DNA Expansions
Nucleic Acids Metabolism

Author: Gianpiero Pescarmona
Date: 24/02/2010


Diseases of Unstable Repeat Expansion: Mechanisms and Common Principles 2005

Expandable DNA repeats and human disease 2007

"Trinucleotide repeat disorder":

  • DNA trinucleotide repeat expansion in neuropsychiatric patients. 2003
    Med Sci Monit. 2003 Sep;9(9):RA237-45. Mohmood S, Sherwani A, Khan F, Khan RH, Azfer A.
    Dynamic mutations in human genes result from unstable trinucleotide repeats which are expanded within the genome. These expansions of trinucleotide repeats have been shown to be the etiological factors in various neuropsychiatric diseases and other genetic disorders. This hypothesis is supported by various independent studies showing large expansion of trimeric repeats, such as CAG/CTG/CCG/CGG/AAG, in patient DNA samples. These repeats are also identified in other disease loci not clearly related to particular diseases, which indicates that such expansions are one of the general forms of evolution occurring throughout the human genome. The trinucleotide repeat expansions occur during meiosis and are generally irreversible. Accumulation of these repeats over generations eventually ends in a deficiency of replication. There is evidence that certain ethnic groups in the human population have predispositions for expanded repeats related to neuropsychiatric diseases. It is likely that racial/ethnic differences reflect variations, which suggests the possibility of an underlying complex biological process. The present review highlights the importance of repeat expansions in some neuropsychiatric diseases, such as spinal and bulbular atrophy (SBMA), spinocerebellar ataxia (SCA), Huntington's disease (HD), schizophrenia, myotonic dystrophy (DM) and fragile-X syndrome.
  • CCG repeats in cDNAs from human brain. Hum Genet. 1998 Dec;103(6):666-73. Kleiderlein JJ, Nisson PE, Jessee J, Li WB, Becker KG, Derby ML, Ross CA, Margolis RL.
    Expansion mutations of trinucleotide repeats and other units of unstable DNA have been proposed to account for at least some of the genetic susceptibility to a number of neuropsychiatric disorders, including bipolar affective disorder, schizophrenia, autism, and panic disorder. To generate additional candidate genes for these and other disorders, cDNA libraries from human brain were probed at high stringency for clones containing CCG, CGC, GCC, CGG, GCG, and GGC repeats (referred to collectively as CCG repeats). Some 18 cDNAs containing previously unpublished or uncharacterized repeats were characterized for chromosomal locus, repeat length polymorphism, and similarity to genes of known function. The cDNAs were also compared with the 37 human genes with eight or more consecutive CCG triplets in GenBank. The repeats were mapped to a number of loci, including 1p34, 2p11.2, 2q30-32, 3p21, 3p22, 4q35, 6q22, 7qter, 13p13, 17q24, 18p11, 19p13.3, 20q12, 20q13.3, and 22q12. Length polymorphism was detected in 50% of the repeats. The newly cloned cDNAs include a complete transcript of human neurexin-1B, a portion of BCNG-1 (a newly described brain-specific ion channel), a previously unreported polymorphic repeat located in the 5' UTR region of the guanine nucleotide-binding protein (G-protein) beta2 subunit, and a human version of the mouse proline-rich protein 7. This list of cDNAs should expedite the search for expansion mutations associated with diseases of the central nervous system.
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