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

Genomics. 2014 Apr;103(4):276-87. doi: 10.1016/j.ygeno.2014.01.001. Epub 2014 Jan 10.

Abstract

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.

Keywords: 5.5kb deletion; African American ancestry; Cervical cancer; Chromosome 11q13.1; Common fragile site; Linkage disequilibrium; Single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Black or African American / genetics*
  • Chromosome Deletion*
  • Chromosome Fragile Sites
  • Chromosomes, Human, Pair 11*
  • DNA Copy Number Variations
  • Female
  • Founder Effect
  • HapMap Project
  • HeLa Cells
  • Heterozygote
  • Humans
  • Linkage Disequilibrium
  • Male
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide*