Biomaterial Database

Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. 2012

P Paschou, and E Stylianopoulou, and I Karagiannidis, and R Rizzo, and Z Tarnok, and T Wolanczyk, and J Hebebrand, and M M Nöthen, and G Lehmkuhl, and L Farkas, and P Nagy, and U Szymanska, and D Lykidis, and C Androutsos, and V Tsironi, and A Koumoula, and C Barta, and S Klidonas, and P Ypsilantis, and C Simopoulos, and , and G Skavdis, and M Grigoriou

Department of Molecular Biology and Genetics, Democritus University of Thrace, Panepistimioupoli, Dragana, Greece. ppaschou@mbg.duth.gr

The etiology and pathophysiology of Tourette Syndrome (TS) remain poorly understood. Multiple lines of evidence suggest that a complex genetic background and the cortico-striato-thalamo-cortical circuit are involved. The role of Lhx6 and Lhx8 in the development of the striatal interneurons, prompted us to investigate them as novel candidate genes for TS. We performed a comparative study of the expression of Lhx6 and Lhx8 and investigated genetic association with TS using two samples of trios (TSGeneSEE and German sample - 222 families). We show that Lhx6 and Lhx8 expression in the forebrain is evolutionarily conserved, underlining their possible importance in TS-related pathophysiological pathways. Our tagging-single nucleotide polymorphism (tSNP)-based association analysis was negative for association with LHX8. However, we found positive association with LHX6 in the TSGeneSEE sample (corrected P-value = 0.006 for three-site haplotype around SNP rs3808901) but no association in the sample of German families. Interestingly, the SNP allele that was identified to be significantly associated in the TSGeneSEE dataset, showed an opposite trend of transmission in the German dataset. Our analysis of the correlation of the LHX6 region with individual ancestry within Europe, revealed the fact that this particular SNP demonstrates a high degree of population differentiation and is correlated with the North to South axis of European genetic variation. Our results indicate that further study of the LHX6 gene in relation to the TS phenotype is warranted and suggest the intriguing hypothesis that different genetic factors may contribute to the etiology of TS in different populations, even within Europe.

UI	MeSH Term	Description	Entries
D007395	Interneurons	Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.	Intercalated Neurons,Intercalated Neuron,Interneuron,Neuron, Intercalated,Neurons, Intercalated
D008297	Male		Males
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D005260	Female		Females
D005879	Tourette Syndrome	A neuropsychological disorder related to alterations in DOPAMINE metabolism and neurotransmission involving frontal-subcortical neuronal circuits. Both multiple motor and one or more vocal tics need to be present with TICS occurring many times a day, nearly daily, over a period of more than one year. The onset is before age 18 and the disturbance is not due to direct physiological effects of a substance or another medical condition. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. (From DSM-IV, 1994; Neurol Clin 1997 May;15(2):357-79)	Gilles de la Tourette Disorder,Gilles de la Tourette's Disease,Tic Disorder, Combined Vocal and Multiple Motor,Chronic Motor and Vocal Tic Disorder,Combined Multiple Motor and Vocal Tic Disorder,Combined Vocal and Multiple Motor Tic Disorder,Gilles De La Tourette's Syndrome,Gilles de la Tourette Syndrome,Multiple Motor and Vocal Tic Disorder, Combined,Tourette Disease,Tourette Disorder,Tourette's Disease,Tourette's Disorder,Tourette's Syndrome,Syndrome, Tourette,Tourettes Disease,Tourettes Disorder,Tourettes Syndrome
D006239	Haplotypes	The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.	Haplotype
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000483	Alleles	Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.	Allelomorphs,Allele,Allelomorph