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  • 1
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    In silico mapping of complex disease-related traits in mice (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-06-09
    Description: Experimental murine genetic models of complex human disease show great potential for understanding human disease pathogenesis. To reduce the time required for analysis of such models from many months down to milliseconds, a computational method for predicting chromosomal regions regulating phenotypic traits and a murine database of single nucleotide polymorphisms were developed. After entry of phenotypic information obtained from inbred mouse strains, the phenotypic and genotypic information is analyzed in silico to predict the chromosomal regions regulating the phenotypic trait.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grupe, A -- Germer, S -- Usuka, J -- Aud, D -- Belknap, J K -- Klein, R F -- Ahluwalia, M K -- Higuchi, R -- Peltz, G -- 1 R01 HG02322-01/HG/NHGRI NIH HHS/ -- R01 AR044659/AR/NIAMS NIH HHS/ -- R01 AR044659-07/AR/NIAMS NIH HHS/ -- T32HG-00044/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1915-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomics, Roche Bioscience, Palo Alto, CA 94303, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397946" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Bone Density ; Chromosome Mapping/*methods ; Crosses, Genetic ; Databases, Factual ; *Disease Models, Animal ; Female ; Genetic Linkage ; Genotype ; Humans ; Linkage Disequilibrium ; Major Histocompatibility Complex/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Phenotype ; Polymerase Chain Reaction ; *Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Software
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Regulation of bone mass in mice by the lipoxygenase gene Alox15 (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-13
    Description: The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development. Pharmacologic inhibitors of this enzyme improved bone density and strength in two rodent models of osteoporosis. These results suggest that drugs targeting the 12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, Robert F -- Allard, John -- Avnur, Zafrira -- Nikolcheva, Tania -- Rotstein, David -- Carlos, Amy S -- Shea, Marie -- Waters, Ruth V -- Belknap, John K -- Peltz, Gary -- Orwoll, Eric S -- AR44659/AR/NIAMS NIH HHS/ -- HG02322/HG/NHGRI NIH HHS/ -- R01 AR044659/AR/NIAMS NIH HHS/ -- R01 AR044659-08/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):229-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bone and Mineral Research Unit, Department of Medicine, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA. kleinro@ohsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716014" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonate 12-Lipoxygenase/*genetics/*metabolism ; Arachidonate 15-Lipoxygenase/*genetics/*metabolism ; Bone Density/drug effects/*genetics ; Bone Marrow Cells/metabolism ; Cell Differentiation ; Cells, Cultured ; Crosses, Genetic ; Enzyme Inhibitors/pharmacology ; Female ; Fluorenes/pharmacology ; Gene Expression Profiling ; Genetic Linkage ; Kidney/metabolism ; Lipoxygenase Inhibitors ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Knockout ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; Osteoblasts/cytology/metabolism/physiology ; Osteogenesis ; Osteoporosis/enzymology ; Polymorphism, Genetic ; Quantitative Trait Loci ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism ; Stromal Cells/metabolism ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    The D2 receptor gene (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crabbe, J C -- Belknap, J K -- Buck, K J -- New York, N.Y. -- Science. 1994 Oct 21;266(5184):352-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939673" target="_blank"〉PubMed〈/a〉
    Keywords: Alcoholism/genetics ; Animals ; Chromosome Mapping ; Mice ; Receptors, Dopamine D2/*genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Genetic animal models of alcohol and drug abuse (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-06-17
    Description: Behavioral and pharmacological responses of selectively bred and inbred rodent lines have been analyzed to elucidate many features of drug sensitivity and the adverse effects of drugs, the underlying mechanisms of drug tolerance and dependence, and the motivational states underlying drug reward and aversion. Genetic mapping of quantitative trait loci (QTLs) has been used to identify provisional chromosomal locations of genes influencing such pharmacological responses. Recent advances in transgenic technology, representational difference analysis, and other molecular methods now make feasible the positional cloning of QTLs that influence sensitivity to drugs of abuse. This marks a new period of synthesis in pharmacogenetic research, in which networks of drug-related behaviors, their underlying pharmacological, physiological, and biochemical mechanisms, and particular genomic regions of interest are being identified.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crabbe, J C -- Belknap, J K -- Buck, K J -- AA06243/AA/NIAAA NIH HHS/ -- AA08621/AA/NIAAA NIH HHS/ -- DA05228/DA/NIDA NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1994 Jun 17;264(5166):1715-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Service, Veterans Administration (VA) Medical Center, Portland, OR 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8209252" target="_blank"〉PubMed〈/a〉
    Keywords: Alcoholism/*genetics ; Animals ; Animals, Genetically Modified ; Chromosome Mapping ; *Disease Models, Animal ; Ethanol/pharmacology ; Genetic Techniques ; Mice ; Mice, Inbred Strains ; Oligonucleotides, Antisense/pharmacology ; Rats ; Rats, Inbred Strains ; Reward ; Substance-Related Disorders/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
    Electronic Resource
    Electronic Resource
    Genetic Commonalities between Ethanol-Induced LORR (Loss of Righting Reflex) and LORR due to Nitrous Oxide, Argon and Nitrogen (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 625 (1991), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1991.tb33890.x
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  • 6
    Electronic Resource
    Electronic Resource
    Chromosome Mapping of Gene Loci Affecting Morphine and Amphetamine Responses in BXD Recombinant Inbred Mice (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 654 (1992), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1992.tb25977.x
