Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region

Am J Med Genet B Neuropsychiatr Genet. 2005 May 5;135B(1):50-8. doi: 10.1002/ajmg.b.30165.


Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers D12S86 and D12S378 on chromosome 12 was the most probable genomic region to contain a susceptibility gene for affective disorders. Here we present a more detailed genetic analysis of a 7.7 Mb genomic region located on 12q24.31. This region was saturated with 20 microsatellite markers to refine the candidate region and linkage analysis performed in 41 families from the Saguenay-Lac-St-Jean (SLSJ) region of Quebec. The results of two point parametric analysis using MFLINK supported the presence of a susceptibility locus on chromosome 12q24.31. Association studies with microsatellite markers using a case/control sample from the same population (n = 401) and analyzed with CLUMP revealed significant allelic associations between the bipolar phenotype and markers NBG6 (P = 0.008) and NBG12 (P < 10(-3)). According to these results, we investigated candidate genes in the NBG12 area. We analyzed 32 genes for the presence of polymorphisms in coding sequences and intron/exon junctions and genotyped 22 non-synonymous SNPs in the SLSJ case/control sample. Two uncommon polymorphisms (minor allele frequency < or = 0.03) found in KIAA1595 and FLJ22471 genes, gave P-values below 0.05 with the T1 statistic. Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene. These results do not give strong support for a role in the susceptibility to bipolar disorder of any of these genes analyzed. However, the significance of rare polymorphisms should be explored by further analyses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Bipolar Disorder / genetics*
  • Chromatography, High Pressure Liquid / methods
  • Chromosomes, Human, Pair 12 / genetics*
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Gene Frequency
  • Genetic Linkage
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Microsatellite Repeats / genetics*
  • Polymorphism, Single Nucleotide*


  • DNA