Genetics 101

• What are genes?
• How do we inherit our genes?
• What is a mutation?
• What kind of problems can mutations cause?
• What is Genetic Testing?
• When should I consider having a genetic test?
• Are there different types of genetic tests?
• What should I expect from a genetic test?
• What do the results mean?
• What are the risks and limitations of genetic testing?
   

What are genes?

 
Genes are like the instructions that tell our bodies how to develop and function normally.  Genes are comprised of a long row of DNA molecules which are like the letters that make up the words or instructions. The alphabet of DNA has only 4 letters, A, T, G and C.  Each gene has a function.  Perhaps it makes a product, like an enzyme that helps us to digest food, or a molecule that helps our nerves communicate with each other.  The specific combination of the letters in our genes controls how our genes function.  When an instruction is misspelled, the gene might not function normally, and this is when genetic disease occurs.

A chromosome is a string of many genes all lined up one after another.  Human beings have 46 chromosomes, each covered with thousands of genes.   Each chromosome contains thousands of genes, each of which is several thousand base-pairs long. A gene is any section along the DNA that has instructions encoded that allow a cell to produce a specific product, usually a protein that serves one particular function in the body. There are between 20,000 and 30,000 genes, and every single gene is made up of thousands, even hundreds of thousands, of DNA molecules.
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How do we inherit our genes?

 
Scientists say that a gene is a basic unit of heredity in a living organism, meaning that every living creature or plant or bacteria is made up of genes.  Our genes are given to us by our parents.  When the egg and sperm combine to make a new human being, each provides 23 chromosomes, providing us with a total of 46 chromosomes. Of the 46 chromosomes, 44 are known as “autosomes” and are present in both men and women. . Autosomes typically contain two copies of each gene, one contributed from each parent.  Some of us might resemble one parent more than the other, but we still inherit about half of our genetic information from each one. The remaining two chromosomes are called sex chromosomes, which are designated X and Y. Women inherit two X chromosomes, one from each parent, and , men inherit one X chromosome from their mother and one Y chromosome from their father. Whilst women have two copies of each gene on the X chromosome, men only have genes they inherit from their mother on the X chromosome and only genes they inherit from their father on the Y chromosome.
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What is a mutation?

 
When there is a change in the sequence of DNA letters that make-up a gene, this can change the instructions communicated by that gene and interfere with its ability to do its job, or make its protein.  This misspelling is considered a mutation. Just like changing a letter in a word can change the word’s meaning, a mutation can change the instruction contained in the gene. Mutations can range in size from a single DNA ”letter”, which may have little effect, to a deletion of a large piece of a chromosome causing the gene not to function at all, and make none of its required product.
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What kind of problems can mutations cause?

 
Some mutations result in proteins that do not function normally, and may end up causing disease. There are several ways that a gene mutation can change the way a protein functions, including:
 

• Altered function - Some mutations result in a protein that cannot carry out its normal function in the cell, or cannot carry out that function very well. One example of this type of mutation is sickle cell disease. In this disorder, an altered protein in red blood cells alters the shape of the red blood cell, which causes the cell to become stuck in blood vessels. This prevents cells from carrying sufficient oxygen to the rest of the body.
• Lack of protein - Some mutations prevent the protein from being made altogether. One example of this type of mutation is hemophilia. In this condition, a mutation results in the absence of a protein that allows blood to clot. The result is uncontrolled bleeding in response to injury.
• Change in how much protein is made - Some mutations cause too much or too little of a normal protein to be made. Although the protein itself functions properly, it is not present in quantities that are appropriate. One example of this is in the development of some cancers. In this case, a protein that prevents additional mutations from building up can become turned off. Without this protein, the cell accumulates mutations and becomes cancerous.

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What is Genetic Testing?

 
The human genome is believed to contain around 20,000 - 30,000 genes. Genetic testing identifies changes in chromosomes, genes, or proteins and can confirm or rule out a diagnosis, suggest an increased risk to develop a particular disorder, or determine that an individual is a carrier for a particular condition and might pass that gene on to their children.

A pediatrician or a general physician may refer a child to a clinical geneticist because of a suspicion that a child has a genetic disorder based on facial features,or other physical characteristics observed in the child.  
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When should I consider having a genetic test?

