TY - JOUR
T1 - Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia
AU - Pedrosa, Erika
AU - Stefanescu, Radu
AU - Margolis, Benjamin
AU - Petruolo, Oriana
AU - Lo, Yungtai
AU - Nolan, Karen
AU - Novak, Tomas
AU - Stopkova, Pavla
AU - Lachman, Herbert M.
PY - 2008/7
Y1 - 2008/7
N2 - Cadherins and protocadherins are cell adhesion proteins that play an important role in neuronal migration, differentiation and synaptogenesis, properties that make them targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Consequently, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider. One such set of candidate genes is the 5q31-linked PCDH family, which consists of more than 50 exons encoding three related, though distinct family members - α, β, and γ - which can generate thousands of different protocadherin proteins through alternative promoter usage and cis-alternative splicing. In this study, we focused on a SNP, rs31745, which is located in a putative PCDHα enhancer mapped by ChIP-chip using antibodies to covalently modified histone H3. A striking increase in homozygotes for the minor allele at this locus was detected in patients with BD. Molecular analysis revealed that the SNP causes allele-specific changes in binding to a brain protein. The findings suggest that the 5q31-linked PCDH locus should be more thoroughly considered as a disease-susceptibility locus in psychiatric disorders.
AB - Cadherins and protocadherins are cell adhesion proteins that play an important role in neuronal migration, differentiation and synaptogenesis, properties that make them targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Consequently, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider. One such set of candidate genes is the 5q31-linked PCDH family, which consists of more than 50 exons encoding three related, though distinct family members - α, β, and γ - which can generate thousands of different protocadherin proteins through alternative promoter usage and cis-alternative splicing. In this study, we focused on a SNP, rs31745, which is located in a putative PCDHα enhancer mapped by ChIP-chip using antibodies to covalently modified histone H3. A striking increase in homozygotes for the minor allele at this locus was detected in patients with BD. Molecular analysis revealed that the SNP causes allele-specific changes in binding to a brain protein. The findings suggest that the 5q31-linked PCDH locus should be more thoroughly considered as a disease-susceptibility locus in psychiatric disorders.
KW - Bipolar disorder
KW - Cadherin schizophrenia
KW - Chromatin
KW - Protocadherin
UR - http://www.scopus.com/inward/record.url?scp=46249106282&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46249106282&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2008.04.013
DO - 10.1016/j.schres.2008.04.013
M3 - Article
C2 - 18508241
AN - SCOPUS:46249106282
SN - 0920-9964
VL - 102
SP - 210
EP - 219
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -