Exclusion of close linkage of the dopamine transporter gene with schizophrenia spectrum disorders.
OBJECTIVE
Involvement of genetic factors in the pathogenesis of schizophrenia spectrum disorders has been indicated in twin, adoption, and familial aggregation studies; the pivotal role played by the dopamine transporter in dopaminergic neurotransmission makes it a candidate gene for these disorders. Detection of close linkage between a dopamine transporter marker and schizophrenia spectrum disorders would strongly support the existence of causal relationships between genetic mutations at the dopamine transporter locus and the disease phenotype.


METHODS
The authors assessed the linkage between this gene and schizophrenia spectrum disorders by using polymorphic dopamine transporter gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia as well as schizophreniform, schizoaffective, and schizotypal disorders and mood-incongruent psychotic depression.


RESULTS
Complete (theta = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models.


CONCLUSIONS
These results indicate that allelic variants at the dopamine transporter locus do not provide major genetic contributions to the etiology of schizophrenia and related disorders in these pedigrees.
Persico
A M
AM
From the Molecular Neurobiology Branch, National Institute on Drug Abuse/NIH, Baltimore, MD 21224.
Wang
Z W
ZW
Black
D W
DW
Andreasen
N C
NC
Uhl
G R
GR
Crowe
R R
RR
D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010375:Pedigree; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins