WHAT IS A GENE?
Genes are the chemical messengers of
heredity. They are tiny, invisible packets of biochemical
information (DNA) that direct how our bodies develop and
function. They regulate every life process. We all inherit
tens of thousands of genes from our parents, arranged on 46
chromosomes. Genes turn on and off to control our growth,
body chemistry and even the color of our hair and eyes.
Most genes work correctly, but some do not. Sometimes they
change (mutate) and then they work poorly or not at all.
Mutations can be caused by unexplained accidents within our
cells.
HOW ARE GENETICS INVOLVED IN INCONTINENTIA
PIGMENTI?
Each of us has 46 chromosomes in a set of
23 pairs in every cell of our bodies except eggs and sperm.
These chromosomes are different sizes and shapes and
contain thousands of genes that act as a "blueprint" for
how each of us develops. Two chromosomes determine our sex:
the X and Y chromosomes. Females get one X chromosome from
each parent (XX); males receive an X chromosome from their
mothers and a Y chromosome from their fathers (XY).
Since females have two copies of the X chromosome and need
only one working copy for its genetic information, they
"turn off" the extra X in a process called " X
inactivation". Normal females turn off one X chromosome in
each of their cells (usually about half the cells turn off
the mother's X, and half the father's X) in a random
pattern that leaves them with one functional X in most
cells. Because males lack a back-up copy of the X
chromosome that could compensate for a defective one,
mutations on the X chromosome are often devastating in
boys.
The first hypothesis to help narrow the search was based on
the fact that IP is seen only in girls. This made it likely
that IP is caused by an X-linked dominant mutation that
would be lethal in males. Exclusion mapping studies
narrowed the probable location on the X chromosome to a
region known as Xq28. In the case of the IP gene, the NEMO
mutation affects the fetus in such important ways that boys
die either before or shortly after birth and never have the
chance to develop IP.
WHY IS IT DIFFICULT TO DISCOVER GENE
MUTATIONS?
The 23 human chromosome pairs carry some
100,000 genes. Finding one specific gene on a chromosome -
or worse, the defect lurking in one of its billions of
nucleic acids - without some sort of clue to its location
is like looking for the proverbial needle in a haystack. If
one took a magnet to that haystack one might attract old
nails, screws, and other metal scraps, but would eventually
be able to pull out that needle.
"Linkages" or genetic "markers" are segments of DNA that
are inherited with the defective gene from one generation
to the next. Using special enzymes that cut DNA at known
spots along its length, geneticists can subdivide the
material, always searching for a smaller piece that still
contains the defective gene. It is much easier to map the
location of a defective gene if one can compare DNA from
many members of one family, both affected and unaffected,
since these family members will have many DNA sequences in
common, and thus provide genetic
markers.