In Silico Genetics: Identification of a Functional Element Regulating
            <i>H2</i>
            -
            <i>E</i>
            α Gene Expression

Liao, Guochun; Wang, Jianmei; Guo, Jingshu; Allard, John; Cheng, Janet; Ng, Anh; Shafer, Steven L.; Puech, Anne; Mcpherson, John Douglas; Foernzler, Dorothee; Peltz, Gary; Usuka, Jonathan

doi:10.1126/science.1100636

Cited by 111 publications

(139 citation statements)

References 12 publications

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“…As a result, associating breedspecific genotypes with ''fixed'' phenotypes in multiple breeds (across-breed mapping) presents a powerful tool for identifying quantitative trait loci (QTL) that may form the genetic basis for the phenotypic diversity observed in dog breeds. Similar approaches have been described using inbred mouse strains (Grupe et al 2001;Liao et al 2004;Pletcher et al 2004;Wang et al 2005), and these have 1 been combined with classical QTL analysis (Park et al 2003;Dipetrillo et al 2004;Wang et al 2004;Cervino et al 2005). However, the number of inbred mouse lines available are far fewer than the number of dog breeds, and the number of phenotypes offered by mice much fewer than what is offered by the nearly 300 breeds of domestic dog.…”

mentioning

confidence: 99%

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

Jones¹,

Chase

Martin³

et al. 2008

Genetics

143

168

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Phenotypic stereotypes are traits, often polygenic, that have been stringently selected to conform to specific criteria. In dogs, Canis familiaris, stereotypes result from breed standards set for conformation, performance (behaviors), etc. As a consequence, phenotypic values measured on a few individuals are representative of the breed stereotype. We used DNA samples isolated from 148 dog breeds to associate SNP markers with breed stereotypes. Using size as a trait to test the method, we identified six significant quantitative trait loci (QTL) on five chromosomes that include candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Less well-documented data for behavioral stereotypes tentatively identified loci for herding, pointing, boldness, and trainability. Four significant loci were identified for longevity, a breed characteristic not under direct selection, but inversely correlated with breed size. The strengths and limitations of the approach are discussed as well as its potential to identify loci regulating the within-breed incidence of specific polygenic diseases.

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mentioning

confidence: 99%

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

Jones¹,

Chase

Martin³

et al. 2008

Genetics

143

168

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“…This method can be directly applied to inbred strains of mice. When haplotype data are available, the new method can further be extended to haplotype-based MLISM (Liao et al, 2004;Guo et al, 2006Guo et al, , 2007Liang et al, 2006a, b). When single-nucleotide polymorphism molecular data are available, the new method can be used to improve the precision of QTL mapping and to select the candidate genes.…”

Section: Discussionmentioning

confidence: 99%

“…Chesler et al (2001) and Darvasi (2001) have questioned the validity of this so-called in silico mapping (ISM) on the basis that it is associated with a relatively high false-positive rate (FPR). Recently, Peltz's group further extended the computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks, known as the haplotype-based ISM (HISM) approach (Liao et al, 2004). This method predicted the genetic basis for strain-specific differences in several biologically important traits of mice (Liao et al, 2004;Guo et al, 2006Guo et al, , 2007Liang et al, 2006a, b), but it only performs a single-locus analysis.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Peltz's group further extended the computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks, known as the haplotype-based ISM (HISM) approach (Liao et al, 2004). This method predicted the genetic basis for strain-specific differences in several biologically important traits of mice (Liao et al, 2004;Guo et al, 2006Guo et al, , 2007Liang et al, 2006a, b), but it only performs a single-locus analysis. Nevertheless, the advantages of detecting QTL from inbred strains without the need for conventional QTL analysis are strong enough to justify seeking improvements to the ISM methodology.…”

Section: Introductionmentioning

confidence: 99%

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Multiple loci in silico mapping in inbred lines

Lü

et al. 2009

Heredity

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The in silico mapping (ISM) technique and its extension represent major advances for novel gene discovery in germplasm resources of inbred lines. However, the techniques suffer from a relatively high false-positive rate (FPR) and they do not consider the effect of linkage disequilibrium (LD) markers around the identified quantitative trait locus (QTL). In addition, it has not yet been established whether it is optimal to use absolute trait differences as the response variable. To address these problems, this article presents the multiple loci ISM (MLISM) approach, which uses all markers on the entire genome, along with a penalized maximum likelihood. The method proposed here was verified by a series of simulation experiments with a maize pedigree population of inbred lines of known ancestry. Results from the simulated studies show that the best response variable is the trait product. The MLISM FPR is substantially decreased and the proportion of the number of false QTL to the number of LD markers around the identified QTL is adequately reduced. The MLISM method, with the trait product as the response variable, is an improvement on the existing methods for novel QTL mapping in germplasm resources of inbred lines.

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“…There are many new methods for mapping QTL and isolating the specific genes of importance. Inbred strains can be surveyed directly for associations between markers and phenotypes (Grupe et al 2001;Liao et al 2004), although the statistical mapping power of such analyses has been questioned due to the close pedigree relationships among standard inbred strains, leading to large haplotype similarities. Mapping studies are more difficult, but more powerful, in outbred stocks (Mott et al 2000;Flint et al 2005;Valdar et al 2006).…”

Section: Inbred Strainsmentioning

confidence: 99%

Neurogenetic studies of alcohol addiction

Crabbe

2008

Phil. Trans. R. Soc. B

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Neurogenetic studies of alcohol dependence have relied substantially on genetic animal models, particularly rodents. Studies of inbred strains, selectively bred lines and mutants bearing genes whose function has been targeted for over or under expression are reviewed. Studies focused on gene expression changes are the most recent contributors to this literature, and some genetic effects may work through epigenetic mechanisms. In a few instances, interesting parallels have been revealed between genetic risk in humans and studies in non-human animal models. Future approaches are likely to be increasingly complex.

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In Silico Genetics: Identification of a Functional Element Regulating H2 - E α Gene Expression

Cited by 111 publications

References 12 publications

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

Multiple loci in silico mapping in inbred lines

Neurogenetic studies of alcohol addiction

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