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.
Mouse Models for the Analysis of Myopia: Variation in Eye and Lens Size
of Adult Mice
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.
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
See pdf file (2001) 7:253-260.