title: Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genetic Causes of Disease Group, Genes and Disease Programme Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain.
authors.forename: Nina
authors.initials: N
authors.lastname: Bosch
authors.forename: Marta
authors.initials: M
authors.lastname: Morell
authors.forename: Immaculada
authors.initials: I
authors.lastname: Ponsa
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Mercader
authors.forename: Lluís
authors.initials: L
authors.lastname: Armengol
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D007446:Chromosome Inversion / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009711:Nucleotides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D013030:Spain
chemical_list: D009711:Nucleotides