TY - JOUR
T1 - Genetic diversity of the human serotonin receptor 1B (HTR1B) gene
AU - Sanders, Alan R.
AU - Cao, Qiuhe
AU - Taylor, Jennifer
AU - Levin, Tamara E.
AU - Badner, Judith A.
AU - Cravchik, Anibal
AU - Comeron, Josep M.
AU - Naruya, Saitou
AU - Del Rosario, Amado
AU - Salvi, Debra A.
AU - Walczyk, Katherine A.
AU - Mowry, Bryan J.
AU - Levinson, Douglas F.
AU - Crowe, Raymond R.
AU - Silverman, Jeremy M.
AU - Gejman, Pablo V.
N1 - Funding Information:
We thank the families who participated in these studies and the many individuals who helped to advance this work, especially Elliot S. Gershon, M.D. This research was partially supported by both the Division of Intramural Research Programs of the National Institute of Mental Health and the Department of Psychiatry of the University of Chicago.
PY - 2001/2/15
Y1 - 2001/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035864896&partnerID=8YFLogxK
U2 - 10.1006/geno.2000.6411
DO - 10.1006/geno.2000.6411
M3 - Article
C2 - 11247661
AN - SCOPUS:0035864896
SN - 0888-7543
VL - 72
SP - 1
EP - 14
JO - Genomics
JF - Genomics
IS - 1
ER -