Single-nucleotide polymorphisms in the public domain: how useful are they?

Marth, Gábor; Yeh, Raymond T.; Minton, Matthew; Donaldson, Rachel; Qun, LI; Duan, Shenghui; Davenport, R. John; Miller, Raymond D.; Kwok, Pui‐Yan

doi:10.1038/86864

Cited by 149 publications

(93 citation statements)

References 9 publications

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“…3) was done. By March 2001, 2.84 million SNPs had been deposited in a public database, 1.65 million of which were non-redundant [55]. Mapping of the SNPs was performed by sequence comparison with the assembled human genome sequence.…”

Section: The Human Genome Examplementioning

confidence: 99%

A review on SNP and other types of molecular markers and their use in animal genetics

et al. 2002

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-During the last ten years, the use of molecular markers, revealing polymorphism at the DNA level, has been playing an increasing part in animal genetics studies. Amongst others, the microsatellite DNA marker has been the most widely used, due to its easy use by simple PCR, followed by a denaturing gel electrophoresis for allele size determination, and to the high degree of information provided by its large number of alleles per locus. Despite this, a new marker type, named SNP, for Single Nucleotide Polymorphism, is now on the scene and has gained high popularity, even though it is only a bi-allelic type of marker. In this review, we will discuss the reasons for this apparent step backwards, and the pertinence of the use of SNPs in animal genetics, in comparison with other marker types.SNP / microsatellite / molecular marker / genome / polymorphism

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Section: The Human Genome Examplementioning

confidence: 99%

A review on SNP and other types of molecular markers and their use in animal genetics

et al. 2002

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“…This is clearly a situation in which large family-designs are preferable to unrelated samples. Given the current density, marker conversion rate and preponderance of common allele SNPs in the public databases, 30,31 this may be the typical situation for the impending firstgeneration LD maps.…”

Section: Methodsmentioning

confidence: 99%

The impact of genotyping error on haplotype reconstruction and frequency estimation

Kirk

Cardon

2002

Eur J Hum Genet

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The choice of genotyping families vs unrelated individuals is a critical factor in any large-scale linkage disequilibrium (LD) study. The use of unrelated individuals for such studies is promising, but in contrast to family designs, unrelated samples do not facilitate detection of genotyping errors, which have been shown to be of great importance for LD and linkage studies and may be even more important in genotyping collaborations across laboratories. Here we employ some of the most commonly-used analysis methods to examine the relative accuracy of haplotype estimation using families vs unrelateds in the presence of genotyping error. The results suggest that even slight amounts of genotyping error can significantly decrease haplotype frequency and reconstruction accuracy, that the ability to detect such errors in large families is essential when the number/complexity of haplotypes is high (low LD/common alleles). In contrast, in situations of low haplotype complexity (high LD and/or many rare alleles) unrelated individuals offer such a high degree of accuracy that there is little reason for less efficient family designs. Moreover, parent-child trios, which comprise the most popular family design and the most efficient in terms of the number of founder chromosomes per genotype but which contain little information for error detection, offer little or no gain over unrelated samples in nearly all cases, and thus do not seem a useful sampling compromise between unrelated individuals and large families. The implications of these results are discussed in the context of large-scale LD mapping projects such as the proposed genome-wide haplotype map.

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“…Unfortunately, the LD data or allele frequency data necessary to identify a minimal set of dbSNP with reasonable power to detect associations are currently not available for most dbSNPs 14 . As a possible alternative, we examined ascertainment using only dbSNPs reported by multiple groups, as these are much more likely to be common (see Supplementary Table 1 online).…”

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Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans

et al. 2003

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More than 5 million single-nucleotide polymorphisms (SNPs) with minor-allele frequency greater than 10% are expected to exist in the human genome 1 . Some of these SNPs may be associated with risk of developing common diseases 2-4 . To assess the power of currently available SNPs to detect such associations, we resequenced 50 genes in two ethnic samples and measured patterns of linkage disequilibrium between the subset of SNPs reported in dbSNP and the complete set of common SNPs. Our results suggest that using all 2.7 million SNPs currently in the database would detect nearly 80% of all common SNPs in European populations but only 50% of those common in the African American population and that efficient selection of a minimal subset of SNPs for use in association studies requires measurement of allele frequency and linkage disequilibrium relationships for all SNPs in dbSNP.Testing whether common SNPs are associated with modestly higher risk of developing common diseases is an important challenge in human genetics. It has been suggested that a map of over 300,000 SNPs will be required for such genome-wide association studies 5,6 , but it is not yet clear whether the currently available public set of 2.7 million uniquely mapped SNPs is adequate for assembling such a map.We have determined the patterns of common variation in a set of candidate genes related to the inflammatory process by comprehensively resequencing the complete genomic region of each gene in 47 human samples. We selected and sequenced 50 genes distributed across 17 autosomes and spanning 564 kb. We analyzed samples from two ethnic populations, African Americans (24 individuals) and European Americans (23 individuals). Defining a SNP as a biallelic variant, we identified 2,729 SNPs in the 50 genes; defining a common SNP as one with minor-allele frequency greater than 10% in one or both populations, 1,081 of 2,729 SNPs were common (888 in African Americans and 761 in European Americans). The observed frequency of common SNPs (one per 506 bp scanned) suggests that roughly 6 million common SNPs exist in the genome, consistent with previous estimates 1 .We note that only 52% of common SNPs were common in both populations (561 of 1,081; Fig. 1). Defining private polymorphisms as those observed in only one population, 22% of common SNPs in African Americans were private (199 of 888), as were 5% of common SNPs in European Americans (40 of 761). Furthermore, 36% of common SNPs had significantly different frequencies between populations (384 of 1,081 at P < 0.01). Of these, 127 were common in both populations, 185 were common in African Americans but not European Americans and 72 were common in European Americans but not African Americans. Thus, an appreciable fraction of all common variation is either private or common in only a single population, and therefore SNP discovery in a single population is probably inadequate for assembling a catalog of common SNPs that could be used for association studies in all human populations.We used our data set to estim...

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Single-nucleotide polymorphisms in the public domain: how useful are they?

Cited by 149 publications

References 9 publications

A review on SNP and other types of molecular markers and their use in animal genetics

A review on SNP and other types of molecular markers and their use in animal genetics

The impact of genotyping error on haplotype reconstruction and frequency estimation

Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans

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