title: Limitation of number of strains and persistence of false positive loci in QTL mapping using recombinant inbred strains.
abstract: While the identification of causal genes of quantitative trait loci (QTL) remains a difficult problem in the post-genome era, the number of QTL continues to accumulate, mainly identified using the recombinant inbred (RI) strains. Over the last decade, hundreds of publications have reported nearly a thousand QTL identified from RI strains. We hypothesized that the inaccuracy of most of these QTL makes it difficult to identify causal genes. Using data from RI strains derived from C57BL/6J (B6) X DBA/2J (D2), we tested the possibility of detection of reliable QTL with different numbers of strains in the same trait in five different traits. Our results indicated that studies using RI strains of less than 30 in general have a higher probability of failing to detect reliable QTL. Errors in many studies could include false positive loci, switches between QTL with small and major effects, and missing the real major loci. The similar data was obtained from a RI strain population derived from a different pair of parents and a RI strain population of rat. Thus, thousands of reported QTL from studies of RI strains may need to be double-checked for accuracy before proceeding to causal gene identification.
authors.affiliation: Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Department of Basic Medical Research, Inner Mongolia Medical University, Inner Mongolia, China.
authors.forename: Lishi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Mudanjiang Medical College, Mudanjiang, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Institute of Kaschin-Beck Disease, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University; Key Laboratory of Etiologic Epidemiology, Education Bureau of Heilongjiang Province and Ministry of Health (23618104), Harbin, China; Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department. of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Gaifen
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department. of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Weikuan
authors.initials: W
authors.lastname: Gu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D002874:Chromosome Mapping; D003042:Cocaine / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000097:blood* / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000276:immunology; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003900:Desoxycorticosterone; D003042:Cocaine