• SCA1
  • A total of 14 South African kindreds and 22 sporadic individuals with SCA were investigated for the expanded SCA1 and MJD repeats. (springer.com)
  • Expanded SCA1 and CAG repeats were found to cosegregate with the disorder in six of the families tested and were also observed in one sporadic individual with a negative family history of SCA. (springer.com)
  • The use of the microsatellite markers D6S260, D6S89 and D6S274 provided evidence that the expanded SCA1 repeats segregated with three distinct haplotypes in the six families. (springer.com)
  • 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)
  • genetic
  • Wells, R. D. (1996) Molecular basis of genetic instability of triplet repeats. (springer.com)
  • 4 , 5 So far, many genes have been attributed to cause this disease, thereby revealing its genetic complexity. (arvojournals.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)
  • Together, these discoveries characterized the molecular basis of genetic "anticipation," the phenomenon of worsening severity in subsequent generations, as being due to unstable, expanded trinucleotide repeats. (wikipedia.org)
  • Widespread DNA polymorphism has been exploited through the use of restriction enzymes and, more recently, the polymerase chain reaction to create genetic markers and detect linkage to a growing list of human disease genes. (acnp.org)
  • A growing number of molecular genetic studies aimed at identifying disease genes is now being added to this foundation of classical genetics. (acnp.org)
  • Genetic analyses of these pedigrees indicate that a multifactorial-threshold model provides a plausible explanation of the transmission and that a single locus model can be excluded (26, 29). (acnp.org)
  • Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder. (wikipedia.org)
  • The increasing availability of DNA amplification by PCR at the beginning of the 1990s triggered a large number of studies using the amplification of microsatellites as genetic markers for forensic medicine, for paternity testing, and for positional cloning to find the gene underlying a trait or disease. (wikipedia.org)
  • Microsatellite
  • A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from 1-6 or more base pairs) are repeated, typically 5-50 times. (wikipedia.org)
  • 1992). A microsatellite is a tract of tandemly repeated (i.e. adjacent) DNA motifs that range in length from one to six or up to ten nucleotides (the exact definition and delineation to the longer minisatellites varies from author to author), and are typically repeated 5-50 times. (wikipedia.org)
  • nucleotides
  • Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements. (wikipedia.org)
  • 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)
  • The letters stand for three nucleotides (complex organic molecules) known as cytosine, thymine, and guanine, and are repeated a certain number of times. (thefreedictionary.com)
  • Repeat units of four and five nucleotides are referred to as tetra- and pentanucleotide motifs, respectively. (wikipedia.org)
  • chromosomes
  • Telomeres are repeating DNA sequences at the tip ends of the chromosomes that are diverse in length and in humans can reach a length of 15,000 base pairs. (jove.com)
  • In contrast, elongation is partially modulated by the enzyme telomerase, which adds repeating sequences to the ends of the chromosomes. (jove.com)
  • These laws describe the inheritance of traits linked to single genes on chromosomes in the nucleus. (wikipedia.org)
  • the repeat ranged from 6 to 54 in individuals with normal X chromosomes. (wikipedia.org)
  • Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. (biomedcentral.com)
  • The alleles at the same locus on the two homologous chromosomes may be identical or different. (wikipedia.org)
  • The telomeres at the ends of the chromosomes, thought to be involved in ageing/senescence, consist of repetitive DNA, with the hexanucleotide repeat motif TTAGGG in vertebrates. (wikipedia.org)
  • instability
  • Tandem repeat instability and its effect on cancer phenotypes remain so far poorly studied on a genome-wide scale. (biomedcentral.com)
  • Specifically, we study for the first time genome-wide repeat instability in the promoters and exons of 18,439 genes, and examine the association of repeat instability with genome-scale gene expression levels. (biomedcentral.com)
  • Our results suggest that repeat instability in gene promoters and associated differential gene expression may play an important role in colorectal tumors, which is a first step towards the development of more effective molecular diagnostic approaches centered on repeat instability. (biomedcentral.com)
  • fragile X syndro
  • Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. (nih.gov)
  • While there, she was part of the team that identified the fragile-X syndrome gene. (wikipedia.org)
  • This gene is responsible for the fragile X syndrome. (readbyqxmd.com)
  • thus
  • 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)
  • Thus, each gene also has a corresponding homologue, which may exist in different versions called alleles. (wikipedia.org)
  • FMR1
  • Dr. Warren organized and led an international effort that isolated the FMR1 gene responsible for this syndrome in 1991. (pedsresearch.org)
  • Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. (nih.gov)
  • 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)
  • 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)
  • A) Predominant CGG-repeat size in the FMR1 promoter as determined by Southern blot analysis. (nih.gov)
  • 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 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)
  • Molecular
  • 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)
  • intronic
  • We tested for an association between an intronic TGC trinucleotide repeat in TCF4 and FECD by determining repeat length in 66 affected participants with severe FECD and 63 participants with normal corneas in a 3-stage discovery/replication/validation study. (jove.com)
  • alleles
  • Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. (wikipedia.org)
  • More generally, where a gene exists in two allelic versions (designated A and a), three combinations of alleles are possible: AA, Aa, and aa. (wikipedia.org)
  • humans
  • This elongation is variable in length, with as few as 6 and as many as 81 repeats reported in humans. (wikipedia.org)
  • Most vertebrates have two orthologs of the gene (called ATXN2 and ATXN2L in humans), with the exception of birds which only have one. (wikipedia.org)
  • whereas genes
  • 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)
  • several genes
  • 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)
  • pathological
  • In any of the inherited cases, specific genes have been identified, although in most cases the precise way in which the genes exert a pathological influence is not known. (medscape.com)
  • 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)
  • genetically
  • Such genetically isolated populations are ideal for linkage studies because their gene pools are typically more homogeneous than those of the general population. (acnp.org)
  • TCF4
  • Variation in the transcription factor 4 (TCF4) gene has been identified as a major contributor to the disease. (jove.com)
  • found
  • This results in some repeats found in the template strand being replicated twice into the daughter strand. (wikipedia.org)
  • 7 by conducting genome-wide linkage scan and association with 64 multiplex Caucasian families where they identified rs613872 to be coinciding with the FECD2 locus previously found by Sundin and colleagues. (arvojournals.org)
  • in this case, the germ cells produced have a greater number of repeats than are found in the somatic tissues. (wikipedia.org)
  • When the repeat is present in an untranslated region, it could affect the expression of the gene in which the repeat is found (ex. (wikipedia.org)
  • Introns are found in the genes of most organisms and many viruses, and can be located in a wide range of genes, including those that generate proteins , ribosomal RNA (rRNA), and transfer RNA (tRNA). (wn.com)
  • In cell-based assays, it was found that these mutant channels aggregate in the endoplasmic reticulum, not dissimilar from that seen in the CAG expansion mutants above. (wikipedia.org)