More than 24,000 children are born with hearing loss in the United States each year. Boys Town National Research Hospital is a national leader in the diagnosis and treatment of children with moderate to profound hearing loss.
Information on Hearing Loss - Genetics and Deafness - Decoding Genes: A Primer on Genetics and
Molecular Biology
The purpose of this primer is to help people understand how geneticists (people who study how traits are inherited) are able to find where genes are located. We will begin with an explanation of some basic genetics.
What is DNA?
The set of genetic instructions is on a very large and complex molecule called DNA. The DNA molecule is like a very long ladder. The backbones of the ladder are repeating sets of a sugar and a phosphate molecule. The rungs of the ladder are made up of a pair of molecules. Each is a chemical base attached to the sugar molecule on the backbone.
The Genetic Message
The genetic alphabet is made up of four bases: Adenine, Thymine, Cytosine and Guanine. They are abbreviated A, T, G, and C. The code for the actual DNA instructions is the order of the bases as they are lined up on one side of the ladder. The lineup of bases on the other side of the ladder is the complementary strand. To keep the backbones of the DNA molecule even, an A base on one side always pairs with T base on the other side, and G always pairs with C.
The complementary bases keep the DNA molecule even and are critically important in allowing the DNA molecule to copy itself. The DNA must copy (replicate) itself before the cell divides so that each new cell can have a complete copy of the message. The first thing the DNA does to replicate itself is to separate down the middle. This splits the paired bases and gives two half-ladders. The exposed bases on each half-ladder creates a pattern for the two new identical copies. Each exposed base now pairs with a new base and new backbones are constructed.
Our English language makes words by stringing letters together. Genetic words are three genetic letters (bases) long. Each genetic word tells the cell to get a molecule called an amino acid. Our English language makes sentences by stringing words together. Genetic sentences are made by stringing different amino acids together; these make protein molecules. There are only 20 amino acids, but by stringing them together in different combinations, a limitless number of different proteins can be made. These proteins are the building blocks and workhorses of the cell. They help the cells carry out the instructions contained in the DNA molecule.
What Are Genes?
Genes contain the instructions that tell cells what to do. Basically each gene is a genetic sentence that produces a different protein.
What Are Chromosomes?
Chromosomes are genetic books. Each one is a very long strand of DNA that contains hundreds of genetic sentences (genes). Like English sentences, genes are meant to be read in a certain direction, and they are arranged in a specific order. Unlike the organization of sentences in a book, the arrangement of genes on the chromosomes do not have to make a sensible story. For example, a gene that produces a protein that influences hair color may be next to a gene that helps the cell produce energy. The place where a given gene lies along the length of a chromosome is its genetic locus. Just as books come in different sizes and thickness, chromosomes can also have different lengths and shapes.
Pairs of Genes, Pairs of Chromosomes
Chromosomes (and genes) come in pairs. The two members of each pair of chromosomes are called homologs. One homolog came from your father and the other came from your mother. Humans have 23 pairs of chromosomes. Twenty-two of these pairs are numbered for identification. They look the same in males and females and are called autosomes. The 23rd pair is called the sex chromosomes because they determine the sex of the child. Females have two identical sex chromosomes call X chromosomes. Males have and X and a Y chromosome. The presence of the Y chromosome determines maleness.
Different traits are determined by gene pairs. A person with similar genes is homozygous at that locus. One with different genes is heterozygous for that locus. The ways in which the genes are homozygous or heterozygous determine the different types of inheritance. The three main types of inheritance are autosomal dominant, autosomal recessive, and sex-linked recessive.
Reading the Genetic Code
Until very recently, it was next to impossible to decode the genetic messages. The human DNA message is about 3 billion bases long. There are approximately 100,000 genes, so each gene has an average of 30,000 bases coding for 10,000 amino acids each.
Restriction Enzymes
In the early 1970's, scientists discovered that bacteria had enzymes that would attack foreign DNA and cut the DNA up into little pieces. What was interesting was that these enzymes were restricted to a specific sequence of the genetic alphabet to make the cut. This is why they are named restriction enzymes (RE). There are over 200 restriction enzymes known and many cut the DNA in different places.
Genetic Probes
A genetic probe is a piece of DNA that matches the message you are trying to find. This probe also may be labeled with a radioactive chemical.
