Physical Mapping, Linkage Analysis of a Putative Schizophrenia Locus on Chromosome 5q

Abstract

Two recent studies have suggested that a schizophrenia susceptibility locus may lie on the proximal long arm of chromosome 5. Partial trisomy of a 20-30 centimorgan region of chromosome 5 (5q11.2-13.3) was found to cosegregate with schizophrenia in a Canadian family of Chinese descent. Moreover, DNA markers from proximal 5q (D5S39, D5S76) were found to be linked to schizophrenia and related disorders in seven British and Icelandic families. We now report an initial physical map of DNA markers relative to the partial trisomy chromosome 5, as well as preliminary evidence against linkage of this region to schizophrenia in four American families.

Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree

“…Early reports from Bassatt et al [1988] and Sherrington et al [1988] suggested that loci on the long arm of chromosome 5 might be related to the expression of schizophrenia [Bassatt et al, 1988;Sherrington et al, 19881, although subsequent studies, including one from Sherrington et al [1988] could not confirm this [Kennedy et al, 1988;St. Clair et al, 1989;Hallmayer et al, 1992;Macciardi et al, 1992;Detera-Wadleigh et al, 1989;Aschauer et a]., 1990;McGuffin et al, 1990;Kaufman et al, 1989;Gurling, 19941. Overall, less attention has been focused on the short arm of chromosome 5, but while some studies have rejected linkage to various loci there [Kennedy et al, 1989;Coon et al, 19941, a carrier of a normal balanced chromosome 5 translocation (5: 141, including sections from both arms around the centromere (p14.1:q32.3), produced 5 offspring, 2 of whom had a partial 5p trisomy, one with schizophrenia the other with refractory epilepsy [Malaspina et al, 19921. We report evidence for linkage to the D 5 S l l l locus (5~14.1-p13.1) and other markers on the short arm of chromosome 5 in one large kindred, whose members were diagnosed using strictly defined predetermined criteria for the schizophrenia-related phenotype.…”

Linkage studies of schizophrenia: A simulation study of statistical power

“…Shemngton et al [1988], 15 from St. Claire et al[1989], 5 from Detera-Wadleigh et al[1989], 4 fromKaufmann et al [1989], 6 fromMcGuffin et al [1990], 7 fromAschauer et al [1990], and6 fromCroweeta1. [1991].…”

Molecular genetics of psychopathologies: A search for simple answers to complex problems

“…Subsequent studies (Kennedy et al, 1988;St. Clair et al, 1989;Detera-Wadleigh et al, 1989;Kaufman et aL, 1989;Aschauer et al, 1990;Crowe et al, 1990;McGuffin et al, 1990;Blackwood et aL, 1991a;Hallmayer et aL, 1992) in other families, however, have found no evidence for linkage of schizophrenia to the 5ql 1.2-q13.3 location.…”

“…For example, initial findings of linkage in studies of schizophrenia (Sherrington et al, 1988) and bipolar disorder (Egeland et al, 1987) have not been replicated in subsequent studies (Kennedy et al, 1988;St. Clair et al, 1989;Detera-Wadleigh et al, 1989;Kaufman et aL, 1989;Aschauer et al, 1990;Crowe et al, 1990;McGuffin et al, 1990;Blackwood et al, 1991a;Hallmayer et al, 1992).…”