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  • 7
    Electronic Resource
    Electronic Resource
    Quantitative trait loci (QTL) applications to substances of abuse: Physical dependence studies with nitrous oxide and ethanol in BXD mice (1993)
    Springer
    Behavior genetics 23 (1993), S. 213-222 
    Details
    ISSN: 1573-3297
    Keywords: Quantitative trait loci (QTL) ; BXD ; recombinant inbred strains ; C57BL/6 ; DBA/2 ; nitrous oxide ; ethanol ; withdrawal syndromes ; chromosome mapping ; drug abuse ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci—those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01067426
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  • 8
    Electronic Resource
    Electronic Resource
    Differential neurosensitivity to three alcohols and phenobarbital in C57BL/6J and DBA/2J mice (1982)
    Springer
    Behavior genetics 12 (1982), S. 309-317 
    Details
    ISSN: 1573-3297
    Keywords: ethanol ; t-butanol ; phenobarbital ; 1,2-propanediol ; C57BL/6 ; DBA/2 ; inbred mice ; blood alcohol concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Neurosensitivity to ethanol, t-butanol, 1,2-propranediol, and phenobarbital was assessed in C57BL/6J and DBA/2J mice by means of the grid test, a measure of drug-induced ambulatory ataxia. In addition, blood and brain alcohol concentrations at the time of regaining the righting reflex were determined for ethanol and t-butanol. C57BL/6J mice were consistently more neurosensitive than DBA/2J mice to all four drugs on these two tests, but no strain difference was seen with regard to alcohol-induced hypothermia. These findings, and others reported in the literature, indicate that the strain differences in neurosensitivity are very much task dependent in that some measures yield no differences while other measures produce large differences between these two strains. Thus, one strain is not uniformly more sensitive to ethanol than the other across all measures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01067850
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  • 9
    Electronic Resource
    Electronic Resource
    Short-Term Selective Breeding as a Tool for QTL Mapping: Ethanol Preference Drinking in Mice (1997)
    Springer
    Behavior genetics 27 (1997), S. 55-66 
    Details
    ISSN: 1573-3297
    Keywords: Quantitative trait locus (QTL) ; C57BL/6J ; DBA/2J ; ethanol preference ; alcohol drinking ; gene mapping ; selective breeding ; mouse ; inbred strains
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Short-term selective breeding starting from an F2 intercross of two inbred strains is a largely unexploited but potentially useful tool for quantitative trait locus (QTL) mapping. The selection lines can also serve as a valuable confirmation test of recornbinant inbred (RI) QTL results when the same two progenitor strains are used. Starting from an F2 from a C57BL/6J (B6) × DBA/2J (D2) cross (B6D2F2), this approach was used in a population of ~72 mice per generation bidirectionally selected for two-bottle choice 10% ethanol (alcohol) preference for four generations. The high-preference line diverged significantly from the low line in the first generation with a realized heritabittty of .32. By generation 4, the preference ratios in the high line were double those seen in the low line. Regions of the genome previously implicated by BXD RI QTL analysis as containing QTLs were searched using microsatellite markers. The test for the presence of QTLs was based on the divergence of marker allele frequencies in the two oppositely selected lines significantly exceeding that expected from random (genetic) drift and allele frequency estimation error. Combining the BXD and two-way selection line results, the most probable QTL was found on chromosome 3 (near the AdhI locus; LOD ~2.9), other probable QTLs were found with LOD 2.4–2.6.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1025615409383
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  • 10
    Electronic Resource
    Electronic Resource
    Type I and type II error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains (1996)
    Springer
    Behavior genetics 26 (1996), S. 149-160 
    Details
    ISSN: 1573-3297
    Keywords: QTL mapping ; recombinant inbred strains ; C57BL/6 ; DBA/2 ; BXD
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Effective mapping strategies for quantitative traits must allow for the detection of the more important quantitative trait loci (QTLs) while minimizing false positives. Type I (false-positive) and Type II (false-negative) error rates were estimated from a computer simulation of QTL mapping in the BXD recombinant inbred (RI) set comprising 26 strains of mice, and comparisons made with theoretical predictions. The results are generally applicable to other RI sets when corrections are made for differing strain numbers and marker densities. Regardless of the number or magnitude of simulated QTLs contributing to the trait variance, thep value necessary to provide genome-wide. 05 Type I error protection was found to be aboutp=.0001. To provide adequate protection against both Type I (α=.0001) and Type II (β=.2) errors, a QTL would have to account for more than half of the between-strain (genetic) variance if the BXD or similar set was used alone. In contrast, a two-step mapping strategy was also considered, where RI strains are used as a preliminary screen for QTLs to be specifically tested (confirmed) in an F2 (or other) population. In this case, QTLs accounting for ∼16% of the between-strain variance could be detected with an 80% probability in the BXD set when α=0.2. To balance the competing goals of minimizing Type I and II errors, an economical strategy is to adopt a more stringent α initially for the RI screen, since this requires only a limited genome search in the F2 of the RI-implicated regions (∼10% of the F2 genome whenp〈.01 in the RIs). If confirmed QTLs do not account in the aggregate for a sufficient proportion of the genetic variance, then a more relaxed α value can be used in the RI screen to increase the statistical power. This flexibility in setting RI α values is appropriate only when adequate protection against Type I errors comes from the F2 (or other) confirmation test(s).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02359892
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