1Nature 2004 Apr 428: 522-8
TitleThe DNA sequence and analysis of human chromosome 13.
AbstractChromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.
SCZ Keywordsschizophrenia
2Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Oct 153B: 1276-82
TitleAssociation analysis of PALB2 and BRCA2 in bipolar disorder and schizophrenia in a scandinavian case-control sample.
AbstractA recent genome-wide association study (GWAS) found significant association between the PALB2 SNP rs420259 and bipolar disorder (BD). The intracellular functions of the expressed proteins from the breast cancer risk genes PALB2 and BRCA2 are closely related. Therefore, we investigated the relation between genetic variants in PALB2 and BRCA2 and BD. Due to increasing evidence of genetic overlap between BD and schizophrenia (SCZ), we also investigated association with SCZ. In a Scandinavian case-control sample (n?=?686/2,538) we found the BRCA2 SNP rs9567552 to be significantly associated with BD (Nominal P?=?0.00043). Additionally, we replicated the association between PALB2 SNP rs420259 and BD (Nominal P?=?0.025). We then combined our sample with another Nordic case-control sample (n?=?435/11,491) from Iceland, and added results from the Wellcome Trust Case Control Consortium (WTCCC) (n?=?1,868/2,938) and the STEP-UCL/ED-DUB-STEP2 study (n?=?2,558/3,274) in a meta-analysis which revealed a P-value of 1.2??10(-5) for association between PALB2 SNP rs420259 and BD (n?=?5,547/20,241). Neither the PALB2 SNP rs420259 nor the BRCA2 SNP rs9567552 were nominally significantly associated with the SCZ phenotype in our Scandinavian sample (n?=?781/2,839). Our findings support PALB2 and BRCA2 as risk genes specifically for BD, and suggest that altered DNA repair related to neurogenesis may be involved in BD pathophysiology. 2010 Wiley-Liss, Inc.
SCZ Keywordsschizophrenia