Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests Susceptibility Loci on Chromosomes 3q25-26 and 21q22 英文参考文献.docVIP

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Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests Susceptibility Loci on Chromosomes 3q25-26 and 21q22 英文参考文献.doc

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Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests Susceptibility Loci on Chromosomes 3q25-26 and 21q22 英文参考文献

Genome-WideLinkageScanofaPedigreewithFamilial HypercholesterolemiaSuggestsSusceptibilityLocion Chromosomes3q25-26and21q22 XuWang1.,XinLi2.,Yong-BiaoZhang2,FengZhang2,LiyuanSun1,JieLin1,Duen-MeiWang2 ,Lu-Ya Wang1* 1The Key Laboratory of Remodeling-related Cardiovascular Diseases, Capital Medical University, Ministry of Education, and Beijing Institute of Heart Lung and Blood VesselDiseases,BeijingAnzhenHospitaloftheCapitalUniversityofMedicalSciences,Beijing,People’sRepublicofChina,2CASKeyLaboratoryofGenomeSciencesand Information,BeijingInstituteofGenomics,ChineseAcademyofSciences,Beijing,People’sRepublicofChina Abstract Background: Familial hypercholesterolemia (FH) is a heritable disorder that can increase the risk of premature coronary heart disease. Studies suggest there are substantial genetic heterogeneities for different populations. Here we tried to identifynovelsusceptibilitylociforFHinaChinesepedigree. Methodology/Principal Findings: Weperformed aSNP-based genome-widelinkage scanwiththeChineseFHpedigree. Two suggestive linkage loci not previously reported were identified on chromosomes 3q25.1-26.1 (NPL=9.01, nominal P,0.00001,andsimulatedoccurrencepergenomescan=1.08)and21q22.3(NPL=8.95,nominalP,0.00001,andsimulated occurrence per genome scan=1.26). In the interaction analysis with a trimmed version of the pedigree, we obtained a significantly increased joint LOD score (2.70) compared with that obtained when assuming the two loci uncorrelated, suggestingthatmorethanonelocuswasinvolvedinthispedigree.ExonscreeningoftwocandidategenesABCG1andLSS fromoneofthesuggestiveregion21q22didn’treportanycausativemutations. Conclusions/Significances: These results confirm complex etiologies and suggest new genetic casual factors for the FH disorder.Furtherstudyofthetwocandidateregionsisadvocated. Citation: Wang X, Li X, Zhang Y-B, Zhang F, Sun L, et al. (2011) Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests SusceptibilityLocionChromosomes