Chromosomes 4 5 12 and

Among the other autosomal DNA markers of interest are findings for chromosome 4, 5, 12, and 21 markers. Blackwood et al.(35) reported linkage between a locus on chromosome 4p (D4S394, 4p16) and bipolar affective disorder in a large family. Dopamine D 5 receptor gene and the a2C-adrenergic receptor gene are located in the same region. Major candidate genes for the affective disorders are located on chromosome 5. Preliminary linkage data including three DNA markers on this chromosome (D5S39, D5S43, and D5S62) suggested linkage with bipolar affective disorder.(36) Two of these markers (D5S62 and D5S43) are located in the distal region of the long arm of chromosome 5 (5q35-q ter) and contain candidate genes contributing to the neurotransmitter receptors for dopamine, noradrenaline

(norepinephrine), glutamate, and g-aminobutyric acid. These two markers, however, had exclusion lod scores in a previous study of 14 families. Dopamine transporter gene (DAT1) is located in a different region of chromosome 5 (5p15). This marker has been investigated in an association study with bipolar affective disorder yet no association was found.(38) Kelsoe et al/39.) recently reported a possible linkage between a locus near the dopamine transporter (DAT) locus on chromosome 5 and bipolar affective disorder.

The Darier's disease region on chromosome 12q23-q24.1 has been investigated in several family studies in bipolar affective disorder, suggesting a possible linkage/4 d1.,42 and 43> Two of these studies have been able to report significant lod scores greater than 3.(4 43> To further test the hypothesis that genes containing expanded trinucleotide repeats may contribute to the genetic aetiology of bipolar affective disorder, loci within this region containing CAG/CTG repeat expansions have also been investigated, but no association was found with bipolar affective disorder. (44)

Straub et al.(45> detected linkage with the 21q22.3 locus on chromosome 21 in one bipolar family. Overall, however, the 47 families assessed for this genome do not support linkage with this marker.

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