Genetic diversity of the human serotonin receptor 1B (HTR1B) gene

We systematically and comprehensively investigated polymorphisms of the HTR 1B gene as well as their linkage disequilibrium and ancestral relationships . We have detected the following polymorphisms in our sample via denaturing gradient gel electrophoresis, database comparisons, and/or previously publ ished assays: G-511T, T-261G, -182INS/DEL-181, A-161T, C129T, T371G, T655C, C705T, G861C, A1099G, G1120A, and A1180G. The results of the intermarker a nalyses showed strong linkage disequilibrium between the C129T and the G861 C polymorphisms and revealed four common haplotypes: ancestral (via chimpan zee comparisons), 129T/861C, -161T, and -182DEL-181. The results of associa tion tests with schizophrenia were negative, although A-161T had a nominal P = 0.04 via AS-PEX/sib_tdt. The expressed missense substitutions, Phe124Cy s, Phe219Leu, Ile367Val, and Glu374Lys, could potentially affect ligand bin ding or interaction with G proteins and thus modify drug response in carrie rs of these variants. On average, the human cSNPs and differences among oth er primates clustered in the more thermodynamically unstable regions of the mRNA, which suggests that the evolutionary survival of nucleotide sequence variation may be influenced by the mRNA structure of this gene, (C) 2001 A cademic Press.