Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism

Nina Bosch, Marta Morell, Immaculada Ponsa, Josep Maria Mercader, Lluís Armengol, Xavier P. Estivill

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: The human chromosome 8p23.1 region contains a 3.8-4.5 Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals. Results: We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescent in situ hybridization (FISH). The variability of the 8p23.1 orientation in 150 HapMap samples was predicted using this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentially expressed (p,0.0005) according to the orientation of the 8p23.1 region. Finally, we have found variable levels of mosaicism for the orientation of the 8p23.1 as determined by FISH. Conclusion: By means of dense SNP genotyping of the region, haplotype-based computational analyses and FISH experiments we could infer and verify the orientation status of alleles in the 8p23.1 region by detecting two short haplotype stretches at both ends of the inverted region, which are likely the relic of the chromosome in which the original inversion occurred. Moreover, an impact of 8p23.1 inversion on gene expression levels cannot be ruled out, since four genes from this region have statistically significant different expression levels depending on the inversion status. FISH results in lymphoblastoid cell lines suggest the presence of mosaicism regarding the 8p23.1 inversion.

Original languageEnglish
Article numbere8269
JournalPLoS One
Volume4
Issue number12
DOIs
Publication statusPublished - 2009
Externally publishedYes

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chromosome inversions
inversion polymorphism
Human Chromosomes
Chromosomes
fluorescence in situ hybridization
Polymorphism
Fluorescence In Situ Hybridization
cytogenetics
Cytogenetics
anthropogenic activities
Nucleotides
nucleotides
single nucleotide polymorphism
Single Nucleotide Polymorphism
Mosaicism
genomics
Genes
Haplotypes
haplotypes
HapMap Project

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism. / Bosch, Nina; Morell, Marta; Ponsa, Immaculada; Mercader, Josep Maria; Armengol, Lluís; Estivill, Xavier P.

In: PLoS One, Vol. 4, No. 12, e8269, 2009.

Research output: Contribution to journalArticle

Bosch, Nina ; Morell, Marta ; Ponsa, Immaculada ; Mercader, Josep Maria ; Armengol, Lluís ; Estivill, Xavier P. / Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism. In: PLoS One. 2009 ; Vol. 4, No. 12.
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