Box–Cox transformation for QTL mapping

Yang, Runqing; Yi, Nengjun; Xu, Shizhong

doi:10.1007/s10709-005-5577-z

Cited by 19 publications

(11 citation statements)

References 21 publications

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“…2). The Box-Cox transformation [48] was used to determine the optimal transformation for trait 1 that deviated from the normal distribution, resulting in approximately normally distributed data. Total DNA was extracted from the fin clips according to LAIRD et al .…”

Section: Methodsmentioning

confidence: 99%

Discovery and application of insertion-deletion (INDEL) polymorphisms for QTL mapping of early life-history traits in Atlantic salmon

et al. 2010

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BackgroundFor decades, linkage mapping has been one of the most powerful and widely used approaches for elucidating the genetic architecture of phenotypic traits of medical, agricultural and evolutionary importance. However, successful mapping of Mendelian and quantitative phenotypic traits depends critically on the availability of fast and preferably high-throughput genotyping platforms. Several array-based single nucleotide polymorphism (SNP) genotyping platforms have been developed for genetic model organisms during recent years but most of these methods become prohibitively expensive for screening large numbers of individuals. Therefore, inexpensive, simple and flexible genotyping solutions that enable rapid screening of intermediate numbers of loci (~75-300) in hundreds to thousands of individuals are still needed for QTL mapping applications in a broad range of organisms.ResultsHere we describe the discovery of and application of insertion-deletion (INDEL) polymorphisms for cost-efficient medium throughput genotyping that enables analysis of >75 loci in a single automated sequencer electrophoresis column with standard laboratory equipment. Genotyping of INDELs requires low start-up costs, includes few standard sample handling steps and is applicable to a broad range of species for which expressed sequence tag (EST) collections are available. As a proof of principle, we generated a partial INDEL linkage map in Atlantic salmon (Salmo salar) and rapidly identified a number of quantitative trait loci (QTLs) affecting early life-history traits that are expected to have important fitness consequences in the natural environment.ConclusionsThe INDEL genotyping enabled fast coarse-mapping of chromosomal regions containing QTL, thus providing an efficient means for characterization of genetic architecture in multiple crosses and large pedigrees. This enables not only the discovery of larger number of QTLs with relatively smaller phenotypic effect but also provides a cost-effective means for evaluation of the frequency of segregating QTLs in outbred populations which is important for further understanding how genetic variation underlying phenotypic traits is maintained in the wild.

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Section: Methodsmentioning

confidence: 99%

Discovery and application of insertion-deletion (INDEL) polymorphisms for QTL mapping of early life-history traits in Atlantic salmon

et al. 2010

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“…In contrast, many complex traits studied in genetics have markedly non-normal distributions (Micceri 1989; Allison et al 1999), which in many cases implies non-normal residuals. Several approaches exist to respond to non-normality, including but not limited to reliance on asymptotic properties (Mehta et al 2004), transformation of the data (Etzel et al 2003; George and Elston 1987; Shete et al 2004; Yang et al 2006), and the use of nonparametric tests (Neave and Wothington 1989), which subsumes the analysis of rank data (e.g., Zak et al 2007), permutation tests, and bootstrap approaches as special cases (Good 1999). …”

Section: Introductionmentioning

confidence: 99%

Rank-Based Inverse Normal Transformations are Increasingly Used, But are They Merited?

2009

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Many complex traits studied in genetics have markedly non-normal distributions. This often implies that the assumption of normally distributed residuals has been violated. Recently, inverse normal transformations (INTs) have gained popularity among genetics researchers and are implemented as an option in several software packages. Despite this increasing use, we are unaware of extensive simulations or mathematical proofs showing that INTs have desirable statistical properties in the context of genetic studies. We show that INTs do not necessarily maintain proper Type 1 error control and can also reduce statistical power in some circumstances. Many alternatives to INTs exist. Therefore, we contend that there is a lack of justification for performing parametric statistical procedures on INTs with the exceptions of simple designs with moderate to large sample sizes, which makes permutation testing computationally infeasible and where maximum likelihood testing is used. Rigorous research evaluating the utility of INTs seems warranted.

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“…Given that quantitative trait loci mapping assumes normal phenotypic distributions, these phenotypes were normalized by using the Box-Cox method (Figures 3b,d and f). 25 The distributions of the transformed data resembled a normal distribution more closely than those of the raw data (P = 0.03424, 0.0002131 and 0.04858). Viral titer in the liver was significantly correlated with serum ALT (R 2 = 0.44), and also with heart viral titer but to a lesser degree (R 2 = 0.30).…”

Section: Mice Of the Bca86 Rc Strain Succumb To Lethal Cvb3 Infectionmentioning

confidence: 82%

Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis

et al. 2015

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The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis. Twenty-five AcB/BcA recombinant congenic mouse strains were screened. One, BcA86, was found to be particularly susceptible to early mortality; 100% of BcA86 mice died by day 6 compared with 0% of B6 mice (P=0.0012). This increased mortality was accompanied by an increased hepatic necrosis as measured by serum alanine aminotransferase (ALT) levels (19547±10556 vs 769±109, P=0.0055). This occurred despite a predominantly resistant (C57BL/6) genetic background. Linkage analysis in a cohort (n=210) of (BcA86x C56Bl/10)F2 animals revealed a new locus on chromosome 13 (peak linkage 101.2 Mbp, lod 4.50 and P=0.003). This locus controlled serum ALT levels as early as 48 h following the infection, and led to an elevated expression of type I interferon. Another locus on chromosome 17 (peak linkage 57.2 Mbp) was significantly linked to heart viral titer (lod 3.4 and P=0.046). These results provide new evidence for the presence of genetic loci contributing to the susceptibility of mice to viral hepatitis.

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Box–Cox transformation for QTL mapping

Cited by 19 publications

References 21 publications

Discovery and application of insertion-deletion (INDEL) polymorphisms for QTL mapping of early life-history traits in Atlantic salmon

Discovery and application of insertion-deletion (INDEL) polymorphisms for QTL mapping of early life-history traits in Atlantic salmon

Rank-Based Inverse Normal Transformations are Increasingly Used, But are They Merited?

Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis

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