Prominent findings with markers in the pericentromeric region of chromosome 18 have been recently published. Berrettini et al. (27> first reported linkage of bipolar affective disorder to chromosome 18 DNA markers in a systematic genome survey including 22 families. These authors' results suggest that a susceptibility gene is present in the pericentromeric region of this chromosome. Results of linkage analysis in individual families indicated possible linkage with some marker loci in this region (18p11). This result is of considerable interest, both because of its significance and also because it is at this location that one finds genes coding for the a unit of a guanosine triphosphate binding protein involved in neurotransmission and the corticotrophin receptor gene. Stine et al.2) studied 28 nuclear families for markers on chromosome 18 and also found evidence for linkage with bipolar affective disorder. This study also demonstrated evidence of a parent-of-origin effect operating in bipolar affective disorder (an excess of paternally but not maternally transmitted alleles). Gershon et al.,(29 on the other hand, observed linkage with chromosome 18 markers in affected sib-pair analysis only in pedigrees with mixed paternal-maternal transmission. Linkage was not found in pedigrees with exclusively maternal transmission. Chromosome 18 markers have been investigated in two large Belgian pedigrees with bipolar affective disorder. (39 Negative lod scores were found for a marker located in the pericentromeric region. Linkage and segregation analysis in one family suggested that a different region of chromosome 18 (18q21.33-q23) may contain a susceptibility locus for bipolar affective disorder. Freimer et al.(3!) used both linkage and association strategies and also reported evidence of linkage with markers in this region (18q23). Despite slight allele sharing with two markers on chromosome 18 (D18S40 on 18p and D18S70 on 18q) in the National Institute of Mental Health genetics initiative bipolar affective disorder pedigrees, (32) these results were not confirmed in this large genome scan. A negative lod score was found for D18S40 in the study of De Bruyn et al.(30) on 18p markers, indicating exclusion of this region.

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