Single nucleotide differences (SNDs) in the dbSNP database may lead to errors in genotyping and haplotyping studies
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The creation of single nucleotide polymorphism (SNP) databases (such as NCBI dbSNP) has facilitated scientific research in many fields. SNP discovery and detection has improved to the extent that there are over 17 million human reference (rs) SNPs reported to date (Build 129 of dbSNP). SNP databases are unfortunately not always complete and/or accurate. In fact, half of the reported SNPs are still only candidate SNPs and are not validated in a population. We describe the identification of SNDs (single nucleotide differences) in humans, that may contaminate the dbSNP database. These SNDs, reported as real SNPs in the database, do not exist as such, but are merely artifacts due to the presence of a paralogue (highly similar duplicated) sequence in the genome. Using sequencing we showed how SNDs could originate in two paralogous genes and evaluated samples from a population of 100 individuals for the presence/absence of SNPs. Moreover, using bioinformatics, we predicted as many as 8.32% of the biallelic, coding SNPs in the dbSNP database to be SNDs. Our identification of SNDs in the database will allow researchers to not only select truly informative SNPs for association studies, but also aid in determining accurate SNP genotypes and haplotypes.
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SNPs in AKR1C1, AKR1C2, and AKR1C4 have been studied at the protein level, and Phe46Tyr has been associated with disease.
“So far SNPs in AKR1C1, AKR1C2 and AKR1C4 have been studied at the protein level and Phe46Tyr has been associated with disease [95–97, 99, 103, 104].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [104]
Bioinformatics predicted that 8.3% of biallelic coding SNPs in dbSNP represent single nucleotide differences.
“Based on a bioinformatics approach it has been predicted that 8.3% of biallelic, coding SNPs in the dbSNP database represent single nucleotide differences (SNDs) [104].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [104]
Takahashi et al. functionally characterized 11 nonsynonymous AKR1C2 SNPs known at the time, but later bioinformatics showed only five are real: Phe46Tyr, Val111Ala, Lys179Gln, Lys185Gln, and Arg258Cys.
“In AKR1C2 Takahashi et al. functionally characterized 11 nonsynonymous SNPs known at the time but later bioinformatics studies showed that only 5 of these represent real SNPs: Phe46Tyr, Vall11Ala, Lys179Gln, Lys185Gln and Arg258Cys [104].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [104]
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Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism
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Self-citation
- Authors
- Musumeci, L., Arthur, J. W., Cheung, F. S. G., Hoque, A., Lippman, S., & Reichardt, J. K. V.
- Affiliations
- The University of Sydney (AU)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Reichardt, Juergen K. V.
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2010-01
- Volume
- 31
- Issue
- 1
- Pages
- 67-73
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- PMC
- PMC2797835
- OpenAlex
- W2150709695
- Cited by
- 62
- References
- 18
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 11
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORBi (University of Liège) (submittedVersion, public-domain)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- University of Sydney
- National Cancer Institute (P30CA023100, P01CA108964)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- dbSNP, single nucleotide polymorphisms, paralogs, whole-genome duplication, SNP validation, association studies
- MeSH terms
- Diagnostic Errors, Genotype, Haplotypes, Humans, Genome, Human, Protein Serine-Threonine Kinases, Computational Biology, Internet, Polymorphism, Single Nucleotide, Databases, Genetic, Genetic Association Studies, Aurora Kinases
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