Genetic diversity of the human serotonin receptor 1B (HTR1B) gene.
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.
Schizophrenia Genetics Research Program, The University of Chicago, Chicago, Illinois 60637, USA.
A R
AR
Sanders
Q
Q
Cao
J
J
Taylor
T E
TE
Levin
J A
JA
Badner
A
A
Cravchik
J M
JM
Comeron
S
S
Naruya
A
A
Del Rosario
D A
DA
Salvi
K A
KA
Walczyk
B J
BJ
Mowry
D F
DF
Levinson
R R
RR
Crowe
J M
JM
Silverman
P V
PV
Gejman
D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016208:Databases, Factual; D004586:Electrophoresis; D005006:Ethnicity / Q000235:genetics; D019143:Evolution, Molecular; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000737:chemistry / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D017422:Sequence Analysis, DNA
D005819:Genetic Markers; C470302:HTR1B protein, human; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin