title: Haplotype co-segregation with attention deficit-hyperactivity disorder in unrelated German multi-generation families.
abstract: Complex disorders have proved to be elusive in the search for underlying genetic causes. In the presence of large multi-generation pedigrees with multiple affected individuals, heritable familial forms of the disorders can be postulated. Observations of particular chromosomal haplotypes shared among all affected individuals within pedigrees may reveal chromosomal regions, in which the disease-related genes may be located. Hence, the biochemical pathways involved in pathogenesis can be exposed. We have recruited eight large Attention Deficit-Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent. Densely spaced informative microsatellite markers with high heterozygosity rates were used to fine-map and haplotype chromosomal regions of interest in these families. In three subsets and one full family of the eight ADHD families, haplotypes co-segregating with ADHD-affected individuals were identified at chromosomes 1q25, 5q11-5q13, 9q31-9q32, and 18q11-18q21. Positive LOD scores supported these co-segregations. The existence of haplotypes co-segregating among affected individuals in large ADHD pedigrees suggests the existence of Mendelian forms of the disorder and that ADHD-related genes are located within these haplotypes. In depth sequencing of these haplotype regions can identify causative genetic mechanisms and will allow further insights into the clinico-genetics of this complex disorder.
authors.affiliation: Department of Neurobehavioral Genetics, University of Trier, Institute of Psychobiology, Trier, Germany.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Lin
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Schote
authors.forename: Haukur
authors.initials: H
authors.lastname: Pálmason
authors.forename: Christiane
authors.initials: C
authors.lastname: Seitz
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Renner
authors.forename: Marcel
authors.initials: M
authors.lastname: Romanos
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.forename: Christian P
authors.initials: CP
authors.lastname: Jacob
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Jobst
authors.initials: J
authors.lastname: Meyer
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D005191:Family Characteristics; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D005858:Germany; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic
keywords: ADHD; Mendelian; co-segregation; haplotypes