quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fl...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-10, Vol.104 (40), p.15811-15816
Main Authors: Freimer, Nelson B, Service, Susan K, Ophoff, Roel A, Jasinska, Anna J, McKee, Kevin, Villeneuve, Amelie, Belisle, Alexandre, Bailey, Julia N, Breidenthal, Sherry E, Jorgensen, Matthew J, Mann, J. John, Cantor, Rita M, Dewar, Ken, Fairbanks, Lynn A
Format: Article
Language:English
Subjects:
Age
Animals
Base Sequence
Biological Sciences
Dopamine - cerebrospinal fluid
Dopamine - metabolism
Female
Genetic loci
Genetic mapping
Genetic research
Genetic Variation
Genome
Genomes
Genomics
Heritability
Homovanillic Acid - metabolism
Human genetics
Hydroxyindoleacetic Acid - cerebrospinal fluid
Hydroxyindoleacetic Acid - metabolism
Macaca mulatta
Male
Medical genetics
Metabolism
Models, Animal
Nervous system
Neurotransmitters
Personality traits
Phenotypic traits
Polymorphism, Single Nucleotide
Primates
Quantitative Trait Loci
Species Specificity
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Summary:Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0707640104