TY - JOUR
T1 - Analysis of the pseudoautosomal X-linked gene SYBL1 in bipolar affective disorder
T2 - Description of a new candidate allele for psychiatric disorders
AU - Saito, Takuya
AU - Parsia, Sam
AU - Papolos, Demitri F.
AU - Lachman, Herbert M.
PY - 2000/6/12
Y1 - 2000/6/12
N2 - The absence of father-to-son transmission has been observed in a subset of families with bipolar disorder (BPD), suggestive of a susceptibility gene on the sex-linked portion of the X chromosome. This is supported by some genetic linkage studies that have provided evidence for a susceptibility locus near Xq28. We have analyzed one candidate gene on Xq28, SYBL1, which maps to the Xq pseudoautosomal region (PAR). SYBL1 encodes a member of the synaptobrevin family of proteins that is involved in synaptic vesicle docking and membrane transport. Genes in the PAR generally escape X chromosome inactivation and have an active homolog on the Y chromosome, which would result in an increase in same-sex concordance in paternal transmitted traits. However, SYBL1 is neither expressed on the Y chromosome nor the inactive X chromosome and would therefore be expected to show typical sex-linked transmission. We have screened SYBL1 for mutations that could be tested as candidate alleles in the development of BPD. Following single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, four single nucleotide polymorphisms were detected: a silent mutation at codon 108, two intron mutations without any obvious biological significance, and a G→C transversion in the polypyrimidine tract at the 3' splice acceptor site preceding exon 8. This polymorphism, which creates a perfect 16/16 stretch of pyrimidines, was analyzed in 110 patients with BPD not selected for sex- linked transmission and 119 control subjects. The results show a statistical trend toward an increase in the frequency of the C allele in males with BPD but not females. Males: χ2 = 3.46, 1 df, p = .06; Females: χ2 = .20, 1 df, p = .66. (C) 2000 Wiley-Liss, Inc.
AB - The absence of father-to-son transmission has been observed in a subset of families with bipolar disorder (BPD), suggestive of a susceptibility gene on the sex-linked portion of the X chromosome. This is supported by some genetic linkage studies that have provided evidence for a susceptibility locus near Xq28. We have analyzed one candidate gene on Xq28, SYBL1, which maps to the Xq pseudoautosomal region (PAR). SYBL1 encodes a member of the synaptobrevin family of proteins that is involved in synaptic vesicle docking and membrane transport. Genes in the PAR generally escape X chromosome inactivation and have an active homolog on the Y chromosome, which would result in an increase in same-sex concordance in paternal transmitted traits. However, SYBL1 is neither expressed on the Y chromosome nor the inactive X chromosome and would therefore be expected to show typical sex-linked transmission. We have screened SYBL1 for mutations that could be tested as candidate alleles in the development of BPD. Following single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, four single nucleotide polymorphisms were detected: a silent mutation at codon 108, two intron mutations without any obvious biological significance, and a G→C transversion in the polypyrimidine tract at the 3' splice acceptor site preceding exon 8. This polymorphism, which creates a perfect 16/16 stretch of pyrimidines, was analyzed in 110 patients with BPD not selected for sex- linked transmission and 119 control subjects. The results show a statistical trend toward an increase in the frequency of the C allele in males with BPD but not females. Males: χ2 = 3.46, 1 df, p = .06; Females: χ2 = .20, 1 df, p = .66. (C) 2000 Wiley-Liss, Inc.
KW - Attention deficit hyperactivity disorder (ADHD)
KW - Handedness
KW - Laterality
KW - Manic depressive illness
KW - Schizophrenia
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U2 - 10.1002/1096-8628(20000612)96:3<317::AID-AJMG17>3.0.CO;2-R
DO - 10.1002/1096-8628(20000612)96:3<317::AID-AJMG17>3.0.CO;2-R
M3 - Article
C2 - 10898908
AN - SCOPUS:0034640678
SN - 1552-4841
VL - 96
SP - 317
EP - 323
JO - American Journal of Medical Genetics - Neuropsychiatric Genetics
JF - American Journal of Medical Genetics - Neuropsychiatric Genetics
IS - 3
ER -