INHERITANCE
All the genetic information that we need
is inherited from our parents. The majority of the genes
are present as two copies, one of which we have received
from each parent. Genetic diseases can be inherited in a
number of ways which are referred to as "Mendelian".
Recessive diseases show up only when both copies of a pair
of genes are abnormal. In dominant conditions, only one
member of the pair needs to be abnormal for the disease to
occur. A few diseases, of which IP is one, are caused by
genes on the X-chromosome and are called "X-linked". This
type of Mendelian inheritance is different because all
females have two X-chromosomes, while males have only one X
(and another, male-determining chromosome called the
Y-chromosome). For most X-linked disorders, females are not
affected since they have two X-chromosomes (one with the
disease gene and one with a normal gene); the effect of the
normal copy of the gene on one X overrides the effect of
the abnormal copy on the other X. Males, however, do not
have this second normal copy; they have only one
X-chromosome, so they have no way to compensate for their
only abnormal X-linked gene and thus they are affected with
the disease. Some rare males can have two X chromosomes
along with their Y--some males with IP have been found who
have this chromosomal anomaly.
IP is a
dominant X-linked
condition. This means that females with only one
copy of the abnormal gene will show the disease, even
though they have a normal gene on their other X-chromosome.
Males who inherit the abnormal gene (and, of course, do not
have a balancing normal copy) do not survive, which
demonstrates that the normal copy of the IP gene is
extremely important. With the identification of the
NEMO gene in IP, we now know that males
lacking a function copy of this gene will not survive
due to liver failure, typically in the first trimester
of pregnancy.
A woman who is affected with IP has one normal
X-chromosome, and one X-chromosome carrying the abnormal
gene. At each
pregnancy she
will give half of her genetic information to each fetus.
Thus, for any pregnancy there is a 50-50 chance that she
will transmit the X-chromosome with the abnormal IP gene,
regardless of the sex of the fetus. On average, half of her
daughters will inherit the normal X-chromosome and be
unaffected, and half will receive the abnormal X and have
IP like their mother. Half of the sons will inherit the
normal X-chromosome and be normal, and the other half will
receive the abnormal X. Since males typically do not
survive without a normal copy of the gene, these
"affected" males will either miscarry or be stillborn. In
summary, half the daughters of an affected IP female will
have IP and half will not, but nearly all the
live-born
sons will be normal. This
50-50 chance for affected females is true for
each
pregnancy, regardless of
whether previous pregnancies have been affected or
not.