Showing papers by "Michael Boehnke published in 1995"
TL;DR: A model of fragment generation and retention for data involving two or more copies of the chromosome of interest per clone is presented and statistical criteria such as minimum obligate breaks, maximum likelihood ratios, and Bayesian posterior probabilities can be used to decide locus order.
Abstract: Radiation hybrid mapping is a somatic cell technique for ordering genetic loci along a chromosome and estimating physical distances between adjacent loci. This paper presents a model of fragment generation and retention for data involving two or more copies of the chromosome of interest per clone. Such polyploid data can be generated by initially irradiating normal diploid cells or by pooling haploid or diploid clones. The current model assumes that fragments are generated in the ancestral cell of a clone according to an independent Poisson breakage process along each chromosome. Once generated, fragments are independently retained in the clone with a common retention probability. On the basis of this and less restrictive retention models, statistical criteria such as minimum obligate breaks, maximum likelihood ratios, and Bayesian posterior probabilities can be used to decide locus order. Distances can be estimated by maximum likelihood. Likelihood computation is particularly challenging, and computing techniques from the theory of hidden Markov chains prove crucial. Within this context it is possible to incorporate typing errors. The statistical tools discussed here are applied to 14 loci on the short arm of human chromosome 4.
170 citations
TL;DR: It is found that in general, combinations of ploidy and chromosome-specific retention rates that lead to a per-hybrid retention rate of approximately 50% result in the greatest power to order markers, and analyzing polyploid radiation hybrids as if they were haploid does not compromise the ability to order marker but does result in less accurate intermarker distance estimates.
Abstract: In this paper we consider issues of experimental design and error detection and correction for polyploid radiation hybrid mapping. Using analytic methods and computer simulation, we first consider the combinations of fragment retention rate, ploidy, and marker spacing that provide the best chance to order markers. We find that in general, combinations of ploidy and chromosome-specific retention rates that lead to a per-hybrid retention rate of -50% result in the greatest power to order markers. We also find that analyzing polyploid radiation hybrids as if they were haploid does not compromise the ability to order markers but does result in less accurate intermarker distance estimates. Second, we examine the effect of typing errors on two-locus information, ability to order multiple loci, and estimation of intermarker distances and total map length. Even low levels of error result in large losses of information about breakage probabilities, markedly reduce ability to order loci, and inflate estimates of intermarker distances and total map length. We compare the ordering accuracy that results from duplicate typing of hybrids to that of single typing twice as many hybrids and find that duplicate typing results in a higher probability of identifying the true order as one of the best orders, but that single typing of twice as many hybrids results in stronger support for the true order. For low error rates, framework maps constructed from the larger single-typed panels are only slightly less likely to be correct and include substantially more markers than the smaller double-typed panels. Third, we develop a method to calculate the distribution of the number of obligate chromosome breaks for a polyploid radiation hybrid under a given locus order and discuss how this method may be used to identify hybrids with suspiciously large numbers of chromosome breaks.
49 citations
TL;DR: This study moves the RS centromeric boundary to (AFM291wf5, DXS443), about 5.5 cM closer than the previously reported boundary at DXS274 and narrows the RS inclusion interval to about 3.7 cM (using distances from CEPH family data).
Abstract: Juvenile X-linked retinoschisis (RS) is an eye disease that causes acuity reduction and peripheral visual field loss typically beginning early in life. In further work towards positional cloning of th
8 citations
TL;DR: The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosome 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3).
Abstract: The human homolog of the Saccharomyces cerevisiae cell division control 27 gene (CDC27) was mapped to human chromosome 17q12-q21 using a panel of human/rodent somatic cell hybrids and localized distal to the breast cancer susceptibility gene, BRCA1, using a panel of radiation hybrids. The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosomes 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3). Further confirmation of this localization comes from the sequence tagged site (STS) mapping of human CDC27 to the same yeast artificial chromosomes (YACs) positive for ITGB3. The estimated distance between ITGB3 and human CDC27 is less than 600 kb.
1 citations