Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13.
OBJECTIVE
To localize genes influencing the susceptibility to Gilles de la Tourette syndrome (GTS) and associated chronic multiple tics (CMT).


METHODS
A single, large, multiple affected pedigree containing 35 subjects diagnosed with GTS and a further 14 with CMT was genotyped for markers spanning the autosomes. Linkage analysis was carried out using classical lod score analysis and model-free lod score analysis. All markers were subjected to two-point analysis, and markers producing a two-point result significant at P<0.005 were subjected to three-point analysis using adjacent markers.


RESULTS
The following markers produced at least one result significant at 0.005 using two-point analysis: D5S1981, D5S2050, D10S591, D10S189, D13S217, and D14S288. Three-point analysis with D5S2050 and D5S400 produced a lod of 2.9 with CMT. Three-point analysis of D10S591 and D10S189 produced lods of 1.9 with GTS and CMT. Three-point analysis of D13S217 and D13S171 produced a lod of 2.7 with GTS. No single haplotype appeared to account for the majority of cases within the pedigree.


CONCLUSIONS
It seems likely that more than one susceptibility allele is present in the pedigree. Although none of the three positive regions is conclusively implicated, it seems probable that at least one contains a susceptibility locus. We recommend that association-based studies be carried out in these three regions to produce further evidence for a localization and to carry out fine-mapping.
Curtis
D
D
Department of Psychiatry, St. Bartholomew's and Royal London School of Medicine and Dentistry, UK. dcurtis@hgmp.mrc.ac.uk
Brett
P
P
Dearlove
A M
AM
McQuillin
A
A
Kalsi
G
G
Robertson
M M
MM
Gurling
H M D
HM
D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008297:Male; D010375:Pedigree; D005879:Tourette Syndrome / Q000235:genetics*
D005819:Genetic Markers