title: One in four individuals of African-American ancestry harbors a 5.5kb deletion at chromosome 11q13.1.
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.
authors.affiliation: Division of General Surgery, Department of Surgery, VAGLAHS West Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.
authors.forename: Kayvan
authors.initials: K
authors.lastname: Zainabadi
authors.affiliation: Division of General Surgery, Department of Surgery, VAGLAHS West Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.
authors.forename: Anuja V
authors.initials: AV
authors.lastname: Jain
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Frank X
authors.initials: FX
authors.lastname: Donovan
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA.
authors.forename: Nagesh P
authors.initials: NP
authors.lastname: Rao
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.affiliation: Division of General Surgery, Department of Surgery, VAGLAHS West Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. Electronic address: esrivats@ucla.edu.
authors.forename: Eri S
authors.initials: ES
authors.lastname: Srivatsan
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D043283:Chromosome Fragile Sites; D002880:Chromosomes, Human, Pair 11; D056915:DNA Copy Number Variations; D005260:Female; D018703:Founder Effect; D060148:HapMap Project; D006367:HeLa Cells; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
keywords: 5.5kb deletion; African American ancestry; Cervical cancer; Chromosome 11q13.1; Common fragile site; Linkage disequilibrium; Single nucleotide polymorphisms