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.WHY IS IT DIFFICULT TO FIND A GENE?
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.
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.