New mathematical methods in human gene mapping
Three published papers are presented. The first paper consists of an analytical investigation of the effects of marker heterozygosity and intermarker distance on a linkage analysis with a disease gene. The goal of this paper was to determine optimal properties for a putative genome-spanning map of markers. The results showed, as expected, that the power is highest when marker heterozygosity is highest, and/or intermarker distance is smallest. However, the authors found that the expected length of the one-lod-unit support interval was almost exclusively dependent on intermarker distance. The second paper deals with a repeated subsampling strategy I developed based on the multisample bootstrap of Efron (1982). This technique allows the user to perform a normally computationally intensive simulation study in a dramatically shorter time. In the example discussed in the paper, determining the p-value of a maximized-over-models maximum lod score, the computer time required for the study was reduced from several weeks to a few hours. This statistical method has subsequently been applied to other problems by Maclean et al. (1992), Leal et al. (1993), and Kong et al. (1992), for example. In the final paper, a novel variation of the haplotype relative risk (HRR) statistic of Rubinstein et al. (1981) is presented. This method, like the original HRR allows one to construct a well-matched control sample from the non-transmitted alleles of the parents of an affected child. In the statistic, the two alleles transmitted to the child constitute two observations in the [open quotes]case[close quotes] sample, and the two alleles the parents did not transmit from the [open quotes]control[close quotes] sample. The relationship between the projects is outlined in the introduction to this thesis, as is the general scientific background which led to the implementation and development of this research.
- Research Organization:
- Columbia Univ., New York, NY (United States)
- OSTI ID:
- 5215973
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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