TY - JOUR
T1 - Genetic diversity of the human serotonin receptor 1B (HTR1B)
AU - Sanders, A. R.
AU - Cao, Q.
AU - Taylor, J.
AU - Levin, T. E.
AU - Badner, J. A.
AU - Cravchik, A.
AU - Comeron, J. M.
AU - Naruya, S.
AU - Del Rosario, A.
AU - Salvi, D. A.
AU - Walczyk, K. A.
AU - Goldin, L. R.
AU - Mowry, B. J.
AU - Levinson, D. F.
AU - Crowe, R. R.
AU - Silverman, J. M.
AU - Gejman, P. V.
PY - 2000/8/7
Y1 - 2000/8/7
N2 - We extensively investigated polymorphisms in the coding and nearby non-coding regions of the intronless HTR1B, and their linkage disequilibrium relationships. By means of DGGE, database comparisons, and published assays, we have detected the following polymorphisms: G-511T, T-261G, -182INS/DEL-181, A-161T, C129T, T371G, T655C, C705T, G861C, A1099G, G1120A, and A1180G. The results of genotyping ten of these in an ethnic diversity panel (Pima/Jemez; Karatiana; Japanese; Chinese; Atayal; Indo-Pakistani; Middle Eastern; North of Sahara African; Mbutu/Biaka; Pacific Island; and European) revealed four common haplotypes: wild type, -182DEL-181, -161T, and 129T/861C. Gorilla and chimpanzee HTR1B sequence revealed the most common human alleles to be ancestral. One SNP, A-161T, had 108 transmissions of the A-161 allele to patients with schizophrenia versus 78 non-transmissions (nominal p=0.028). Nominal significance remained when linkage was controlled for by ASPEX/sib_tdt (p=0.041). Because many of the polymorphisms detected were uncommon, we also examined association of any variant allele with schizophrenia, which showed 222 transmissions versus 170 non-transmissions (nominal p=0.0086), and ASPEX/sib_tdt analysis (p=0.044). The expressed missense substitutions, T371G -> Phe124Cys, T655C -> Phe219Leu, A1099G -> Ile367Val, and G1120A -> Glu374Lys, could potentially affect ligand binding or interaction with G proteins, and thus modify drug response in carriers of these mutations.
AB - We extensively investigated polymorphisms in the coding and nearby non-coding regions of the intronless HTR1B, and their linkage disequilibrium relationships. By means of DGGE, database comparisons, and published assays, we have detected the following polymorphisms: G-511T, T-261G, -182INS/DEL-181, A-161T, C129T, T371G, T655C, C705T, G861C, A1099G, G1120A, and A1180G. The results of genotyping ten of these in an ethnic diversity panel (Pima/Jemez; Karatiana; Japanese; Chinese; Atayal; Indo-Pakistani; Middle Eastern; North of Sahara African; Mbutu/Biaka; Pacific Island; and European) revealed four common haplotypes: wild type, -182DEL-181, -161T, and 129T/861C. Gorilla and chimpanzee HTR1B sequence revealed the most common human alleles to be ancestral. One SNP, A-161T, had 108 transmissions of the A-161 allele to patients with schizophrenia versus 78 non-transmissions (nominal p=0.028). Nominal significance remained when linkage was controlled for by ASPEX/sib_tdt (p=0.041). Because many of the polymorphisms detected were uncommon, we also examined association of any variant allele with schizophrenia, which showed 222 transmissions versus 170 non-transmissions (nominal p=0.0086), and ASPEX/sib_tdt analysis (p=0.044). The expressed missense substitutions, T371G -> Phe124Cys, T655C -> Phe219Leu, A1099G -> Ile367Val, and G1120A -> Glu374Lys, could potentially affect ligand binding or interaction with G proteins, and thus modify drug response in carriers of these mutations.
UR - http://www.scopus.com/inward/record.url?scp=0006886806&partnerID=8YFLogxK
U2 - 10.1006/geno.2000.6411
DO - 10.1006/geno.2000.6411
M3 - Article
AN - SCOPUS:0006886806
SN - 1552-4841
VL - 96
SP - 564
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 4
ER -