An integrated system for high throughput

  TaqMan™ based SNP genotyping

The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.aging ͉ forkhead box O3A ͉ genetic association study ͉ long-lived individuals

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“…Genotyping of the German and French samples was performed with Taqman SNP Genotyping Assays (Applied Biosystems) on an automated platform (23).…”

Section: Methodsmentioning

confidence: 99%

Association of FOXO3A variation with human longevity confirmed in German centenarians

Flachsbart¹,

Caliebe

Kleindorp³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

549

391

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“…34 Statistical analyses Each marker was tested for Hardy -Weinberg equilibrium in the control populations using a w 2 test. Genetic analyses were then performed at several levels.…”

Section: Methodsmentioning

confidence: 99%

Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations

et al. 2003

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Current debate focuses on the relevance of linkage disequilibrium (LD), ethnicity and underlying haplotype structure to the search for genes involved in complex disorders. The recently described association between single nucleotide polymorphisms (SNPs) of the CARD15 (NOD2) gene and Crohn's disease (CD) in populations of north-European descent provides a test case that we have subjected to detailed SNP haplotype based analyses. We examined 23 SNPs spanning 290 kb, including CARD15, in large North-European and Korean samples of patients with Crohn's disease and normal controls. In Europeans we confirmed that the three disease-associated SNPs occur independently but share a common background haplotype. This suggests a common origin and the possibility of an undiscovered more strongly predisposing mutation. Korean CD patients present a phenotype identical to the European patients and have not previously been screened for CARD15. The three disease-associated SNPs were absent and there was no evidence of association between CARD15 and CD. Consequently, the diseaseassociated mutations in the Europeans, which are rare, have arisen recently (after the Asian -European split). Our results highlight important issues relevant to mapping the genes that predispose to complex disorders. First, although ethnically divergent populations may present identical phenotypes they do not necessarily share the same set of predisposing genes. Second, although single-locus tests of association showed consistent association with markers throughout the gene, pair-wise LD between markers (r 2 and D') yielded very little information about actual disease-association. Third, a population comparative approach allowed refining of the marker set through the examination of shared polymorphisms and common LD-groups. This approach, in conjunction with the examination of the mutational steps in a haplotype network, allows unambiguous identification of the potentially causative mutations.

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“…The four functionally relevant SNPs (the exonic SNP rs1061622 and the three neighboring 39UTR markers rs1061624, rs5030792, and rs3397) in the TNFRSF1B gene were typed using TaqMan SNP Assays (see Table E1, in the online supplement) or the SNPlex Genotyping System (Applied Biosystems, Foster City, CA) as previously described (22,23). Samples from positive and negative control subjects were included on each genotyping plate and checked for consistency.…”

Section: Genotyping and Statistical Analysismentioning

confidence: 99%

A Functional Haplotype in the 3′Untranslated Region ofTNFRSF1BIs Associated with Tuberculosis in Two African Populations

Möller¹,

Flachsbart²,

Till³

et al. 2010

Am J Respir Crit Care Med

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An integrated system for high throughput TaqMan™ based SNP genotyping

Abstract: The SQL source code, sources and binaries of the client applications (NT and Windows95/98 platforms) and additional documentation are available at http://www.mucosa.de/.

Cited by 95 publications

References 7 publications

Association of FOXO3A variation with human longevity confirmed in German centenarians

Association of FOXO3A variation with human longevity confirmed in German centenarians

Haplotype structure and association to Crohn's disease of CARD15 mutations in two ethnically divergent populations

A Functional Haplotype in the 3′Untranslated Region ofTNFRSF1BIs Associated with Tuberculosis in Two African Populations

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