By Laura Freeman
Women are different. Unlike men, whose DNA is the same in every cell of their bodies, women are mosaics. Assuming the law of averages, roughly half of the cells in a woman’s body are likely to be identical. The other half would tend to display a different active X chromosome.
“Very early in the development of a female embryo, most of the genes in one of the two X chromosomes are switched off,” said Bruce Korf, MD, Associate Dean for Genetic Medicine at UAB. “The process of selecting which X chromosome to inactivate seems to be random in each cell. On average, the probability would be that female babies would be born displaying the X chromosome from one parent in about half their cells and from the other parent in the rest.
“Usually you aren’t able to see the difference by looking at a woman except in the case of a rare pigment disorder that develops from a gene on the X chromosome. While we don’t want to overstate the protective effects, it is true that in a disease like Duchenne Muscular Dystrophy that develops from a gene on the X chromosome, women have an advantage. Since men only have one copy of X, if they have a defective gene for a disorder coded on that chromosome, they will develop the disease. With genes from two copies of the chromosome, women usually have at least one good gene to protect them. It would require the same mutation on a gene from both her father and her mother for a woman to have the full blown disease. She would be more likely to be only a carrier. It would be very long odds for her to develop the disorder, since few males born with the Duchenne gene live long enough to pass it on.”
There is a huge difference in the size of the X and Y chromosomes and the number of genes each carries. The X chromosome has around a thousand genes, some of which are yet to be fully understood. The Y chromosome has become smaller over time and now only has around 100 genes, some 80 of which are involved in the development of the male reproductive system.
“The Y chromosome is highly specialized,” Korf said. “Perhaps the biggest health difference in men comes from its role as the first domino. It starts the development of male organs that produce testosterone in quantities capable of influencing the traits we associate with maleness like body hair and muscle strength.”
Testosterone also affects the brain. Even the structure of the brain, arm muscles and pelvic bones differs between men and women to equip them to produce and protect the next generation. Unfortunately, the Y chromosome doesn’t give male bodies the same protection estrogen gives women against heart disease and other risks.
When some people hear the term mosaic, they think of an archeological dig from the Roman era with tiny stones creating decorative images in the floors found in Pompeii or Roman Britan.
When medical people hear the term, they tend to think of problems faced by people who have a genetic anomaly that makes them neither XX nor XY, but XXY or XYY or an even more complex combination of X and Y that may be associated with health and even behavior problems.
But in women, being a mosaic isn’t a disorder. Women’s bodies are capable of inactivating one of their two X chromosomes within each cell. Without this ability, XX women might not survive. In rare cases, women are born with only one copy of the X chromosome, which results in a disorder known as Turner syndrome that is associated with short stature, ovarian failure and heart issues. The XX mosaic capability seems to be an adaptive ability that evolved to help protect women and the next generation. It will take more research to understand its full effects.
Women can’t give the men in their families the protection of the mosaic effect. However, there are other ways they can help to protect their sons, nephews and grandsons.
“When a man gives a family history to your doctor, don’t forget to include the women in your family. Women who have ovarian, uterine or breast cancer tend to have male relatives who have prostate and other reproductive system cancers. The same is true of other conditions. People can inherit the health they start with from both sides of their family,” Korf said.
When family history isn’t known, patients may want to consider getting a clinical evaluation. Some home DNA kits cover a few genetic disorders. The All of Us project and the Alabama Genomic Health Initiative are two research programs open to local volunteers. They are looking for specific gene-linked disorders and will alert those who wish to know if they are at high risk for a treatable disorder. A 30-year-old who was unaware of being at high risk for colon cancer on both sides of the family was alerted in time to have numerous polyps removed that could have been lethal before the usual screening age.
“However, if you are concerned about knowing what your genetic risks may be, you may want to consider a full clinical evaluation and counseling, which is available at UAB. The risks you know are easier to avoid,” Korf said.