A novel CpG-associated brain-expressed candidate gene for chromosome 18q-linked bipolar disorder

Mol Psychiatry. 2003 Jan;8(1):83-9. doi: 10.1038/sj.mp.4001190.

Abstract

We previously identified 18q21-q22 as a candidate region for bipolar (BP) disorder and constructed a yeast artificial chromosome (YAC) contig map. Here we identified three potential CpG islands using CCG/CGG YAC fragmentation. Analysis of available genomic sequences using bioinformatic tools identified an exon of 3639 bp downstream of a CpG island of 1.2 kb containing a putative transcription initiation site. The exon contained an open reading frame coding for 1212 amino acids with significant homology to the SART-2 protein; weaker homology was found with a series of sulphotransferases. Alignment of cDNA sequences of corresponding ESTs and RT-PCR sequencing predicted a transcript of 9.5 kb which was confirmed by Northern blot analysis. The transcript was expressed in different brain areas as well as in multiple other peripheral tissues. We performed an extensive mutation analysis in 113 BP patients. A total of nine single nucleotide polymorphisms (SNPs) were identified. Five SNPs predicted an amino acid change, of which two were present in BP patients but not in 163 control individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Antigens, Neoplasm / genetics
  • Bipolar Disorder / genetics*
  • Chromosomes, Artificial, Yeast
  • Chromosomes, Human, Pair 18*
  • CpG Islands / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Gene Expression
  • Humans
  • Neoplasm Proteins / genetics
  • Open Reading Frames / genetics
  • Polymorphism, Single Nucleotide
  • Trinucleotide Repeat Expansion

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • DSE protein, human