SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region

Donna J E Housley, Molly Nikolas, Patrick J. Venta, Kathrine A. Jernigan, Irwin D. Waldman, Joel Nigg, Karen H. Friderici

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The dopamine receptor 5 gene (DRD5) holds much promise as a candidate locus for contributing to neuropsychiatric disorders and other diseases influenced by the dopaminergic system, as well as having potential to affect normal behavioral variation. However, detailed analyses of this gene have been complicated by its location within a segmentally duplicated chromosomal region. Microsatellites and SNPs upstream from the coding region have been used for association studies, but we find, using bioinformatics resources, that these markers all lie within a previously unrecognized second segmental duplication (SD). In order to accurately analyze the DRD5 locus for polymorphisms in the absence of contaminating pseudogene sequences, we developed a fast and reliable method for sequence analysis and genotyping within the DRD5 coding region. We employed restriction enzyme digestion of genomic DNA to eliminate the pseudogenes prior to PCR amplification of the functional gene. This approach allowed us to determine the DRD5 haplotype structure using 31 trios and to reveal additional rare variants in 171 unrelated individuals. We clarify the inconsistencies and errors of the recorded SNPs in dbSNP and HapMap and illustrate the importance of using caution when choosing SNPs in regions of suspected duplications. The simple and relatively inexpensive method presented herein allows for convenient analysis of sequence variation in DRD5 and can be easily adapted to other duplicated genomic regions in order to obtain good quality sequence data.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalAnnals of Human Genetics
Volume73
Issue number3
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Haplotypes
Single Nucleotide Polymorphism
Pseudogenes
Sequence Analysis
Genomic Segmental Duplications
HapMap Project
Gene Amplification
Dopamine Receptors
Computational Biology
Microsatellite Repeats
Genes
Digestion
Polymerase Chain Reaction
DNA
Enzymes
Data Accuracy

Keywords

  • ADHD
  • Behavior
  • Dopamine receptor
  • Genomicre arrangement
  • Paralogous sequence variant
  • Segmental duplication

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Housley, D. J. E., Nikolas, M., Venta, P. J., Jernigan, K. A., Waldman, I. D., Nigg, J., & Friderici, K. H. (2009). SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region. Annals of Human Genetics, 73(3), 274-282. https://doi.org/10.1111/j.1469-1809.2009.00513.x

SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region. / Housley, Donna J E; Nikolas, Molly; Venta, Patrick J.; Jernigan, Kathrine A.; Waldman, Irwin D.; Nigg, Joel; Friderici, Karen H.

In: Annals of Human Genetics, Vol. 73, No. 3, 2009, p. 274-282.

Research output: Contribution to journalArticle

Housley, DJE, Nikolas, M, Venta, PJ, Jernigan, KA, Waldman, ID, Nigg, J & Friderici, KH 2009, 'SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region', Annals of Human Genetics, vol. 73, no. 3, pp. 274-282. https://doi.org/10.1111/j.1469-1809.2009.00513.x
Housley, Donna J E ; Nikolas, Molly ; Venta, Patrick J. ; Jernigan, Kathrine A. ; Waldman, Irwin D. ; Nigg, Joel ; Friderici, Karen H. / SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region. In: Annals of Human Genetics. 2009 ; Vol. 73, No. 3. pp. 274-282.
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