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Genotyping Technologies (genotyping + technology)

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Life Sciences	100%

Selected Abstracts

Restricted parameter space models for testing gene-gene interaction

GENETIC EPIDEMIOLOGY, Issue 5 2009
Minsun Song
Abstract There is a growing recognition that interactions (gene-gene and gene-environment) can play an important role in common disease etiology. The development of cost-effective genotyping technologies has made genome-wide association studies the preferred tool for searching for loci affecting disease risk. These studies are characterized by a large number of investigated SNPs, and efficient statistical methods are even more important than in classical association studies that are done with a small number of markers. In this article we propose a novel gene-gene interaction test that is more powerful than classical methods. The increase in power is due to the fact that the proposed method incorporates reasonable constraints in the parameter space. The test for both association and interaction is based on a likelihood ratio statistic that has a x,2 distribution asymptotically. We also discuss the definitions used for "no interaction" and argue that tests for pure interaction are useful in genome-wide studies, especially when using two-stage strategies where the analyses in the second stage are done on pairs of loci for which at least one is associated with the trait. Genet. Epidemiol. 33:386,393, 2009. © 2008 Wiley-Liss, Inc. [source]

Novel PlexorÔ SNP genotyping technology: comparisons with TaqMan® and homogenous MassEXTENDÔ MALDI-TOF mass spectrometry,

HUMAN MUTATION, Issue 9 2007
E.A. Tindall
Abstract Analysis of SNPs for association, linkage, haplotype, and pharmacogenetic studies has led to a dramatic increase in the number and evolution of medium- to high-throughput genotyping technologies. This study introduces PlexorÔ as a new method for medium-throughput (single SNP) genotyping. We compare this fluorescent-based chemistry for call rate, accuracy, affordability, throughput, and overall efficiency against two commonly used technologies. These include fluorescent-based TaqMan® allelic discrimination for single SNP analysis (medium-throughput) and the homogenous MassEXTENDÔ (hMEÔ) chemistry using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for multiple SNP analysis (high-throughput). Analysis of 11 SNPs, including all six possible nucleotide substitutions, showed PlexorÔ to be highly comparable for both call rate (94.7%) and accuracy (99.2%) to the TaqMan® (94.6% and 99.8%, respectively) and hMEÔ (91.9% and 98.1%, respectively) chemistries. We demonstrate that this novel method is an efficient, cost-effective alternative to TaqMan® genotyping commonly used in diagnostic settings. Hum Mutat 28(9), 922,927, 2007. © 2007 Wiley-Liss, Inc. [source]

Using linked markers to infer the age of a mutation

HUMAN MUTATION, Issue 2 2001
Bruce Rannala
Abstract Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a "direct" estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine-tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine-scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as "composite" likelihood and moment-based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87,100, 2001. © 2001 Wiley-Liss, Inc. [source]

Noninvasive prenatal diagnosis of fetal blood group phenotypes: current practice and future prospects

PRENATAL DIAGNOSIS, Issue 2 2009
Geoff Daniels
Abstract Fetuses of women with alloantibodies to RhD (D) are at risk from hemolytic disease of the fetus and newborn, but only if the fetal red cells are D-positive. In such pregnancies, it is beneficial to determine fetal D type, as this will affect the management of the pregnancy. It is possible to predict, with a high level of accuracy, fetal blood group phenotypes from genotyping tests on fetal DNA. The best source is the small quantity of fetal DNA in the blood of pregnant women, as this avoids the requirement for invasive procedures of amniocentesis or chorionic villus sampling (CVS). Many laboratories worldwide now provide noninvasive fetal D genotyping as a routine service for alloimmunized women, and some also test for c, E, C and K. In many countries, anti-D immunoglobulin injections are offered to D-negative pregnant women, to reduce the chances of prenatal immunization, even though up to 40% of these women will have a D-negative fetus. High-throughput, noninvasive fetal D genotyping technologies are being developed so that unnecessary treatment of pregnant women can be avoided. Trials suggest that fetal D typing of all D-negative pregnant women is feasible and should become common practice in the near future. Copyright © 2008 John Wiley & Sons, Ltd. [source]

The combined effect of SNP-marker and phenotype attributes in genome-wide association studies

ANIMAL GENETICS, Issue 2 2009
E. K. F. Chan
Summary The last decade has seen rapid improvements in high-throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome-wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is imperative to appropriately pre-process, or filter out, those SNPs that may lead to false associations. This paper explores the relationships between various SNP genotype and phenotype attributes and their effects on false associations. We show that (i) uniformly distributed ordinal data as well as binary data are more easily influenced, though not necessarily negatively, by differences in various SNP attributes compared with normally distributed data; (ii) filtering SNPs on minor allele frequency (MAF) and extent of Hardy,Weinberg equilibrium (HWE) deviation has little effect on the overall false positive rate; (iii) in some cases, filtering on MAF only serves to exclude SNPs from the analysis without reduction of the overall proportion of false associations; and (iv) HWE, MAF and heterozygosity are all dependent on minor genotype frequency, a newly proposed measure for genotype integrity. [source]

Biotec Visions 2009, November,December

BIOTECHNOLOGY JOURNAL, Issue 11 2009
Article first published online: 13 NOV 200
Nobel Prizes 2009: Ribosomes , Telomeres and telomerases Encyclopaedia of Life Sciences: SNP genotyping technologies , Molecular mimicry Special issues: Chinese microbial ecology , Advances in yeast proteomics , MALDI-TOF "Flip-flop" drug susceptibility test News: Phytophthora infestans genome , Sequencing bacterial transcriptomes , Stem cells from fat , Selecting green clones , Endogenous mutagenic force , Green batteries , Tobacco-produced vaccine , O2 transport in artificial liver , Endolysins instead of antibiotics , Quick switch key for mitochondria , Climate change shrinks algae , Bacteria degrade microcystins Opinion: Will biotech banish wrinkles forever? Most Read Synthetic biology Tips and tricks: Trypsinizing cells Biotech round the world: Kenya Writing Tips: IMRAD or RAMID? Briefs: Metabolic Engineering award , Mosquitoes , from foe to friend , Mobile phone microscope Test your Knowledge: Do you recognize this? In Brief: The horse pathogen Rhodococcus equi [source]

A principal components regression approach to multilocus genetic association studies

GENETIC EPIDEMIOLOGY, Issue 2 2008
Kai Wang
Abstract With the rapid development of modern genotyping technology, it is becoming commonplace to genotype densely spaced genetic markers such as single nucleotide polymorphisms (SNPs) along the genome. This development has inspired a strong interest in using multiple markers located in the target region for the detection of association. We introduce a principal components (PCs) regression method for candidate gene association studies where multiple SNPs from the candidate region tend to be correlated. In this approach, the total variance in the original genotype scores is decomposed into parts that correspond to uncorrelated PCs. The PCs with the largest variances are then used as regressors in a multiple regression. Simulation studies suggest that this approach can have higher power than some popular methods. An application to CHI3L2 gene expression data confirms a significant association between CHI3L2 gene expression level and SNPs from this gene that has been previously reported by others. Genet. Epidemiol. 2008. © 2007 Wiley-Liss, Inc. [source]