Genetic Diversity of the Human Serotonin Receptor 1B (HTR1B) Gene

• Published in: Genomics (San Diego, Calif.) Vol. 72; no. 1; pp. 1 - 14
• Main Authors: Sanders, Alan R., Cao, Qiuhe, Taylor, Jennifer, Levin, Tamara E., Badner, Judith A., Cravchik, Anibal, Comeron, Josep M., Naruya, Saitou, Del Rosario, Amado, Salvi, Debra A., Walczyk, Katherine A., Mowry, Bryan J., Levinson, Douglas F., Crowe, Raymond R., Silverman, Jeremy M., Gejman, Pablo V.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.02.2001; Elsevier
• Subjects: Alleles; Amino Acid Sequence; Amino Acid Substitution; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; Continental Population Groups - genetics; Databases, Factual; Electrophoresis; Ethnic Groups - genetics; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; HTR1B gene; Human; Humans; Linkage Disequilibrium; Molecular Sequence Data; Nucleic Acid Conformation; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin - chemistry; Receptors, Serotonin - genetics; RNA, Messenger - chemistry; RNA, Messenger - genetics; Schizophrenia - genetics; Sequence Analysis, DNA; Psychosis; Human; Molecular evolution; Serotonin; Family study; Schizophrenia; Genetic diversity; Serotonine receptor; Linkage equilibrium; Polymorphism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2000.6411

We systematically and comprehensively investigated polymorphisms of the HTR1B 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 published assays: G-511T, T-261G, –182INS/DEL-181, A-161T, C129T, T371G, T655C, C705T, G861C, A1099G, G1120A, and A1180G. The results of the intermarker analyses showed strong linkage disequilibrium between the C129T and the G861C polymorphisms and revealed four common haplotypes: ancestral (via chimpanzee comparisons), 129T/861C, -161T, and -182DEL-181. The results of association tests with schizophrenia were negative, although A-161T had a nominal P = 0.04 via ASPEX/sib_tdt. The expressed missense substitutions, Phe124Cys, Phe219Leu, Ile367Val, and Glu374Lys, could potentially affect ligand binding or interaction with G proteins and thus modify drug response in carriers of these variants. On average, the human cSNPs and differences among other 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.