Increased chromosomal breakage in tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

Abstract

Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites.

A Unifying Hypothesis for the Genome Dynamics Proposed to Underlie Neuropsychiatric Phenotypes

“…In 1995, our research group at the University of Pretoria reported a small set of CFSs that could reliably distinguish between Tourette and non-Tourette individuals [34], and in a subsequent publication in 1996 [35] we speculated whether associated (variably) expressed FS could underlie endophenotypes which would explain (a genetic basis for) comorbidity in NPDs. In an evo-devo view, in 1995, Gericke proposed that an 'anthropogenetic' view of behavioral alteration may assist with the elucidation of genetic changes underlying neurobehavioral variation [36].…”

A Unifying Hypothesis for the Genome Dynamics Proposed to Underly Neuropsychiatric Phenotypes

“…In 1995, our research group at the University of Pretoria reported a small set of CFS which could reliably distinguish between Tourette and non-Tourette individuals [34], and in a follow up publication in 1996 [35] we speculated whether associated (variably) expressed FS could underly endophenotypes which would explain (a genetic basis for) comorbidity in NPDs. This concept was considered to imply that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced duplication and recombination following chromosomal strand breakage.…”

Stress Shaping Brains: Higher Order DNA/Chromosome Mechanisms Underlying Epigenetic Programming of the Brain Transcriptome

“…CFS-associated duplication and deletion altering AT tract length and DNA flexibility have been linked with variation in nucleosomal architecture (Cosgrove & Walberger, 2005). AT-rich repeats mediate recombination events in non-homologous chromosomes during meiosis (Jackson et al, 2003) and due to a modification of binding factor characteristics, CFS have been proposed to contribute to epigenetic sensitive phenotypes (Woynarowski, 2004), a phenomenon which has been suggested to include neurobehavioral effects (Garofalo et al,1993;Gericke et al, 1995, Gericke 1998Simonic & Gericke 1996;Simonic & Ott, 1996;Savelyeva et al, 2006).…”