The effective population size (Ne) under marker-assisted selection (MAS) was considered in terms of the intrafamily (intraclass) correlation of selection criterion. It was shown that the effect of MAS on Ne depends not only on the phenotypic correlation (t) among family members but also on the genetic relationship (r) among family members. MAS with individual's phenotype and molecular score reduces Ne when t < r , and increases Ne when t > r , compared to the conventional selection on individual's phenotype alone. ln contrast, compared to the selection with phenotypic information from individual and family members, MAS using phenotypic and molecular information from individual and family members is expected to increase Ne when t < r , and has the reversed effect when t > r . Assuming a population consisting of full-sib families (r = 1⁄2), numerical computation and Monte Carlo simuation were carried out to illustrate and check the result.
Rapidly progressive glomerulonephritis (RPGN) is a life-theatening nephritis with a rapid decline in renal function. In this paper, we examine the three alternative treatments relative to the most commonly-used oral steroid for the two prevalent forms of RPGN, called PautiCrGN and MPA, in Japan. The response “Exitus” is potentially non-ignorably missing because the data were reported by those who administered the treatment. We use the method proposed in Ibrahim (1996) for estimating parameters in binomial logistic model when the missing response is potentially nonignorable. For PautiCrGN patients, we found that the three alternative treatments did not seem to affect the survival of the patients. MPA patients who underwent the steroidpulse or the cyclophosphamide with the oral steroid, seemed less likely to have survived compared with those who received the oral steroid only. For PautiCrGN patients, their exitus was not non-ignorably missing at first sight, and its missingness increased when the patients received the combined treatment. If, however, steroidpulse and/ or cyclophosphamide were additionally prescribed as the patients' conditions deteriorated, then the observed correlation above may prove the existence of non-ignorably missing exitus instead, because the exitus of serious patients might have been under-reported precisely because of their conditions.
Considering the situation where a cluster of QTLs (CQTLs) very tightly linked to each other are located on a chromosomal region marked by genetic markers, this paper concerns the best linear unbiased prediction of the random effects of CQTLs and those of the remaining QTLs unlinked to CQTLs for the genetic evaluation in outbred populations of animals. The proposed method incorporates the upstream as well as flanking marker information and utilizes the mixed model methodology. It is shown how the most appropriate values of the expectations ofthe identity-by-descent proportions, or EIBDPs, for gametes of animals to be evaluated can be calculated in the current case. With this method, the EIBDPs are used as the elements of the gametic relationship matrix. Using a small data-sample, the current method is demonstrated, being compared to the two previous alternative methods.
We present a maximum likelihood method based on composite interval mapping (CIM) for analyzing QTL in a mixed population composed of different F2 populations derived from diallel cross among several pure lines. A statistical model for mapping QTL and estimating QTL parameters was discussed and a maximum likelihood procedure based on the model was explained. Using simulated data, the power of QTL detection and the effciency in estimation of QTL parameters with the CIM-based method in diallel cross were evaluated in comparison with a method based on simple interval mapping (SIM). It was shown that two linked QTLs can be resolved more effectively by CIM than SIM. Even in the case of existence of multiple QTLs, unbiased estimates of a position and effects for each QTL were obtained by CIM, while SIM gave much biased estimates in such a case. In conclusion, the CIM-based method is useful in QTL analysis with diallel designs.
Gametic relationship matrix is required for detecting quantitative trait locus (QTL) and implementing marker-assisted selection in outbred populations. The gametic relationship matrix for a QTL flanked by two marker loci can be computed from the marker information, only if haplotype of marker genotype is known for all individuals. When individuals with unknown haplotypes are contained, as in most animal populations, an approximated method is required for constructing the gametic relationship matrix. In this paper, the approximation via Markov chain Monte Carlo method was proposed. The algorithm was illustrated with a small hypothetical population.
We developed a mathematical model of carcinogenesis with the genomic instability hypothesis, a feature characterized by destabilization of the genome is induced in irradiated cells permanently or semipermanently, leading to an increase of cancer risk at cancer age of the exposed individuals. This model also takes into consideration the “ induction of cell death,” which is another important effect of radiation on cells. It is assumed in this model that the effect of radiation exposure on “cell killing” may occur in all stages of carcinogenic process. Using the resulting model, we can explain not only paradoxical reltionship between low mutation rate and high cancer incidence but also the well known empirical evidence from the cohort study on atomic-bomb survivors in Hiroshima-Nagasaki that the excess relative risk of solid cancer incidence for exposed individuals has been almost constant irrespective of the number of years after exposure.