Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia

Abstract

Cytogenetic analysis was carried out in unrelated schizophrenic patients, unrelated controls and patients and family members in multiplex families. The size distribution of chromosome 1 heterochromatic region (1qH, C-band variants) among 21 unrelated schizophrenic patients was different from that found in a group of 46 controls. The patient group had 1qH variants of smaller size than the control group (P < 0.01). Incubation of phytohemagglutinin-treated blood lymphocytes with 5-azacytidine (which causes decondensation and extension of the heterochromatin) led to a lesser degree of heterochromatin decondensation in a group of patients than in the controls (7 schizophrenic, 9 controls, P < 0.01). The distribution of phenotypes of Duffy blood group system [whose locus is linked to the 1qH region (Donahue et al.: Proc Natl Acad Sci USA 61:949-955, 1968; Rouleau et al.: Genomics 7:313-318, 1990)] among 28 schizophrenic patients was also different from that in the general population. Cosegregation of schizophrenia with a 1qH (C-band) variant and Duffy blood group allele was observed in one of six multiplex families. The overall results suggest that alterations within the Duffy/1qH region are involved in schizophrenia in some cases. This region contains the locus of D5 dopamine receptor pseudogene 2 (1q21.1), which is transcribed in normal lymphocytes (Takahashi et al.: FEBS Lett 314:23-25, 1992).

Linkage of schizophrenia with chromosome 1q loci in Taiwanese families

“…These linkage findings justify further positional cloning studies to identify the vulnerability gene in the 1q22-31 region. Several studies had reported encouraging findings of an association of several vulnerability genes in this region with schizophrenia, such as a potassium channel gene [KCNN3], 44 a fragile site, 45 a heterochromatin variant, 46 and the Duffy blood group. 47 The chromosome region 1q41-44 covered by the markers of D1S320, D1S251, D1S404, D1S2836, and D1S180 with positive NPL scores covered a distance of 26.8 cM, especially in the broad phenotype model.…”

Failure to confirm genetic association between schizophrenia and markers on chromosome 1q23.3 in the region of the gene encoding the regulator of G‐protein signaling 4 protein (RGS4)

“…Subsequently two linkage studies found significant evidence for linkage at 1q23.3, which is centromeric to the locus implicated by a cytogenetic abnormality [Brzustowicz et al, 2000;Gurling et al, 2001]. Another study combined allelic association, cytogenetic and family linkage data on chromosome 1 using heterochromatic C-band variants in the q22.1-23 region and found cosegregation of a 1qH (C-band) variant and Duffy blood group alleles with schizophrenia in a single family [Kosower et al, 1995]. Other linkage studies from Finland found significant evidence for linkage to schizophrenia in a position that was telomeric to 1q23.3 but proximal to 1q42.1 [Ekelund et al, 1997[Ekelund et al, , 2000Hovatta et al, 1999].…”

Mapping of hKCa3 to chromosome 1q21 and investigation of linkage of CAG repeat polymorphism to schizophrenia

“…5 The 1q21 region has been linked to familial hemiplegic migraine 16,17 but not to schizophrenia or any other neuropsychiatric disorder, 18,19 though variations in heterochromatin in the 1q21 region have been reported in schizophrenics. 20 Independent of the gene's map location, the observation of association between longer-CAG hKCa3 repeat alleles and schizophrenia was important, so we investigated hKCa3 repeat lengths in the population of the National Insitute of Mental Health (NIHM) Schizophrenia Genetics Initiative. This dataset is made up of extended families, with members both affected and unaffected with schizophrenia.…”