One in four individuals of African-American ancestry harbors a 5.5 kb deletion at chromosome 11q13.1

•Demonstrated heterozygous deletion of 5.5kb sequence on chromosome 11q13.1•This deletion is prevalent in African American (AA) population•The deletion is a founder effect from Yoruban population, ethnic group of Nigeria•Five Single nucleotide polymorphisms are closely linked to the heterozygous deletion•The SNPs are rs11227418, rs495684, rs561948, rs501690 and rs501979•The 5.5kb sequences and SNPs could be used for association studies in AA population

Cloning and sequencing of 5.5 kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines have revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5 kb sequence in 494 normal lymphocyte samples showed heterozygous deletion in 28.3% of African-American ancestry samples but only in 4.8% of Caucasian samples (p < 0.0001). This observation is strengthened by the copy number variation (CNV) data of the HapMap samples which showed that this deletion occurs in 27% of YRI (Yoruba — West African) population but none in non-African populations. The HapMap analysis further identified strong linkage disequilibrium between 5 single nucleotide polymorphisms and the 5.5 kb deletion in people of African ancestry. Computational analysis of 175 kb sequence surrounding the deletion site revealed enhanced flexibility, low thermodynamic stability, high repetitiveness, and stable stem-loop/hairpin secondary structures that are hallmarks of common fragile sites.