Nucleotide, Cytogenetic and Expression Impact of the Human Chromosome 8p23.1 Inversion Polymorphism 英文参考文献.docVIP

Nucleotide,CytogeneticandExpressionImpactofthe HumanChromosome8p23.1InversionPolymorphism NinaBosch1,2,MartaMorell1,2,ImmaculadaPonsa1,3,4,JosepMariaMercader1,2,Llu?′sArmengol1,2,5 , XavierEstivill1,2,6 * 1GeneticCausesofDiseaseGroup,GenesandDiseaseProgrammeCenterforGenomicRegulation(CRG-UPF),Barcelona,Catalonia,Spain,2CIBERenEpidemiolog?′ay Salud Pu′blica (CIBERESP), Barcelona, Catalonia, Spain, 3Departament de Biologia Cel?lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Auto`noma de Barcelona,Catalonia,Spain,4InstitutdeBiotecnologiaiBiomedicina,UniversitatAuto`nomadeBarcelona,Barcelona,Catalonia,Spain,5QuantitativeGenomicMedicine Laboratories(qGenomics),Barcelona,Catalonia,Spain,6DepartmentofHealthandExperimentalLifeSciences,PompeuFabraUniversity(UPF),Barcelona,Catalonia,Spain Abstract Background: The human chromosome 8p23.1 region contains a 3.8–4.5Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs)tightlylinkedtothegenomicorientationofagivenregionshouldbeusefultoindirectlyevaluatethegenotypesof largegenomicorientationsintheindividuals. Results: We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescentinsituhybridization(FISH).Thevariabilityofthe8p23.1orientationin150HapMapsampleswaspredictedusing this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentiallyexpressed(p,0.0005)accordingtotheorientationofthe8p23.1region.Finally,wehavefoundvariablelevels ofmosaicismfortheorientationofthe8p23.1asdeterminedbyFISH. Conclusion: By means of dense SNP genotyping of the region, haplotype-based computational analyses and FISH experimentswecouldinferandverifytheorientationstatusofallelesinthe8p23.1regionbydetectingtwoshorthaplotype stretchesatbothendsoftheinvertedregion,whicharelikelytherelicofthechromosomeinwh