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1.
Conditioning on subsets of the data: applications to ascertainment and other genetic problems. 总被引:3,自引:3,他引:0 下载免费PDF全文
S E Hodge 《American journal of human genetics》1988,43(4):364-373
I here consider the question of when to formulate a likelihood over the whole data set, as opposed to conditioning the likelihood on subsets of the data (i.e., joint vs. conditional likelihoods). I show that when certain conditions are met, these two likelihoods are guaranteed to be equivalent, and thus that it is generally preferable to condition on subsets, since that likelihood is mathematically and computationally simpler. However, I show that when these conditions are not met, conditioning on subsets of the data is equivalent to introducing additional df into our genetic model, df that we may not have been aware of. I discuss the implications of these facts for ascertainment corrections and other genetic problems. 相似文献
2.
The effects of a known family-size distribution on the estimation of genetic parameters. 总被引:1,自引:1,他引:0 下载免费PDF全文
We consider the question: In a segregation analysis, can knowledge of the family-size distribution (FSD) in the population from which a sample is drawn improve the estimators of genetic parameters? In other words, should one incorporate the population FSD into a segregation analysis if one knows it? If so, then under what circumstances? And how much improvement may result? We examine the variance and bias of the maximum likelihood estimators both asymptotically and in finite samples. We consider Poisson and geometric FSDs, as well as a simple two-valued FSD in which all families in the population have either one or two children. We limit our study to a simple genetic model with truncate selection. We find that if the FSD is completely specified, then the asymptotic variance of the estimator may be reduced by as much as 5%-10%, especially when the FSD is heavily skewed toward small families. Results in small samples are less clear-cut. For some of the simple two-valued FSDs, the variance of the estimator in small samples of one- and two-child families may actually be increased slightly when the FSD is included in the analysis. If one knows only the statistical form of the FSD, but not its parameter, then the estimator is improved only minutely. Our study also underlines the fact that results derived from asymptotic maximum likelihood theory do not necessarily hold in small samples. We conclude that in most practical applications it is not worth incorporating the FSD into a segregation analysis. However, this practice may be justified under special circumstances where the FSD is completely specified, without error, and the population consists overwhelmingly of small families. 相似文献
3.
DNA sequence analysis of a 5.27-kb direct repeat occurring adjacent to the regions of S-episome homology in maize mitochondria. 总被引:8,自引:1,他引:7 下载免费PDF全文
J P Houchins H Ginsburg M Rohrbaugh R M Dale C L Schardl T P Hodge D M Lonsdale 《The EMBO journal》1986,5(11):2781-2788
The DNA sequence of the 5270-bp repeated DNA element from the mitochondrial genome of the fertile cytoplasm of maize has been determined. The repeat is a major site of recombination within the mitochondrial genome and sequences related to the R1(S1) and R2(S2) linear episomes reside immediately adjacent to the repeat. The terminal inverted repeats of the R1 and R2 homologous sequences form one of the two boundaries of the repeat. Frame-shift mutations have introduced 11 translation termination codons into the transcribed S2/R2 URFI gene. The repeated sequence, though recombinantly active, appears to serve no biological function. 相似文献
4.
Growth of Chikungunya Virus in Baby Hamster Kidney Cell (BHK-21-Clone 13) Suspension Cultures 总被引:2,自引:2,他引:0 下载免费PDF全文
This report describes the methods used to obtain high titers of chikungunya virus with suspension cultures of BHK-21-clone 13 cells. The cells were grown at 37 C to a cell concentration of 10(6) to 2 x 10(6) per ml. After maximum cell growth, the cells were inoculated with chikungunya virus at a multiplicity of 1 to 2 50% suckling mouse intracerebral lethal doses (SMICLD(50)) per cell in the spent Eagle's minimum essential medium for suspension cultures (MEMS), or the cell cultures were centrifuged at 200 x g and resuspended in either fresh MEMS or medium 199 prior to inoculation. The medium used had no effect on virus titer. The inoculated cultures were incubated at 34 C until the cell viability dropped to 30%, which usually occurred 28 to 30 hr postinoculation. After these procedures, chikungunya virus titers of log(10) 10.3 to 11.8 SMICLD(50) per ml were obtained. 相似文献
5.
The Habsburg jaw 总被引:3,自引:0,他引:3
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A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed 总被引:8,自引:0,他引:8
K Li C K Warner J A Hodge S Minoshima J Kudoh R Fukuyama M Maekawa Y Shimizu N Shimizu D C Wallace 《The Journal of biological chemistry》1989,264(24):13998-14004
9.
This paper investigates effects on lod scores when one individual in a data set changes diagnostic or recombinant status. First we examine the situation in which a single offspring in a nuclear family changes status. The nuclear-family situation, in addition to being of interest in its own right, also has general theoretical importance, since nuclear families are "transparent"; that is, one can track genetic events more precisely in nuclear families than in complex pedigrees. We demonstrate that in nuclear families log10 [(1-theta)/theta] gives an upper limit on the impact that a single offspring's change in status can have on the lod score at that recombination fraction (theta). These limits hold for a fully penetrant dominant condition and fully informative marker, in either phase-known or phase-unknown matings. Moreover, log10 [(1-theta)/theta] (where theta denotes the value of theta at which Zmax occurs) gives an upper limit on the impact of a single offspring's status change on the maximum lod score (Zmax). In extended pedigrees, in contrast to nuclear families, no comparable limit can be set on the impact of a single individual on the lod score. Complex pedigrees are subject to both stabilizing and destabilizing influences, and these are described. Finally, we describe a "sensitivity analysis," in which, after all linkage analysis is completed, every informative individual in the data set is changed, one at a time, to see the effect which each separate change has on the lod scores. The procedure includes identifying "critical individuals," i.e., those who would have the greatest impact on the lod scores, should their diagnostic status in fact change. To illustrate use of the sensitivity analysis, we apply it to the large bipolar pedigree reported by Egeland et al. and Kelsoe et al. We show that the changes in lod scores observed there, on the order of 1.1-1.2 per person, are not unusual. We recommend that investigators include a sensitivity analysis as a standard part of reporting the results of a linkage analysis. 相似文献
10.