Alternative transcripts and evidence of imprinting of GNAL on 18p11.2.
Genetic studies implicating the region of human chromosome 18p11.2 in susceptibility to bipolar disorder and schizophrenia have observed parent-of-origin effects that may be explained by genomic imprinting. We have identified a transcriptional variant of the GNAL gene in this region, employing an alternative first exon that is 5' to the originally identified start site. This alternative GNAL transcript encodes a longer functional variant of the stimulatory G-protein alpha subunit, Golf. The isoforms of Golf display different expression patterns in the CNS and functionally couple to the dopamine D1 receptor when heterologously expressed in Sf9 cells. In addition, there are CpG islands in the vicinity of both first exons that are differentially methylated, a hallmark of genomic imprinting. These results suggest that GNAL, and possibly other genes in the region, is subject to epigenetic regulation and strengthen the case for a susceptibility gene in this region.
Corradi
J P
JP
Department of Target Biology, AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
Ravyn
V
V
Robbins
A K
AK
Hagan
K W
KW
Peters
M F
MF
Bostwick
R
R
Buono
R J
RJ
Berrettini
W H
WH
Furlong
S T
ST
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics*; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D018076:DNA, Complementary / Q000235:genetics; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D018411:Spodoptera; D014158:Transcription, Genetic
D018076:DNA, Complementary; D044385:GTP-Binding Protein alpha Subunits; D011994:Recombinant Proteins; C084618:olfactory G protein subunit alpha olf