FMR1 Gene

What Is a Gene?

A gene is a unit of heredity that is passed down from parent to child. Genes are located on chromosomes that are in all of our cells, including the sperm and egg that make a baby.

What Is a Gene Made Of?

Genes are made of molecules or chemicals called DNA. The pattern of DNA will determine if the gene is working properly. The DNA has to be in a certain pattern or order, like the numbers in a phone number.

How Does a Gene Work?

A gene has different parts that work together like a factory or machine. It has a “promoter” that turns the gene on, like a light switch. It has sections that are just “filler” and act as place holders, called “introns.” The sections that are used to make a protein or do a job are called “exons.”

What Do Genes Do?

The job of a gene is to either make a protein, the building blocks of all the structures in the body, or to regulate other proteins in the body.

How Does a Gene Make Proteins?

The DNA in the gene is a code that is “transcribed” or “talks” to another kind of molecule called RNA. This is like one side of Velcro sticking to another that it matches up to. The RNA then “translates” the DNA to put together the protein.

Now that you understand what genes are, let’s discuss the Fragile X gene…

The Fragile X (FMR1) Gene

Why Is It Called the FMR1 Gene?

Genes are named when they are discovered. Often the name isn’t exactly the same as the condition, in case it is later discovered that there is more than one gene involved in the condition. The gene that causes Fragile X is called the “FMR1 gene,” which stands for Fragile X mental retardation gene. Though the term “mental retardation” has given way in recent years to the more generally accepted term of “intellectual disabilities,” the scientific name of the gene can’t change with the times.

Ideogram of X chromosome

Where Is the FMR1 Gene Located?

The FMR1 gene is located on the X chromosome. We all have 46 chromosomes in all of our cells, 44 of which are numbered 1-22 in pairs. Then females have two X chromosomes and males have one X and one Y chromosome. Each chromosome has two arms, one called the “p” arm (the short arm) and one called the “q” arm (the long arm).

There are many genes on each chromosome, like houses on a street. Each gene is given an address, depending on where it lies on the chromosome. The address of the FMR1 gene is Xq27.3

Does Everyone Have an FMR1 Gene?

Yes, everyone has an FMR1 gene. When someone states, “I have the gene for Fragile X,” they really mean they have a gene mutation for Fragile X. Some Fragile X genes are normal and some are not.

What Does the FMR1 Gene Do?

The FMR1 gene makes a very important protein called FMRP (Fragile X mental retardation protein). Though this protein is found in all our cells, it is most abundant in the nerve cells, and particularly in a part of the nerve cell that “talks” to other nerve cells called “dendrites.”

What Is an FMR1 Gene Mutation?

A mutation is any change in a gene. Some mutations don’t cause any problems and we don’t know about them (unless found in the laboratory). Mutations in the FMR1 gene involve an abnormal expansion of the DNA in the “promoter” area of the gene. Often a mutation causes decreased or absent protein production. In individuals with a “full mutation,” their FMR1 gene is shut down and they don’t make enough or any FMRP.

Are There Different Kinds of FMR1 Mutations?

Yes. An individual can have a normal FMR1 gene, a “premutation” or a “full mutation.” There is also another category called an “intermediate allele,” which is not a true mutation, but an expansion somewhere between the “normal” FMR1 gene and the premutation.

What Is the Difference Between These Mutations?

FMR1 Gene Categories

The mutation of the FMR1 gene involves a repeating pattern of DNA called a “CGG repeat.” DNA is made of molecules that are abbreviated A, C, G and T. A CGG repeat in the FMR1 gene is a pattern of DNA that may repeats itself anywhere from 30 to 1000 times. In the FMR1 gene there is an area of the promoter that is rich in these CGG repeats and is measured when Fragile X testing is performed.

In this area, there is normally about 30 repeats of CGG. In individuals with the premutation, there are from 55-200 of these repeats. Persons with the full mutation have more than 200 of the CGG repeats. When there is more than 200 CGG repeats, the gene is turned off by a process called Methylation.

Methylation happens to other genes too, when they are supposed to be turned off (as in the genes we don’t use, like those that make a tail grow!). In Fragile X the methylation turns off the FMR1 gene, so no FMRP is produced. This is what causes Fragile X Syndrome.