SNPs/pools: a methodology for the identification of relevant SNPs in breast cancer epidemiology.
The identification of allelic variants of human genes is of great importance             when assessing genetic susceptibility. The emerging role of genetic polymorphisms             in association studies has created the need for high throughput genotyping methodologies             that allow a more rapid identification of relevant polymorphisms related to individual             cancer risk enabling the extension to large-scale association studies. DNA pooling             methodology may be of great importance considering the cost, time and labor that             are involved in large-scale genotyping analysis carried out on individual samples.             Alternatively, when using pooled samples which are made up of DNA from many individuals             treated as a single sample, these factors are decrease drastically. In this way,             the use of DNA pooling methodology, as a pre-selection tool, allows the identification             of the most relevant polymorphisms to be studied, facilitating the estimation             of the allelic frequency of each SNP in different populations. The present study             initially aimed to validate the DNA pooling approach for the identification of             genetic polymorphisms potentially associated with individual cancer risk generating             pools with known allelic frequencies and using studies ongoing in the laboratory.             Finally, our main aim was to test the accuracy of the pooled DNA analysis comparing             the results of the allelic frequencies determined using pooled samples with the             allelic frequency previously estimated by individual genotyping and previously             published. In order to analyze the possibility of establishing differences between             populations, we created DNA pools using a Portuguese control population, a breast             cancer population and a Xavante Indian population characterized by a total absence             of breast cancer cases. The pools were firstly created with known allelic frequencies,             previously determined by individual genotyping, and, latter, randomly incremented             in sample size to 200 patients and controls. Our results showed that the DNA pooling             approach was a useful tool for the analysis of allelic distribution in the different             populations studied. Ιn conclusion, our results showed that this methodology can             be applied as an effective approach to identify SNPs of importance in genetic             susceptibility to disease which may be used in association studies conducted subsequently             by individual genotyping.
Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, and Department of Clinical Pathology, Hospital Sãko Francisco Xavier, Rua da Junqueira 100, P-1349-008 Lisbon, Portugal. snsilva.gene@fcm.unl.pt
Susana N
SN
Silva
Daniela
D
Guerreiro
Mafalda
M
Gomes
Ana Paula
AP
Azevedo
Guilherme
G
Bezerra De Castro
José
J
Rueff
Jorge F
JF
Gaspar
D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D060005:Genotyping Techniques; D006801:Humans; D020641:Polymorphism, Single Nucleotide