title: Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutant Coloboma.
abstract: Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex-influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval.
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Hess
authors.forename: P K
authors.initials: PK
authors.lastname: Rogan
authors.forename: M
authors.initials: M
authors.lastname: Domoto
authors.forename: D E
authors.initials: DE
authors.lastname: Tinker
authors.forename: R L
authors.initials: RL
authors.lastname: Ladda
authors.forename: J C
authors.initials: JC
authors.lastname: Ramer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D008875:Middle Aged; D015233:Models, Statistical; D010375:Pedigree