Fragile X Syndrome : Human Cells 101, Inheritance

by National Institute of Health

(Page 2 of 9)

Human Cells 101

More than 100 trillion cells make up the human body. Most of these cells contain all the genes and other information needed to "build" a human being. Much of this genetic information is found in the nucleus of the cell, a "control center" that keeps all the material together in one place.

The nucleus stores its genetic material in packages called chromosomes. Most people have 46 chromosomes in each cell - 23 from their mother and 23 from their father. After fertilization, the two sets of chromosomes match up to form 23 pairs. The chromosomes in the 23rd pair are called the sex chromosomes, X and Y; they determine a person's sex. Males usually have one Y chromosome and one X chromosome; females usually have two X chromosomes.

Each chromosome is made up of genes. Genes contain the information used by other parts of the cell to make proteins, the body's building blocks. Proteins make up the structure of your organs and tissues; they are also needed for your body's chemical functions. Each protein performs a specific job in different types of cells, and the information for making at least one protein is contained in a single gene.

Genes are made up of various lengths of DNA, which contains four chemicals: adenine (A), guanine (G), cytosine (C), and thymine (T). These chemicals line up like beads on a necklace to form strands of code. They also pair up with each other to form the double strands that are characteristic of DNA.

The gene's chemical code for a protein has two parts: the introduction area (promoter), and the instructions for creating the protein. The instructions for making the protein are inside the cell's nucleus, but the parts that actually make the protein are outside the nucleus. To send the instructions to the protein-producing areas of the cell, the gene "reads" the chemical code and rewrites it into a new form (called messenger RNA). The new form is then sent out of the cell's nucleus to make proteins. But, if either the original code or the new form of the code is incorrect or has missing parts, the cell can't make the correct protein. Without the protein, the body may not develop or function normally.

This is what happens in Fragile X. The FMR1 gene contains too many repeats of one specific sequence, CGG, which is an important part of the promoter region for making FMRP.

The number of CGG repeats affects how the code is read and rewritten into its new form. So when the new form of the code gets to the protein-making areas of the cell, the cell has trouble using it to make FMRP, the protein that is abnormal, missing, or in low amounts in people with Fragile X. The cell either can't use the code, and so makes no FMRP, or tries to use the code and makes abnormal or unusable FMRP.

How many people are effected by Fragile X syndrome?

Currently, researchers don't know exactly how many people have either the full mutation or the premutation form of the FMR1 gene. Even though researchers can estimate the number of people affected by Fragile X, these estimates can be very different.

A summary of existing research conducted by the Centers for Disease Control and Prevention in 2001 estimated that approximately one in 3,500 to 8,900 males is affected by the full mutation of the FMR1 gene, and that one in 1,000 males has the premutation form of the FMR1 gene. This study also estimated that one in 250 to 500 females in the general population has the premutation. Another study estimated that one in 4,000 females is affected by the full mutation.

Although these estimates are useful in trying to understand the impact of Fragile X on various communities, keep in mind that these numbers are only the best estimates based on the available information. Many factors can affect the completeness and/or accuracy of the available information, which means that the number of people affected by Fragile X could actually be different. The important thing to remember is that, when you consider the individuals affected by full mutation and premutation forms of the FMR1 gene, their families, and their communities, this condition impacts hundreds of thousands of people.

How is Fragile X syndrome inherited?

The gene for Fragile X is carried on the X chromosome. Because both males (XY) and females (XX) have at least one X chromosome, both can pass on the mutated gene to their children.

A father with the altered gene for Fragile X on his X chromosome will only pass that gene on to his daughters. He passes a Y chromosome on to his sons, which doesn't transmit the condition. Therefore, if the father has the altered gene on his X chromosome, but the mother's X chromosomes are normal, all of the couple's daughters would have the altered gene for Fragile X, while none of their sons would have the mutated gene.

Current research indicates that a father can pass on the premutation form of the FMR1 gene only to his daughters. In other words, if a daughter inherits the mutated FMR1 gene from her father, she will get only the premutation from him, not the full mutation. Even if the father himself has a full mutation, it appears that sperm can carry only the premutation. Scientists don't understand how or why fathers can only pass on the milder form of Fragile X to their daughters. This remains an area of focused research.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.