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 T Nigg; Karen H Friderici

doi:10.1111/j.1469-1809.2009.00513.x

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

Journal article

Peer reviewed

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 T Nigg and Karen H Friderici

Annals of human genetics, Vol.73(Pt 3), pp.274-282

05/2009

DOI: 10.1111/j.1469-1809.2009.00513.x

PMCID: PMC2749463

PMID: 19397556

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https://www.ncbi.nlm.nih.gov/pmc/articles/2749463View

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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.

Base Sequence

Chromosome Mapping

Gene Duplication

Genetic Techniques

Haplotypes

Humans

Molecular Sequence Data

Open Reading Frames

Polymorphism, Single Nucleotide

Pseudogenes

Receptors, Dopamine D5 - genetics

Triplets - genetics

Details

Title: Subtitle: SNP discovery and haplotype analysis in the segmentally duplicated DRD5 coding region
Creators: Donna J E Housley - Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, USA
Molly Nikolas
Patrick J Venta
Kathrine A Jernigan
Irwin D Waldman
Joel T Nigg
Karen H Friderici
Resource Type: Journal article
Publication Details: Annals of human genetics, Vol.73(Pt 3), pp.274-282
DOI: 10.1111/j.1469-1809.2009.00513.x
PMID: 19397556
PMCID: PMC2749463
NLM abbreviation: Ann Hum Genet
ISSN: 0003-4800
eISSN: 1469-1809
Grant note: R01MH070004 / NIMH NIH HHS R01 MH070004 / NIMH NIH HHS R01 MH070004-04 / NIMH NIH HHS
Language: English
Date published: 05/2009
Academic Unit: Psychological and Brain Sciences; Injury Prevention Research Center
Record Identifier: 9984214750002771

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