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The ZBTB7 gene is aberrantly overexpressed in human tumours [1] and is an obvious candidate for a breast cancer low-penetrance gene. Here we aimed to analyze the SNP and haplotypic variability of the ZBTB7 gene in human populations. The information available in SNPs databases is still limited; for example, HapMap contains information of only four ethnic groups, two of them from East Asia [2,3]. The inference of the portability of tagSNPs using this limited amount of information is therefore still under debate. We have thus selected 22 validated polymorphisms covering the ZBTB7 gene and flanking regions using public and private SNP databases. There are more than 1200 worldwide DNA samples (40 human populations), which include those contained in the CEPH Genome Diversity Cell Line Panel. Genotyping was performed using the MassARRAY SNP genotyping system (Sequenom Inc., San Diego, CA, USA). Briefly, it involves multiplex PCR and minisequencing assays, designed with Spectro DESIGNER software (Sequenom Inc.), followed by mass spectrometry analysis with the Bruker Bi-flex MALDI-TOF mass spectrometer (Bruker Daltonics, Billerica, MA, USA). Spectral output was analyzed using SpectroTYPER–RT 3.1 software (Sequenom Inc.) and by manual review.  The present high-density SNP mapping study will facilitate a map of specific population variation and patterns of linkage disequilibrium at the ZBTB7 region in different human populations, and will facilitate the adequate selection of a highly efficient set of tag SNPs that will capture the bulk of the (potentially pathogenic) variation. We have found that patterns of LD and haplotype diversity at the ZBTB7 gene vary considerably among different populations. Thus, sub-Saharan African populations showed higher levels of haplotype diversity and shorter blocks, while non-Africans showed a higher level of LD and lower haplotype diversity, as expected according to population history. According to these patterns, we will discuss the efficiency of these LD patterns and tagSNPs to capture candidate SNPs at the ZBTB7 gene in tumor association studies.

ZBTB7 HapMap in a worldwide population study