A Linkage Study of Chromosome 11q in Schizophrenia

Abstract

The long arm of chromosome 11 is of interest in schizophrenia research because of three independent reports of balanced 11q translocations cosegregating with schizophrenia and other major psychiatric illness in pedigrees. In addition, a number of candidate genes for psychosis are located in the translocated regions. These include the dopamine D2 receptor, porphobilinogen deaminase, which has shown an allelic association with schizophrenia, and neural cell adhesion molecule, a cell surface glycoprotein involved in neuronal cell-cell recognition during brain development. To search for a schizophrenia locus on chromosome 11q, we conducted linkage analyses in 12 multiplex pedigrees. Sixteen DNA markers, including the above three candidate genes, were used to screen the entire long arm of chromosome 11. None of these markers were supportive of linkage to schizophrenia regardless of whether the affected phenotype was defined narrowly or broadly, whether high or low penetrance was assumed. Both dominant and recessive models tested more than 130 centimorgans of chromosome 11q, and therefore, the reported translocation regions. The results provide no evidence for a susceptibility locus for schizophrenia on chromosome 11q in these pedigrees.

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

“…[87][88][89][90][91][92][93][94][95] A recent large genome-wide scan emphasized the weakness and fragility of linkage reports in schizophrenia, as no linkage appears to be consistently replicable across large studies. 96 The data suggest some positive findings on chromosome 2, 10, and 22 96 as well as X-chromosome findings 97 and thus require additional investigation.…”

The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia

“…Other linkage studies have in contrast yielded negative results. 22,23 The previous failure to find linkage in the region of the GRM5 gene may be related to the small effect size seen in this study and illustrates the power of the association approach for such susceptibility loci. A more extensive survey in different cohorts and populations, to determine whether the 197-bp allele is found exclusively in 'at risk' individuals, is now warranted.…”

Some Capabilities for Model-Based and Model-Free Linkage Analysis using the Program Package S.A.G.E. (Statistical Analysis for Genetic Epidemiology)

“…Previous studies have found linkage to chromosome 8 for these data [23] . Other studies have previously reported findings suggesting the importance of chromosome 11 [24][25][26][27][28][29] and chromosome 13 [30][31][32][33] , and a recent meta-analysis found evidence for linkage to 1, 2q, 3q, 4q, 5q, 8p and 10q [34] . We therefore believe our analysis of susceptibility has probably increased the power of linkage analysis in these data.…”