gene on chromosome 3. (wikipedia.org)