Showing papers by "David Altshuler published in 2000"
TL;DR: The nucleic acids, primers and probes are used in applications such as phenotype correlations, forensics, paternity testing, medicine and genetic analysis as mentioned in this paper, where the nucleic acid segments from the coding region of a gene, including polymorphic sites are provided.
Abstract: The invention provides nucleic acid segments of the human genome, particularly nucleic acid segments from the coding region of a gene, including polymorphic sites. Allele-specific primers and probes hybridizing to regions flanking or containing these sites are also provided. The nucleic acids, primers and probes are used in applications such as phenotype correlations, forensics, paternity testing, medicine and genetic analysis.
1,742 citations
TL;DR: By analysing over 3,000 individuals, this work found a modest but significant increase in diabetes risk associated with the more common proline allele, which translates into a large population attributable risk—influencing as much as 25% of type 2 diabetes in the general population.
Abstract: Genetic association studies are viewed as problematic and plagued by irreproducibility. Many associations have been reported for type 2 diabetes, but none have been confirmed in multiple samples and with comprehensive controls. We evaluated 16 published genetic associations to type 2 diabetes and related sub-phenotypes using a family-based design to control for population stratification, and replication samples to increase power. We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(PPARgamma) with type 2 diabetes. By analysing over 3,000 individuals, we found a modest (1.25-fold) but significant (P=0.002) increase in diabetes risk associated with the more common proline allele (85% frequency). Moreover, our results resolve a controversy about common variation in PPARgamma. An initial study found a threefold effect, but four of five subsequent publications failed to confirm the association. All six studies are consistent with the odds ratio we describe. The data implicate inherited variation in PPARgamma in the pathogenesis of type 2 diabetes. Because the risk allele occurs at such high frequency, its modest effect translates into a large population attributable risk-influencing as much as 25% of type 2 diabetes in the general population.
1,698 citations
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TL;DR: Progress is reported by Bell and colleagues in their study of NIDDM1, a locus implicated in type 2 diabetes, a complex nature of the reported association illustrates the challenge of implicating a specific gene and mutation in the causation of polygenic disease.
Abstract: Positional cloning of common disease genes is a central but elusive goal of human geneticists. Progress is now reported by Bell and colleagues in their study of NIDDM1, a locus implicated in type 2 diabetes. The complex nature of the reported association illustrates the challenge of implicating a specific gene and mutation in the causation of polygenic disease.
826 citations
TL;DR: A simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps, which facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species.
Abstract: Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history. It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases. Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping.
749 citations