The Genetics & Molecular Biology Of EDS

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 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.

Autosomal Dominant Inheritance 

Genes are the basic unit of inheritance. They provide the instructions for growth and development of the single cell of a fertilized ovum into the complex structure of a baby. Many continue to provide instructions for the production of proteins needed for bodily functions throughout a person’s lifetime. Genes are strung together like beads on a string and packaged into individual chromosomes. Chromosomes come in pairs; with one coming from an individual’s mother and the other from the father. One pair of chromosomes is called the sex chromosomes, since they determine the sex of the individual; the other 22 pairs of chromosomes are called autosomes.

Since our chromosomes come in pairs, we have two copies of all of our genes. The two copies in a pair of genes may or may not have the same code. A gene that is expressed regardless of the code in the other gene is said to be dominant. An autosomal dominant gene is one carried on one of the 22 pairs of autosomes which means that males and females with the gene are equally likely to pass it on to male or female offspring.

A person who has an autosomal dominant form of EDS (Classical, Hypermobility, Vascular, and Arthrochalasia types) generally has one gene for EDS and one normal gene in one pair of genes. There is a 50 percent chance that the affected parent will contribute the EDS gene and a 50 percent he or she will contribute the normal gene.

There can be variation in the expression of a dominant gene even within the same family. In other words, the gene may cause a profound loss for an individual and only a mild to moderate loss for that individual’s child. Another phenomenon that is seen with some dominant genes is non-penetrance. This means that there is no detectable evidence that an individual with a dominant gene has the gene. When the gene is non-penetrant it appears that the gene has skipped a generation.

Autosomal Recessive Inheritance 

A person with an autosomal recessive EDS (Kyphoscoliosis and Dermatosparaxis types) would have to have two recessive genes for EDS in that particular pair of genes. A person with a normal gene and an EDS gene would not have a EDS, but would be considered a carrier. Generally the EDS gene has been passed down through the carrier’s family for generations. A carrier has no way of knowing that he or she has an EDS gene until having a child with EDS. Then it becomes apparent that the individual and the individual’s spouse each is a carrier. All of us have several recessive genes, each of which could cause significant problems for our children if it happened to get paired up with the same recessive gene from our partner.

For example, if the mother and father are carriers of a gene for EDS, it can be designated with an r. They also have one normal gene which is designated with an R. When they have a child each will pass on one of those genes. If they both pass on the R, the child will have two normal messages, not have EDS and cannot pass the EDS gene to his children. There is 1 chance out of 4 or a 25% chance for the child of two carriers to receive both normal genes. If one parent passes on the R and the other the r, the child will have one normal message, not have EDS, and be a carrier like the parents There are 2 chances out of four, or a 50% chance of the child of two carriers being a carrier also. If both parents pass on an r, the child will have no normal message and will have EDS. There is 1 chance out of 4 or a 25% chance that the child of two carrier parents will receive both EDS genes and have EDS. The chance of carrier parents having a child with EDS is the same with each pregnancy. If they have one child with EDS, it does not mean that their next child will not have a EDS also. The genes are passed on in a random manner and what has already happened in existing offspring has no influence on future offspring.

Regardless of the type of EDS, parents should never feel guilt toward themselves for passing along an EDS gene, this can not be controlled nor predicted in each pregnancy.

Amy William / January 17, 2015 / EDS

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