Detection of a G>C single nucleotide polymorphism within a repetitive DNA sequence by high-resolution DNA melting

2016 ◽  
Vol 130 (5) ◽  
pp. 1181-1184 ◽  
Author(s):  
Ulrike Schmidt ◽  
Johannes Hulkkonen ◽  
Jana Naue
Blood ◽  
2010 ◽  
Vol 115 (21) ◽  
pp. 4157-4161 ◽  
Author(s):  
Stefan Heinrichs ◽  
Cheng Li ◽  
A. Thomas Look

Comprehensive analysis of the cancer genome has become a standard approach to identifying new disease loci, and ultimately will guide therapeutic decisions. A key technology in this effort, single nucleotide polymorphism arrays, has been applied in hematologic malignancies to detect deletions, amplifications, and loss of heterozygosity (LOH) at high resolution. An inherent challenge of such studies lies in correctly distinguishing somatically acquired, cancer-specific lesions from patient-specific inherited copy number variations or segments of homozygosity. Failure to include appropriate normal DNA reference samples for each patient in retrospective or prospective studies makes it difficult to identify small somatic deletions not evident by standard cytogenetic analysis. In addition, the lack of proper controls can also lead to vastly overestimated frequencies of LOH without accompanying loss of DNA copies, so-called copy-neutral LOH. Here we use examples from patients with myeloid malignancies to demonstrate the superiority of matched tumor and normal DNA samples (paired studies) over multiple unpaired samples with respect to reducing false discovery rates in high-resolution single nucleotide polymorphism array analysis. Comparisons between matched tumor and normal samples will continue to be critical as the field moves from high resolution array analysis to deep sequencing to detect abnormalities in the cancer genome.


2004 ◽  
Vol 44 (7) ◽  
pp. 669 ◽  
Author(s):  
W. Barendse ◽  
R. Bunch ◽  
M. Thomas ◽  
S. Armitage ◽  
S. Baud ◽  
...  

The TG5 (thyroglobulin 5′ leader sequence) single nucleotide polymorphism has been associated with marbling in cattle fed for periods longer than 250 days. To test whether the association could be detected in diverse cattle, fed for less than 250 days, and to measure the size of the effect, we sampled 1750 cattle from the AMH Toowoomba feedlot. These cattle were sampled on 28 separate days, over 9 months. Their marbling scores covered the complete range. We found that the TG5 single nucleotide polymorphism was associated with marbling scores (P<0.05) and estimated that TG5 genotypes explained 6.5% of the residual deviance for the marbling phenotype. We also found that the '3' allele was more frequent in animals with higher marbling scores. The consistency of the allelic association between studies and, in particular, the association found in diverse cattle, indicate that the TG5 polymorphism can be used as a breeding tool and possibly a feedlot entry tool. To estimate the size of the genetic region in which the marbling quantitative trait loci are located, we tested the nearby DNA markers CSSM66 and BMS1747. These do not show allelic associations to marbling. The consistency of the allelic association between studies, the lack of association to nearby DNA markers and the complementary information on gene action of genes near Thyroglobulin suggest that DNA sequence variations, in or near the Thyroglobulin gene sequence, are the likely causes for the marbling quantitative trait loci. Further studies of single nucleotide polymorphism in and near the Thyroglobulin DNA sequence should allow causal mutations for the effect to be identified.


Sign in / Sign up

Export Citation Format

Share Document