Haplotype Structure of the Mouse Genome

Wang, Jianmei; Liao, Guochun; Cheng, Janet; Nguyen, Anh V.; Guo, Jingshu; Chou, Christopher; Hu, Steve; Jiang, Sharon; Allard, John; Shafer, Steven L.; Puech, Anne; Mcpherson, John Douglas; Foernzler, Dorothee; Peltz, Gary; Usuka, Jonathan

doi:10.1007/978-1-59259-930-1_4

Cited by 9 publications

(11 citation statements)

References 10 publications

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“…Conventional QTL studies use the progeny or recombinant inbred strains deriving from only two founding strains. The use of a broader panel of strains potentially allows the identification of a larger number of genetic factors influencing bone-related traits in mice [53,54]. Second, we had available a large SNP database providing relatively high power to detect associations with 10 Mbp genomic segments [43].…”

Section: Discussionmentioning

confidence: 99%

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Sabsovich

Clark

Liao³

et al. 2008

Bone

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MicroCT analysis of 12 inbred strains of mice identified 5 novel chromosomal regions influencing skeletal phenotype. Bone morphology varied in a compartment-and site-specific fashion across strains and genetic influences contributed to the morphometric similarities observed in femoral and vertebral bone within the trabecular bone compartment.Introduction-Skeletal development is known to be regulated by both heritable and environmental factors, but whether genetic influence on peak bone mass is site-or compartment-specific is unknown. This study examined the genetic variation of cortical and trabecular bone microarchitecture across 12 strains of mice.

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Section: Discussionmentioning

confidence: 99%

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Sabsovich

Clark

Liao³

et al. 2008

Bone

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“…11,12 In brief, a haplotype block map of the mouse genome was constructed, and single-nucleotide polymorphisms (SNPs) were organized into haplotype blocks, which typically consisted of 2-4 haplotypes. 13,14 The haplotype-based computational analysis identified haplotype blocks in which the haplotypic strain grouping within the block correlates with the distribution of phenotypic data among the inbred strains analyzed. The program calculates a P-value, which assesses the likelihood that genetic variation within each block could underlie the observed distribution of phenotypes among the inbred strains.…”

Section: Computational Genetic Mappingmentioning

confidence: 99%

“…We recently described how in vivo pharmacokinetic studies 9 or a hepatic in vitro drug biotransformation system 10 could be used in conjunction with haplotype-based computational genetic analysis [11][12][13][14] to quickly identify genetic factors affecting the metabolism of commonly prescribed drugs in mice. To do this, a test drug is administered to multiple inbred strains, or incubated with hepatic extracts in vitro, and then individual drug metabolites are measured at multiple time points.…”

Section: Introductionmentioning

confidence: 99%

In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor

Zhang¹,

Liu

Weller³

et al. 2010

Pharmacogenomics J

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The clinical development of a candidate p38 kinase inhibitor was terminated because of its unexpectedly rapid clearance in human subjects. Its short halflife and metabolic profile in human beings were vastly different from that in rats, dogs, and monkeys characterized during routine pre-clinical studies. Mice generated the predominant drug (4-hydroxylated) metabolite produced in human beings, which was not found in other species. The data from a murine in vitro drug biotransformation assay that used liver extracts from 14 inbred mouse strains were analyzed by haplotype-based computational genetic analysis. This led to the identification of aldehyde oxidase-1 (AOX1) as the enzyme responsible for the rapid metabolism of this drug. Specific enzyme inhibitors and expressed recombinant enzymes were used to confirm that AOX catalyzed the formation of the 4-hydroxylated drug metabolite in mouse and man. Genetic variation within Aox1 regulated the level of hepatic Aox1 mRNA, AOX1 protein, and enzyme activity among the inbred strains. Thus, computational murine pharmacogenetic analysis can facilitate the identification and characterization of drug metabolism pathways that are differentially utilized by humans and other species.

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“…In brief, a haplotype block map of the mouse genome was constructed, and single-nucleotide polymorphisms (SNPs) were organized into haplotype blocks that typically consisted of 2-4 haplotypes (29,30). The haplotype-based computational analysis identified haplotype blocks in which the haplotypic strain grouping within the block correlates with the distribution of phenotypic data among the inbred strains analyzed.…”

Section: Computational Genetic Mappingmentioning

confidence: 99%

Genetic Susceptibility to the Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Is MHC Dependent

Tregoning

Yamaguchi

Wang

et al. 2010

The Journal of Immunology

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Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity, resulting in hospitalization for bronchiolitis in some infected infants that is associated with wheeze in later life. Genetic factors are known to affect the severity of the sequelae after RSV infection, but the complexity of the temporal and genetic effects makes it difficult to analyze this response in studies in man. Therefore, we developed a murine genetic model to analyze the sequelae occurring after RSV infection in early life. Haplotype-based genetic analysis of interstrain differences in severity identified the MHC as an important genetic determinant. This was confirmed by analysis of responses in congenic mice with different MHC haplotypes. We also found that susceptible strains had high CD8 levels during secondary infection. Analysis of first filial generation, second filial generation, and back-cross progeny produced by intercrossing resistant (H-2k, C3H/HeN) and sensitive (H-2b, BALB/c) strains indicated that susceptibility to sequelae after RSV infection was dominantly inherited but also segregated in a non-MHC–dependent manner. Thus, MHC haplotype and its effect on CD8 cell response is an important determinant of the outcome of neonatal RSV infection.

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Haplotype Structure of the Mouse Genome

Cited by 9 publications

References 10 publications

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

Bone microstructure and its associated genetic variability in 12 inbred mouse strains: μCT study and in silico genome scan

In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor

Genetic Susceptibility to the Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Is MHC Dependent

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