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Quantitative Neurogenetics & QTL Mapping

Genetics of Myopia

Control of Neuron Number and Stereology

Growth Cones and Dying Axons

Retina Development and Visual System Mutants

Grant Application

U.S. Patent


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 Genetics of Eye Size and Myopia

  • Eye1 and Eye2: Quantitative trait loci that modulate eye size, lens weight, and retinal area

    This is a preprint of a paper that explores the genetic basis of variation in the growth of the mouse eye. The print edition was published in Investigative Ophthalmology and Visual Science, April, 1999.

    The Eye1 locus. Linkage between variation in eye weight and proximal Chr 5. The x-axis represents the entire genetic length of Chr 5 from the proximal end (left) near marker D5Mit346 to the distal end of the chromosome at approximately 60 cM (far right). The y-axis represents the strength of linkage assessed using the likelihood ratio statistic (LRS) computed at 1 cM intervals using an interval mapping procedure without any adjustment for secondary QTLs using data for the 26 BXD strains. The peak LRS of 24.9 is ~1 cM distal to D5Mit346. The horizontal white bar extending from D5Mit346 to just beyond D5Mit1 indicates the 2-LOD confidence interval of the position of the Eye1 QTL. The inset histogram in the upper right shows the distribution of peak LRS scores for a set of 20,000 permutations of eye weight mapped across the entire genome. Only 116 of the permutations (0.58%) attained an LRS as high or higher than that of Eye1. In contrast the LRS for Eye2 is approximately 10, and the genome-wide probability of achieving this level by chance is shown to be about 0.4. Eye2 was subsequently confirmed by analysis of F2 progeny and the cumulative data for this locus have a genome-wide p of < 0.05. Three criterion levels (p = 0.5, 0.05, and 0.005) are shown both on the histogram and on the LRS plot.

  • Mouse Models for the Analysis of Myopia: Variation in Eye and Lens Size of Adult Mice

    Our aim is to develop mice as a model species for research on myopia. Myopia is casued by a comparatively modest overgrowth of the back part of the eye. We would like to know what genes and molecular mechanisms contribute to eye growth in general, and to the overgrowth of myopia in particular. This paper provide a lot of essential data on the size and growth of the normal mouse eye, lens, and retina. We've included a great deal of information on correlations among several important size parameters. For example, one might expect lens size and eye size to be tightly related in mice, but they are not. The print edition of this paper was published in a special myopia issue of Optometry and Vision Science (1999) 76:408 418.

  • Modulation of Retinal Cell Populations and Eye Size in Retinoic Acid Receptor knockout Mice

    The retinoic acid receptors are expressed from early stages of development in the diverse tissues that make up the vertebrate eye. Their loss has subtle effects on eye development. We adapted sensitive quantitative trait locus (QTL) mapping methods to assess consequences of inactivating alleles of the alpha and beta receptors, Rara and Rarb, on eye and retinal development. Rara is of particular interest because this gene is a candidate for Nnc1, a QTL that controls retinal ganglion cell proliferation. See pdf file (2001) 7:253-260.


    Three-Dimensional Counting
    An Accurate and Direct Method to Estimate Numbers of Cells in Sectioned Material.
    A field of cells and a superimposed counting frame imaged using video-enhanced differential interference contrast (DIC) optics on a television monitor.

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