Absence of Linkage of Apparently Single Gene Mediated ADHD With the Human Syntenic

up to 8% of the general population and often impairs social, academic, and job perfor- mance. 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 re- sponsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (2Opll-p12). Five families in which the pat- tern of inheritance of ADHD appears to be autosomal dominant were studied. Segrega- tion analysis of the traits studied suggested that the best fitting model was a sex-influ- enced, single gene, Mendelian pattern. Sev- eral genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our pa- tient population and those of other investi- gators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval.