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  • 1
    Electronic Resource
    Electronic Resource
    Network models for sequence evolution (1993)
    Springer
    Journal of molecular evolution 37 (1993), S. 77-85 
    Details
    ISSN: 1432-1432
    Keywords: Convergent evolution ; Gene conversion ; Maximum likelihood ; Phylogeny ; Quasi-species ; Recombination ; Substitution rate ; Virus evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We introduce a general class of models for sequence evolution that includes network phylogenies. Networks, a generalization of strictly tree-like phylogenies, are proposed to model situations where multiple lineages contribute to the observed sequences. An algorithm to compute the probability distribution of binary character-state configurations is presented and statistical inference for this model is developed in a likelihood framework. A stepwise procedure based on likelihood ratios is used to explore the space of models. Starting with a star phylogeny, new splits (nontrivial bipartitions of the sequence set) are successively added to the model until no significant change in the likelihood is observed. A novel feature of our approach is that the new splits are not necessarily constrained to be consistent with a treelike mode of evolution. The fraction of invariable sites is estimated by maximum likelihood simultaneously with other model parameters and is essential to obtain a good fit to the data. The effect of finite sequence length on the inference methods is discussed. Finally, we provide an illustrative example using aligned VPl genes from the foot and mouth disease viruses (FMDV). The different serotypes of the FMDV exhibit a range of treelike and network evolutionary relationships.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170465
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  • 2
    Electronic Resource
    Electronic Resource
    Sequential Quantitative Trait Locus Mapping in Experimental Crosses (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Statistical applications in genetics and molecular biology 6.2007, 1, art12 
    Details
    ISSN: 1544-6115
    Source: Berkeley Electronic Press Academic Journals
    Topics: Biology
    Notes: The etiology of complex diseases is heterogeneous. The presence of risk alleles in one or more genetic loci affects the function of a variety of intermediate biological pathways, resulting in the overt expression of disease. Hence, there is an increasing focus on identifying the genetic basis of disease by systematically studying phenotypic traits pertaining to the underlying biological functions. In this paper we focus on identifying genetic loci linked to quantitative phenotypic traits in experimental crosses. Such genetic mapping methods often use a one stage design by genotyping all the markers of interest on the available subjects. A genome scan based on single locus or multi-locus models is used to identify the putative loci. Since the number of quantitative trait loci (QTLs) is very likely to be small relative to the number of markers genotyped, a one-stage selective genotyping approach is commonly used to reduce the genotyping burden, whereby markers are genotyped solely on individuals with extreme trait values. This approach is powerful in the presence of a single quantitative trait locus (QTL) but may result in substantial loss of information in the presence of multiple QTLs. Here we investigate the efficiency of sequential two stage designs to identify QTLs in experimental populations. Our investigations for backcross and F2 crosses suggest that genotyping all the markers on 60% of the subjects in Stage 1 and genotyping the chromosomes significant at 20% level using additional subjects in Stage 2 and testing using all the subjects provides an efficient approach to identify the QTLs and utilizes only 70% of the genotyping burden relative to a one stage design, regardless of the heritability and genotyping density. Complex traits are a consequence of multiple QTLs conferring main effects as well as epistatic interactions. We propose a two-stage analytic approach where a single-locus genome scan is conducted in Stage 1 to identify promising chromosomes, and interactions are examined using the loci on these chromosomes in Stage 2. We examine settings under which the two-stage analytic approach provides sufficient power to detect the putative QTLs.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/sagmb/vol6/iss1/art12
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  • 3
    Electronic Resource
    Electronic Resource
    Transformations for cDNA Microarray Data (2003)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Statistical applications in genetics and molecular biology 2.2003, 1, art4 
    Details
    ISSN: 1544-6115
    Source: Berkeley Electronic Press Academic Journals
    Topics: Biology
    Notes: Two channel microarray data often contain systematic variations that can be minimized by data transformation prior to further analysis. The most commonly observed effects are revealed by viewing scatter plots of the logarithm of the ratio by the average logarithmic intensity of the two color channels (RI plots). In this paper we present a general model for signal intensity data with multiple error sources. We demonstrate how these sources of error influence the shape of an RI plot. We then compare some currently available transformation strategies in terms of their mechanism and performance on both simulated and real microarray data. A linlog transformation is proposed to stabilize the variance of the log ratios. We also propose a regional smoothing method to remove variation in log ratios due to spatial heterogeneity on the microarray surface. The discussed transformations represent an important initial step in microarray data analysis for both ratio-based and ANOVA methods.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/sagmb/vol2/iss1/art4
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  • 4
    Electronic Resource
    Electronic Resource
    On the subspecific origin of the laboratory mouse (2007)
    [s.l.] : Nature Publishing Group
    Nature genetics 39 (2007), S. 1100-1107 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The genome of the laboratory mouse is thought to be a mosaic of regions with distinct subspecific origins. We have developed a high-resolution map of the origin of the laboratory mouse by generating 25,400 phylogenetic trees at 100-kb intervals spanning the genome. On average, 92% of the genome is ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng2087
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  • 5
    Electronic Resource
    Electronic Resource
    Stochastic models for heterogeneous DNA sequences (1989)
    Springer
    Bulletin of mathematical biology 51 (1989), S. 79-94 
    Details
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The composition of naturally occurring DNA sequences is often strikingly heterogeneous. In this paper, the DNA sequence is viewed as a stochastic process with local compositional properties determined by the states of a hidden Markov chain. The model used is a discrete-state, discreteoutcome version of a general model for non-stationary time series proposed by Kitagawa (1987). A smoothing algorithm is described which can be used to reconstruct the hidden process and produce graphic displays of the compositional structure of a sequence. The problem of parameter estimation is approached using likelihood methods and an EM algorithm for approximating the maximum likelihood estimate is derived. The methods are applied to sequences from yeast mitochondrial DNA, human and mouse mitochondrial DNAs, a human X chromosomal fragment and the complete genome of bacteriophage lambda.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02458837
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  • 6
    Electronic Resource
    Electronic Resource
    Characterization of human embryonic stem cell lines by the International Stem Cell Initiative (2007)
    [s.l.] : Nature Publishing Group
    Nature biotechnology 25 (2007), S. 803-816 
    Details
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nbt1318
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  • 7
    Electronic Resource
    Electronic Resource
    Fundamentals of experimental design for cDNA microarrays (2002)
    [s.l.] : Nature Publishing Group
    Nature genetics 32 (2002), S. 490-495 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Microarray technology is now widely available and is being applied to address increasingly complex scientific questions. Consequently, there is a greater demand for statistical assessment of the conclusions drawn from microarray experiments. This review discusses fundamental issues of how to design ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng1031
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  • 8
    Electronic Resource
    Electronic Resource
    Variation in gene expression within and among natural populations (2002)
    [s.l.] : Nature Publishing Group
    Nature genetics 32 (2002), S. 261-266 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Evolution may depend more strongly on variation in gene expression than on differences between variant forms of proteins. Regions of DNA that affect gene expression are highly variable, containing 0.6% polymorphic sites. These naturally occurring polymorphic nucleotides can alter in vivo ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng983
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  • 9
    Electronic Resource
    Electronic Resource
    Sex, flies and microarrays (2001)
    [s.l.] : Nature Publishing Group
    Nature genetics 29 (2001), S. 355-356 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Gene expression microarrays generate stunningly large data sets that require many hours of staring at overwhelmingly long spreadsheets and the frequent purchase of more RAM for laboratory computers. When designing a gene expression experiment, however, perhaps one should imagine that only a single ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng1201-355
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  • 10
    Electronic Resource
    Electronic Resource
    Quantitative trait loci for bone density in C57BL/6J and CAST/EiJ inbred mice (1999)
    Springer
    Mammalian genome 10 (1999), S. 1043-1049 
    Details
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Genetic analyses for loci regulating bone mineral density have been conducted in a cohort of F2 mice derived from intercross matings of (C57BL/6J × CAST/EiJ)F1 parents. Femurs were isolated from 714 4-month-old females when peak adult bone density had been achieved. Bone mineral density (BMD) data were obtained by peripheral quantitative computed tomography (pQCT), and genotype data were obtained by Polymerase Chain Reaction (PCR) assays for polymorphic markers carried in genomic DNA of each mouse. Genome-wide scans for co-segregation of genetic marker data with high or low BMD revealed loci on eight different chromosomes, four of which (Chrs 1, 5, 13, and 15) achieved conservative statistical criteria for suggestive, significant, or highly significant linkage with BMD. These four quantitative trait loci (QTLs) were confirmed by a linear regression model developed to describe the main effects; none of the loci exhibited significant interaction effects by ANOVA. The four QTLs have been named Bmd1 (Chr 1), Bmd2 (Chr 5), Bmd3 (Chr 13), and Bmd4 (Chr 15). Additive effects were observed for Bmd1, recessive for Bmd3, and dominant effects for Bmd2 and Bmd4. The current large size of the QTL regions (6→31 cM) renders premature any discussion of candidate genes at this time. Fine mapping of these QTLs is in progress to refine their genetic positions and to evaluate human homologies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003359901159
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