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Biomedical subjects

Y-M Zhang

Publications and source records attributed to Y-M Zhang.

6 recordsLinked to original sources

An EM algorithm for mapping quantitative resistance loci.

Many disease resistance traits in plants have a polygenic background and the disease phenotypes are modified by environmental factors. As a consequence, the phenotypic values usually show a quantitative variation. The phenotypes of such disease traits, however, are often measured in discrete but ordered categories. These traits are called ordinal traits. In terms of disease resistance, they are called quantitative resistance traits, as opposed to qualitative resistance traits, and are controlled by the quantitative resistance loci (QRL). Classical quantitative trait locus mapping methods are not optimal for ordinal trait analysis because the assumption of normal distribution is violated. Methods for mapping binary trait loci are not suitable either because there are more than two categories in ordinal traits. We developed a maximum likelihood method to map these QRL. The method is implemented via a multicycle expectation-conditional-maximization (ECM) algorithm under the threshold model, where we can estimate both the QRL effects and the thresholds that link the disease liability and the categorical phenotype. The method is verified in simulated data under various combinations of the parameters. An SAS program is available to implement the multicycle ECM algorithm. The program can be downloaded from our website at www.statgen.ucr.edu.

Algorithms↗

A quantitative genetics model for viability selection.

Viability selection will change gene frequencies of loci controlling fitness. Consequently, the frequencies of marker loci linked to the viability loci will also change. In genetic mapping, the change of marker allelic frequencies is reflected by the departure from Mendelian segregation ratio. The non-Mendelian segregation of markers has been used to map viability loci along the genome. However, current methods have not been able to detect the amount of selection (s) and the degree of dominance (h) simultaneously. We developed a method to detect both s and h using an F2 mating design under the classical fitness model. We also developed a quantitative genetics model for viability selection by proposing a continuous liability controlling the viability of individuals. With the liability model, mapping viability loci has been formulated as mapping quantitative trait loci. As a result, nongenetic systematic environmental effects can be easily incorporated into the model and subsequently separated from the genetic effects of the viability loci. The quantitative genetic model has been verified with a series of Monte Carlo simulation experiments.

Algorithms↗

A penalized maximum likelihood method for estimating epistatic effects of QTL.

Although epistasis is an important phenomenon in the genetics and evolution of complex traits, epistatic effects are hard to estimate. The main problem is due to the overparameterized epistatic genetic models. An epistatic genetic model should include potential pair-wise interaction effects of all loci. However, the model is saturated quickly as the number of loci increases. Therefore, a variable selection technique is usually considered to exclude those interactions with negligible effects. With such techniques, we may run a high risk of missing some important interaction effects by not fully exploring the extremely large parameter space of models. We develop a penalized maximum likelihood method. The method developed here adopts a penalty that depends on the values of the parameters. The penalized likelihood method allows spurious QTL effects to be shrunk towards zero, while QTL with large effects are estimated with virtually no shrinkage. A simulation study shows that the new method can handle a model with a number of effects 15 times larger than the sample size. Simulation studies also show that results of the penalized likelihood method are comparable to the Bayesian shrinkage analysis, but the computational speed of the penalized method is orders of magnitude faster.

Bayes Theorem↗

The DNA excision repair system of the highly radioresistant bacterium Deinococcus radiodurans is facilitated by the pentose phosphate pathway.

Deinococcus radiodurans is highly resistant to radiation and mutagenic chemicals. Mutants defective in the putative glucose-6-phosphate dehydrogenase gene (zwf-) and the aldolase gene (fda-) were generated by homologous recombination. These mutants were used to test the cells' resistance to agents that cause dimer formation and DNA strand breaks. The zwf - mutants were more sensitive to agents that induce DNA excision repair, such as UV irradiation and H2O2, but were as resistant to DNA strand break-causing agents such as methylmethanesulphonic acid (MMS) and mitomycin C (MMC) as the wild-type cells. Analysis of the cytoplasmic fraction of zwf- cells showed that the concentrations of inosine monophosphate (IMP) and uridine monophosphate (UMP) were only 30% of those found in the wild-type cells. The fda- mutants were slightly more resistant to UV light and H2O2. Results suggested that the deinococcal pentose phosphate pathway augmented the DNA excision repair system by providing cells with adequate metabolites for the DNA mismatch repair.

DNA Damage↗

Therapeutic penetrating keratoplasty in severe fungal keratitis using cryopreserved donor corneas.

AIMS: To investigate whether cryopreserved donor cornea could be used for therapeutic penetrating keratoplasty (PKP) to eradicate the infection, obviate complications, and preserve anatomical integrity in severe fungal keratitis. METHODS: In this retrospective, consecutive case series, 45 eyes of 45 patients with severe fungal keratitis, which exhibited anterior chamber collapse, corneal perforation, and/or large suppurative corneal infiltrate, received therapeutic PKP after removal of the infected corneal tissue, irrigation of the anterior chamber by 0.2% fluconazole solution, iris dissection of fibrinoid membrane, and iridectomy and therapeutic PKP using corneas cryopreserved at -20 degrees C. RESULTS: Among 45 eyes, 39 eyes (86.7%) were successfully eradicated the fungal infection without recurrence and maintained their anatomical integrity without any complication. Four of 45 eyes (8.9%) showed postoperative rise of intraocular pressure, of which three were controlled with subsequent antiglaucoma surgeries, whereas one eye needed additional antiglaucoma medications. Two of 45 eyes (4.4%) were enucleated because of uncontrollable fungal infection and secondary retinal detachment, respectively. 23 eyes received subsequent optical PKP and, among them, 21 maintained clear corneal grafts and two suffered from graft failure due to allograft rejections. CONCLUSION: Cryopreserved donor corneas are effective substitutes in therapeutic PKP to control severe fungal corneal infection and preserve the global integrity, and may offer additional advantages over conventional PKP in reducing allograft rejection, eradicating fungal infection during the postoperative period, and improving the success of optical PKP for visual rehabilitation.

Administration, Oral↗

Normalized fifth-order spherical aberration coefficients derived from a Gaussian trajectory on rotationally symmetrical magnetic lenses.

This paper reports normalized fifth-order spherical aberration coefficients C(5s)/R derived from Gaussian trajectory for rotationally symmetrical magnetic lenses, where S/D (the polepiece gap-width/bore-diameter ratio) is in the range 0.20-2.00, and k(2) (the lens-intensity parameter) is 0.10-100. It is noted that the normalized fifth-order spherical-aberration coefficient C(5s)/R changes its sign within the given parameter ranges.

Journal Article↗