We have determined the genomic structure of the human glucocorticoid receptor (hGR) which includes exon/intron organization, sequences around the splice Junctions, the promoter sequence, transcription start site and the alternative splice sites on the 3' end that give rise to the alpha and beta forms of the receptor. The gene contains a total of ten exons and is at least 80 kb. Each receptor isoform is encoded by nine exons. The ninth exon is heterologous. A preponderance of GC is evident on the putative promoter region of the gene. The transcription start site is localized to the *C within TAC*CCTC. By alignment of sequences around the splice junctions of hGR with other receptors in the superfamily, three difference splice positions within the DNA binding domain are observed, suggesting early evolutionary divergence of the ancestral gene into at least three different branches corresponding to ligand type. The comparison also permitted prediction of the positions of nine of these sites and sizes of the putative exons in the human mineralocorticoid receptor (hMR). By sequence analysis we have confirmed the presence of alpha-satellite repeats in an hGR cosmid which we initially found by fluorescent in situ hybridization. Systematic genomic mapping for a bipolar illness locus has been initiated using twenty genetically mapped markers on chromosome 5 in 13 affected pedigrees. We have used 5 probes on 11p. In addition, 11 probes mapping to chromosome 2 have been tested as well as two probes on 10p. Since chromosome 2 is at least 320 cM in recombination size, more markers are being studied. So far we have not found any evidence for linkage.
| Dick, Danielle M; Foroud, Tatiana; Flury, Leah et al. (2003) Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Am J Hum Genet 73:107-14 |