 
Genetic tests are used for a variety of reasons, including:
 

• Carrier screening (identifying if a person can pass on a mutation to their offspring);
• Pre-implantation genetic diagnosis (testing a fertilized egg before it is implanted into a woman’s womb);
• Pre-natal diagnostic testing (testing a developing a fetus while it is in the womb);
• New-born screening (testing a child immidiately after birth);
• Pre-symptomatic testing for predicting adult-onset disorders;
• Pre-symptomatic testing for estimating the risk of developing adult-onset cancers and Alzheimer disease; and
• Diagnostic testing to diagnose or rule out a specific genetic condition. Genetic testing is often used to confirm a diagnosis when a particular condition is suspected based on physical features and symptoms. Diagnostic testing is not available for all genes or all genetic conditions.

 
There are three general categories of genetic tests:

• Chromosomal tests (whole chromosomes or very long lengths of DNA are tested)
• Gene tests (individual genes or relatively short lengths of DNA or RNA are tested)
• Biochemical tests (protein levels or enzyme activities are tested)

What is a chromosomal test?

Chromosomes are the large DNA-containing structures in the nucleus of a cell. Chromosomel tests look at features of a person's chromosomes, including their structure, number and arrangement. These tests look for changes, such as pieces of a chromosome being deleted, expanded, or being switched to a different chromosomal location.
 

Types of chromosomal tests include:

• Karyotyping - Karyotyping involves obtaining and culturing cells, followed by chromosome staining to allow visualization under a microscope. Karyotyping provides a picture of all of a person's chromosomes from the largest to the smallest and can identify changes in chromosome number and large changes in DNA structure (e.g., Down syndrome caused by the presence of an extra copy of chromosome 21).
• FISH (fluorescence in situ hybridization) - This test identifies certain regions on chromosomes using fluorescent DNA probes. FISH analysis can find small pieces of chromosomes that are missing or have extra copies. These small changes can be missed by the overall karyotype test.
• CGH (Comparative genomic hybridization) or CMA (Chromosomal Microarray Analysis) is a molecular-cytogenetic method for the analysis of copy number changes (gains/losses) on the chromosomes.

What is a gene test?

Gene tests look for signs of a disease or disorder in DNA or RNA taken from a person's blood, other body fluids like saliva, or tissues. These tests can look for large changes, such as a gene that has a section missing or added, or small changes, such as a missing, added, or altered chemical base (subunit) within the DNA strand. Gene tests may also detect genes with too many copies, individual genes that are too active, genes that are turned off, or genes that are lost entirely.
 

The types of gene tests include:

• DNA sequence analysis, which which examines your DNA make-up, looking for mutations which may increase your risk for certain diseases.
• SNP (single-nucleotide polymorphism) testing, which tests for small variations in your genome that are associated with increased risk for a disease.

What is a biochemical test?

Biochemical tests look at the amounts or activities of key proteins. Since genes contain the DNA code for making proteins, abnormal amounts or activities of proteins can signal genes that are not working normally. These types of tests are often used for new-born screening.

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What should I expect from a genetic test?

 
Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a medical procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. Alternatively, a small amount of saline mouthwash may be swished in the mouth to collect the cells. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person's doctor or genetic counselor. 
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What do the results mean?

 
The results of genetic tests are not always straightforward, making interpretation challenging, this is why a geneticist will consider not only the test results, but also a person’s medical history, family history, and the type of genetic test that was done.
 

A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Because family members have some genetic material in common, a positive test result may also have implications for relatives. It is important to note that a positive result cannot always establish the exact risk of developing a disorder or its severity.
 

A negative test result means that the laboratory did not find any abnormality of the gene, chromosome, or protein under consideration. Depending on the type of test, further testing may be required, as not all genetic changes that can cause a particular disorder can be detected.
 

A result may also be uninformative, indeterminate, inconclusive, or ambiguous. This can occur because everyone has common, innocent variations in their DNA, called polymorphisms that do not affect our health. In some cases, testing other affected and unaffected family members can help clarify this type of result.
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What are the risks and limitations of genetic testing?

 
The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek).

Rapid advances in genetic medicine are constantly improving doctors' ability to detect mutations and diagnose disorders.
 
However, genetic testing does have limitations:

• Genetic testing cannot always predict the severity of a disease.
• Lab errors are rare but can occur. Therefore, it is important to choose a reputable testing facility.
• There are still many genetic disorders for which genetic tests have not yet been developed.
• Genetic test results are not always straightforward, and interpreting them can be challenging even for a trained medical professional.
• People may feel angry, depressed, anxious, or guilty about their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested.
  
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