Molecular Genetics
The technique for finding genes goes something like this. First you cut the DNA with a restriction enzyme. All the pieces of DNA after one of these cuts are called restriction fragments. Next you separate the all the cut DNA by the size of the resulting pieces. If you put the DNA in a gel (like unflavored Jello) and pass an electric current through the gel, the DNA will migrate in the direction of the current. The smaller pieces will migrate further than larger pieces. Next you transfer the DNA to a piece of filter paper, like a coffee filter [it is easier to work with paper than with Jello!!]. Next you use the radioactive labeled probe to find the restriction fragment(s) that match the probe. The probe will attach to the restriction fragment(s) it matches. Finally, you can see where the probe attached to the DNA on the paper by exposing it to a sheet of unexposed X-ray film. This is autoradiography. You can estimate the size of DNA fragments by how far they have migrated. Small pieces move farther than bigger pieces. All the DNA fragments revealed by this technique are called RFLPs, which stand for Restriction Fragment Length Polymorphism.
Family Studies
Frequently we do not have a probe that is complementary to the DNA of interest. Instead we can use a piece of anonymous DNA - this is one where the message is known and that message doesn't mean anything. If we take DNA from family members with a known genetic condition, we can apply these techniques to look at the RFLPs in that family. If one RFLP is consistently found in all family members with the same condition, we have good evidence that RFLP either contains or is very close to the gene causing the condition.
Example of How a Restriction Enzyme and Probe Work
Let us assume the first sentence in the paragraph under Restriction Enzymes, is a length of DNA from a certain person. We have an enzyme that cuts between the 'h' and the 'e' in the sequence 'the'. Let's name this restriction enzyme TH1. After cutting, we have three fragments ranging in size from 4 to 86 characters. If we have a probe that highlights (with double underlines and bold letters) those sentences that contain the letters 'DNA', we would end up with the following:
[original sentence]
In the early 1970's, scientists discovered that bacteria had enzymes that would attack foreign DNA and cut the DNA up into little pieces.
After cutting, sorting and probing, the sentence fragments look like this.
length |
message |
------------------ |
---------------------------------------------------------------------- |
4 |
In the |
22 |
e DNA up into little pieces. |
86 |
e early 1970's, scientists discovered that bacteria |
had enzymes thatwould attack foreign DNA and cut th |
|
------------------ |
---------------------------------------------------------------------- |
We can say this person has RFLPs of 22 and 86 bases highlighted when we cut with the TH1 enzyme and probe with "DNA".
If the other "allele" in that pair was:
In the early 1970's, there were reports of bacterial enzymes that would attack foreign DNA, cutting them into little pieces.
After cutting, sorting and probing, the sentence fragments look like this.
4 |
In th |
13 |
e early 1970's, th |
18 |
em into little pieces. |
64 |
ere were reports of bacterial enzymes that |
| would attack foreign DNA, cutting th |
This person's allele has four fragments that are different lengths than the original sentence. When probed with "DNA", only the RFLP of 64 bases is highlighted.
Thus, RFLPs can distinguish differences between alleles in DNA messages. If one of the alleles contains a message responsible for a genetic condition such as Usher syndrome, this method can be used to detect it.
Definitions
Chemical atoms:
a basic element that cannot be further divided. For example, carbon (C), Hydrogen (H) and Oxygen (O) are atoms.
Molecule:
Combinations of chemical atoms. For example, a water molecule is made up of one Oxygen and two Hydrogen atoms in the formula H2O.
Amino acid:
A special molecule that is the building block of proteins.
Protein:
A special molecule made up of different combinations of amino acids. Proteins do many things. Some of these include providing structure to the cell (building blocks), assisting biochemical reactions (enzymes) and as antibodies, they identify foreign objects for removal. Proteins can also combine with non-proteins to do other things. These include glyco-proteins, lipo-proteins, and nucleo-proteins.
RFLP (pronounced "rif-lip"):
the initials stand for Restriction Fragment Length Polymorphism. These are different (polymorphic) pieces of DNA (length) that are produced by cutting the DNA with restriction enzymes and probing them with labeled DNA.
Date Originally Created: Spring of 1990
The information presented here first appeared in publications of the Boys Town National Research Register for Hereditary Hearing Loss, the National Institute on Deafness and Other Communication Disorders (NIDCD), Hereditary Hearing Impairment Resource Registry (HHIRR), or the Boys Town Research Registry for Hereditary Hearing Loss.
The Boys Town Research Registry for Hereditary Hearing Loss
The Boys Town Research Registry for Hereditary Hearing Loss (Registry) is designed to foster a partnership between families, clinicians and researchers in the area of hereditary hearing loss/deafness through three primary functions. First, the Registry disseminates information to professionals and families about clinical and research issues related to hereditary deafness/hearing loss. Second, the Registry collects information from individuals interested in supporting and participating in research projects. This information is used to support the third function of the Registry - matching families with collaborating research projects.
For more information, contact us at:
Research Registry for Hereditary Hearing Loss
555 N. 30th Street Omaha, NE 68131
800 320-1171 (V/TDD)
402 498-6331 (FAX)