Elucidation of the genetic basis of a major X-linked QTL influencing muring growth

Body size varies substantially among individual humans and among
individuals of other mammalian species. Part of this variation is
genetic, and causes relatives to resemble each other more than
unrelated individuals. In previous work we had found evidence that a
gene located on one of the mouse sex chromosomes (chromosome X) is
responsible for a large difference in body size between two lines of
laboratory mice. The lines had been bred by artificial selection to be
large and small. The aim of the project was to identify which gene on
the X chromosome causes this difference and to determine how the
protein product of this gene acts to cause its body size effect. We
took advantage of the availability of the complete genome sequence of
the mouse and a large mouse breeding experiment to map the gene to a
small region of the X chromosome. There were only four genes in this
region that were plausible candidates for the body size effect, and
one of them, Gpc3, was a particularly strong candidate because it causes
gigantism when mutated in both humans and mice. By studying the
product of this gene we were able to demonstrate that variation in
parts of the Gpc3 gene that regulate the amount of its product causes the
difference in body size. We found that the differences in body size is
extremely specific, and other traits are largely unaffected by the difference
in the gene. In parallel, by similar means, we also identified the
gene causing a difference in body size in a different set of mouse
lines.