Journal ArticleDOI
No evidence of expansion of CAG or GAA repeats in schizophrenia families and monozygotic twins.
John B. Vincent,Gursharan Kalsi,T. Klempan,Y Tatuch,Robin Sherrington,T. Breschel,Melvin G. McInnis,J Brynjolfsson,H Petursson,H Petursson,Hmd Gurling,Irving I. Gottesman,E.F. Torrey,A Petronis,Juliet Kennedy +14 more
TLDR
Results suggest that trinucleotide repeats found in 12 families from the United Kingdom and Iceland are not involved in the etiology of schizophrenia, and the techniques used for detecting repeat expansions have limits to their sensitivity.Abstract:
Many diseases caused by trinucleotide expansion exhibit increased severity and decreased age of onset (genetic anticipation) in successive generations. Apparent evidence of genetic anticipation in schizophrenia has led to a search for trinucleotide repeat expansions. We have used several techniques, including Southern blot hybridization, repeat expansion detection (RED) and locus-specific PCR to search for expanded CAG/CTG repeats in 12 families from the United Kingdom and 11 from Iceland that are multiplex for schizophrenia and demonstrate anticipation. The unstable DNA theory could also explain discordance of phenotype for schizophrenia in pairs of monozygotic twins, where the affected twin has a greater number of repeats than the unaffected twin. We used these techniques to look for evidence of different CAG/CTG repeat size in 27 pairs of monozygotic twins who are either concordant or discordant for schizophrenia. We have found no evidence of an increase in CAG/CTG repeat size for affected members in the families, or for the affected twins in the MZ twin sample. Southern hybridization and RED analysis were also performed for the twin and family samples to look for evidence of expansion of GAA/TTC repeats. However, no evidence of expansion was found in either sample. Whilst these results suggest that these repeats are not involved in the etiology of schizophrenia, the techniques used for detecting repeat expansions have limits to their sensitivity. The involvement of other trinucleotide repeats or other expandable repeat sequences cannot be ruled out.read more
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Journal ArticleDOI
Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics.
TL;DR: The five newest studies since 1995 from Europe and Japan have confirmed earlier findings on the genetic basis of clinical heterogeneity within schizophrenia and provided further insights into non-inherited factors that contribute to the multifactorial etiology of this disorder.
Journal ArticleDOI
Monozygotic Twins Exhibit Numerous Epigenetic Differences: Clues to Twin Discordance?
Arturas Petronis,Irving I. Gottesman,Peixiang Kan,James L. Kennedy,Vincenzo S. Basile,Andrew D. Paterson,Violeta Popendikyte +6 more
TL;DR: Although the epigenetic analysis was conducted for only several hundred base pairs of DRD2, the fact that numerous studies identified nonuniform methylation patterns across the clones of bisulfite-modified DNA from the same individual, as well as non uniform patterns across different individuals, argues for the universality of intra- and interindividual epigenetic variation.
Journal ArticleDOI
Linkage and associated studies of schizophrenia.
Brien P. Riley,Peter McGuffin +1 more
TL;DR: An assessment of all the linkage studies performed over the past ten years does suggest a number of regions where positive results are found numerous times, including regions on chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 18, 22 and the X.
Journal ArticleDOI
Hippocampal volumes in schizophrenic twins.
Theo G.M. van Erp,Peter A. Saleh,Matti O. Huttunen,Jouko Lönnqvist,Jaakko Kaprio,Oili Salonen,Leena Valanne,Veli-Pekka Poutanen,Carl-Gustav Standertskjöld-Nordenstam,Tyrone D. Cannon +9 more
TL;DR: Although hippocampal volume in healthy individuals is largely affected by genetic factors, it is subject to substantially greater modulation by environmental factors in schizophrenic patients and their relatives.
Journal ArticleDOI
Epigenetic contributors to the discordance of monozygotic twins.
TL;DR: It is argued that not all discordance between monozygotic twins is due to differences in environment, and a number of questions regarding the published results merit a re-assessment in the light of modern molecular insight of the human genome.
References
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Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
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TL;DR: A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.
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Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.
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Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder
Michael Conlon O'Donovan,Carol Guy,Nicholas John Craddock,Timothy Bowen,P. McKeon,António Macedo,W. Maier,D. Wildenauer,Harald N. Aschauer,Sandro Sorbi,E. Feldman,L. Mynett-Johnson,E. Claffey,Benedetta Nacmias,J. Valente,A. Dourado,E. Grassi,E. Lenzinger,A. M. Heiden,S. Moorhead,D. Harrison,Julie Williams,Peter McGuffin,Michael John Owen +23 more