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High-throughput Single Nucleotide Polymorphism (high-throughput + single_nucleotide_polymorphism)
Selected AbstractsMicrosatellites versus single-nucleotide polymorphisms in confidence interval estimation of disease lociGENETIC EPIDEMIOLOGY, Issue 1 2006Charalampos Papachristou Abstract With cost-effective high-throughput Single Nucleotide Polymorphism (SNP) arrays now becoming widely available, it is highly anticipated that SNPs will soon become the choice of markers in whole genome screens. This optimism raises a great deal of interest in assessing whether dense SNP maps offer at least as much information as their microsatellite (MS) counterparts. Factors considered to date include information content, strength of linkage signals, and effect of linkage disequilibrium. In the current report, we focus on investigating the relative merits of SNPs vs. MS markers for disease gene localization. For our comparisons, we consider three novel confidence interval estimation procedures based on confidence set inference (CSI) using affected sib-pair data. Two of these procedures are multipoint in nature, enabling them to capitalize on dense SNPs with limited heterozygosity. The other procedure makes use of markers one at a time (two-point), but is much more computationally efficient. In addition to marker type, we also assess the effects of a number of other factors, including map density and marker heterozygosity, on disease gene localization through an extensive simulation study. Our results clearly show that confidence intervals derived based on the CSI multipoint procedures can place the trait locus in much shorter chromosomal segments using densely saturated SNP maps as opposed to using sparse MS maps. Finally, it is interesting (although not surprising) to note that, should one wish to perform a quick preliminary genome screening, then the two-point CSI procedure would be a preferred, computationally cost-effective choice. Genet. Epidemiol. 30:3,17, 2006. © 2005 Wiley-Liss, Inc. [source] Single nucleotide polymorphism genotyping of the barley waxy gene by polymerase chain reaction with confronting two-pair primersPLANT BREEDING, Issue 3 2004E. Domon Abstract A high-throughput single nucleotide polymorphism (SNP) genotyping procedure was developed to select amylose-free barley mutants whose waxy genes had a C- to T-base substitution in exon 5, which converted Gln-89 of the wild-type gene into a termination codon. An F2 population carrying an amylose-free waxy gene was checked for segregation. Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) produced allele-specific PCR products that have different sizes and are inherited in a co-dominant manner. Two alleles of the barley waxy gene with SNP were correctly identified in parental strains using the PCR-CTPP procedure. Segregation of the SNP as detected by PCR-CTPP in an F2 population fitted the expected 1:2:1 ratio. The PCR-CTPP procedure can provide a time saving and cost-effective alternative to derived cleaved amplified polymorphic sequence in marker-assisted selection. [source] Genome-wide scan for bovine twinning rate QTL using linkage disequilibriumANIMAL GENETICS, Issue 3 2009E.-S. Kim Summary Twinning is a complex trait with negative impacts on health and reproduction, which cause economic loss in dairy production. Several twinning rate quantitative trait loci (QTL) have been detected in previous studies, but confidence intervals for QTL location are broad and many QTL are unreplicated. To identify genomic regions or genes associated with twinning rate, QTL analysis based on linkage combined with linkage disequilibrium (LLD) and individual marker associations was conducted across the genome using high-throughput single nucleotide polymorphism (SNP) genotypes. A total of 9919 SNP markers were genotyped with 200 sires and sons in 19 half-sib North American Holstein dairy cattle families. After SNPs were genotyped, informative markers were selected for genome-wide association tests and QTL searches. Evidence for twinning rate QTL was found throughout the genome. Thirteen markers significantly associated with twinning rate were detected on chromosomes 2, 5 and 14 (P < 2.3 × 10,5). Twenty-six regions on fourteen chromosomes were identified by LLD analysis at P < 0.0007. Seven previously reported ovulation or twinning rate QTL were supported by results of single marker association or LLD analyses. Single marker association analysis and LLD mapping were complementary tools for the identification of putative QTL in this genome scan. [source] The combined effect of SNP-marker and phenotype attributes in genome-wide association studiesANIMAL GENETICS, Issue 2 2009E. 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] | ||||||||||