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

Abstract

Cloning and sequencing of 5.5kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines has revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5kb 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 5.5kb deletion in the people of African ancestry. Computational analysis of 175kb 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.

Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer

“…We and others have shown that a cervical cancer tumor suppressor gene is localized to chromosome 11q13 and that genomic rearrangements at this site are common in cervical and other human cancers (13,14). We have further shown that homozygous deletion of 5.5kb is seen in HeLa cell derived tumorigenic cell lines and primary tumors indicating the importance of these sequences in tumor development (15)(16)(17). Extensive mapping of the 300kb region localized the 5.5 kb sequence to the 1 st intron of PACS-1, a protein involved in cytoplasmic protein trafficking (15)(16)(17).…”

“…We have further shown that homozygous deletion of 5.5kb is seen in HeLa cell derived tumorigenic cell lines and primary tumors indicating the importance of these sequences in tumor development (15)(16)(17). Extensive mapping of the 300kb region localized the 5.5 kb sequence to the 1 st intron of PACS-1, a protein involved in cytoplasmic protein trafficking (15)(16)(17). The repetitive nature of the 5.5 kb sequence made it extremely difficult to functionally characterize the sequence for its role in tumor development.…”

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

“…The 11q13 locus is well known to contain fragile sites that are prone to breakage. This region has a high frequency of repeats, low GC content, two folate-sensitive fragile sites, potential secondary structures, and a high incidence of cytogenetic and molecular alterations in several cancers [ 55 , [58] , [59] , [60] , [61] ]. Structural variations (SV), which alter chromosomal structure and the DNA copy number, are increasingly recognized as major contributors to genome variability [62] .…”

FADS2 function at the major cancer hotspot 11q13 locus alters fatty acid metabolism in cancer

“…The genetic composition of human chromosome 11q13 is known to contain hotspots for viral integration, harbor fragile sites, copy number variations (CNV) (Figure 2), and various disease phenotypes, including several types of cancers (51)(52)(53)(54). The 11q13 locus is well known to contain fragile sites that are prone to breakage (55). This region has a high frequency of repeats, low GC content, two folate-sensitive fragile sites, potential secondary structures, and a high incidence of cytogenetic and molecular alterations in several cancers (51,(54)(55)(56)(57).…”