Loss of information due to ambiguous haplotyping of SNPs

Se, Hodge; Boehnke, Michael; Ma, Spence

doi:10.1038/7687

Cited by 83 publications

(42 citation statements)

References 6 publications

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“…This is consistent with the strong negative correlation between the mean pair-wise LD and haplotype heterozygosity, supporting the concept that the stronger the non-random association between SNPs, the lower the information added by each SNP to a set of other SNPs (Cambien et al 1999). On the other hand, some information will be lost because of the ambiguous haplotyping of multiple SNPs, if linkage equilibrium is reached between SNP sites (Hodge et al 1999;Hoh and Hodge 2000). A fine balance of LD between multiple SNP sites is therefore required to obtain the maximum information within a genomic region and the knowledge of the extent and magnitude of LD between SNPs should be invaluable in the selection of the SNP set for linkage analysis.…”

Section: Discussionmentioning

confidence: 98%

Effectiveness of computational methods in haplotype prediction

Lewis

Cantone

et al. 2001

Hum Genet

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Haplotype analysis has been used for narrowing down the location of disease-susceptibility genes and for investigating many population processes. Computational algorithms have been developed to estimate haplotype frequencies and to predict haplotype phases from genotype data for unrelated individuals. However, the accuracy of such computational methods needs to be evaluated before their applications can be advocated. We have experimentally determined the haplotypes at two loci, the N-acetyltransferase 2 gene ( NAT2, 850 bp, n=81) and a 140-kb region on chromosome X ( n=77), each consisting of five single nucleotide polymorphisms (SNPs). We empirically evaluated and compared the accuracy of the subtraction method, the expectation-maximization (EM) method, and the PHASE method in haplotype frequency estimation and in haplotype phase prediction. Where there was near complete linkage disequilibrium (LD) between SNPs (the NAT2 gene), all three methods provided effective and accurate estimates for haplotype frequencies and individual haplotype phases. For a genomic region in which marked LD was not maintained (the chromosome X locus), the computational methods were adequate in estimating overall haplotype frequencies. However, none of the methods was accurate in predicting individual haplotype phases. The EM and the PHASE methods provided better estimates for overall haplotype frequencies than the subtraction method for both genomic regions.

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Section: Discussionmentioning

confidence: 98%

Effectiveness of computational methods in haplotype prediction

Lewis

Cantone

et al. 2001

Hum Genet

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“…Most studies to date have relied on single polymorphisms instead of haplotype-based analyses, even if the latter approach has been shown to be more informative than genotype analysis of single variants [11]. In our recent study [12], maximum likelihood estimates of haplotype frequencies and tests of linkage disequilibrium between investigated AGT polymorphisms and a putative quantitative trait locus (QTL) were in agreement with a complete confounding of AGT C-532T with the QTL.…”

Section: Introductionmentioning

confidence: 88%

Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives

Brand-Herrmann¹,

Köpke

Reichenberger

et al. 2004

Journal of Hypertension

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“…However, the current methods for determining haplotypes have significant limitations that have prevented their use in large-scale genetic screening. For example, parental genotyping can be used to infer haplotypes in a family study (Hodge et al, 1999;Sobel and Lange, 1996), although in many cases it is impractical or impossible to obtain parental DNA.…”

Section: Dna Sequence Analysis and Haplotypingmentioning

confidence: 99%

Structural and functional imaging with carbon nanotube AFM probes

Hafner

Cheung

Woolley

et al. 2001

Progress in Biophysics and Molecular Biology

317

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Atomic force microscopy (AFM) has great potential as a tool for structural biology, a field in which there is increasing demand to characterize larger and more complex biomolecular systems. However, the poorly characterized silicon and silicon nitride probe tips currently employed in AFM limit its biological applications. Carbon nanotubes represent ideal AFM tip materials due to their small diameter, high aspect ratio, large Young's modulus, mechanical robustness, well-defined structure, and unique chemical properties. Nanotube probes were first fabricated by manual assembly, but more recent methods based on chemical vapor deposition provide higher resolution probes and are geared towards mass production, including recent developments that enable quantitative preparation of individual single-walled carbon nanotube tips [J. Phys. Chem. B 105 (2001) 743]. The high-resolution imaging capabilities of these nanotube AFM probes have been demonstrated on gold nanoparticles and well-characterized biomolecules such as IgG and GroES. Using the nanotube probes, new biological structures have been investigated in the areas of amyloid-beta protein aggregation and chromatin remodeling, and new biotechnologies have been developed such as AFM-based haplotyping. In addition to measuring topography, chemically functionalized AFM probes can measure the spatial arrangement of chemical functional groups in a sample. However, standard silicon and silicon nitride tips, once functionalized, do not yield sufficient resolution to allow combined structural and functional imaging of biomolecules. The unique end-group chemistry of carbon nanotubes, which can be arbitrarily modified by established chemical methods, has been exploited for chemical force microscopy, allowing single-molecule measurements with well-defined functionalized tips.

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Loss of information due to ambiguous haplotyping of SNPs

Cited by 83 publications

References 6 publications

Effectiveness of computational methods in haplotype prediction

Effectiveness of computational methods in haplotype prediction

Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives

Structural and functional imaging with carbon nanotube AFM probes

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