Neurogenetics

, Volume 4, Issue 1, pp 43–53

A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family

  • Bora E. Baysal
  • Joan E. Willett-Brozick
  • Judith A. Badner
  • Winston Corona
  • Robert E. Ferrell
  • Vishwajit L. Nimgaonkar
  • Sevilla D. Detera-Wadleigh
Original Article

Abstract

Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The inborn errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intra-genic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed.

Protein glycosylation Glycan Single nucleotide polymorphism Molecular evolution Complex genetic disorder 

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Bora E. Baysal
    • 1
  • Joan E. Willett-Brozick
    • 1
  • Judith A. Badner
    • 4
  • Winston Corona
    • 5
  • Robert E. Ferrell
    • 3
  • Vishwajit L. Nimgaonkar
    • 1
  • Sevilla D. Detera-Wadleigh
    • 5
  1. 1.Department of Psychiatry, The University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaUSA
  2. 2.Department of Otolaryngology, The University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaUSA
  3. 3.Department of Human Genetics, The University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaUSA
  4. 4.Department of Psychiatry, University of Chicago, Chicago, IllinoisUSA
  5. 5.National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MarylandUSA
  6. 6.University of Pittsburgh School of Medicine, 3811 O'Hara Street R1445, Pittsburgh, PA 15213USA

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