Learn More About Genetics

by Sharon Aufox, M.S., C.G.C.

This information is intended to provide you with a brief review of some of the basic concepts in genetics. If you would like more detailed information, please refer to the references section for other resources. If you have concerns about a family history of a particular genetic condition and/or are interested in finding out if genetic testing is available, please contact your physician or local genetic counselor.

The information contained on this web site is intended to be used as a general information source. It is not intended to be used as a substitute for consultation with your health care provider.

The Cell

Large organisms are comprised of multiple cells. In humans, each cell is composed of several components. Each of these components has a specific job to make sure the cell functions properly. The “brain” of the cell is called the nucleus. Every nucleus contains a complete set of genetic instructions (called a genome).

DNA

DNA stands for deoxyribonucleic acid. It is DNA that carries the instructions that help dictate how an organism will grow and develop. DNA is found in the cell’s nucleus and is the genetic information that is transmitted from a parent to a child.

DNA resembles a twisted ladder, which is called a double helix. The steps of this ladder are made up of structures called bases. There are four different bases that make up the “steps” of the DNA double helix. These four bases are called adenine (A), thymine (T), cytosine (C), and guanine (G). Each base is paired with another base to create the “steps” of the DNA strand. Bases “A” and “T” can only be paired together and bases “C” and “G” can only be paired together. It is the arrangement of these base pairs, called a sequence, which are the genetic instructions that creates a particular organism.

Genes

Genes are segments of DNA. What makes one gene different from another is the order of its DNA bases. The specific arrangement of bases in a gene is the “code” or the instructions of how to make a particular protein. Proteins are what perform most of the functions that our body needs to grow and survive.

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Genetics

The field of genetics is the study of how genes impact an organism’s development and how genes are passed from one generation to the next.

Chromosomes

Each DNA strand is packaged into structures called chromosomes. There are thousands of genes located on each chromosome and humans typically have 46 chromosomes in every cell. Those 46 chromosomes can be arranged into 23 pairs, with one chromosome in each pair inherited from the mother and the other chromosome in the pair inherited from the father. To help identify the chromosomes, 22 of the chromosome pairs are numbered (1-22). The twenty-third pair is the sex chromosomes and they are labeled by letters instead of numbers. Typically, females have two “X” chromosomes and males have one “X” chromosome and one “Y” chromosome. To make it easier to analyze the chromosomes in one cell, the chromosomes are arranged into their pairs and identified by their number or letter. This arrangement of the chromosomes is called a karyotype.

Genetics and Disease

In some way, most diseases have a genetic component. Some of these genetic changes can be inherited from one or both parents, while other genetic changes can occur for the first time in an individual. Genetic changes that occur for the first time in an individual are not inherited from one or both parents. These changes can occur either at the time of that person’s conception or occur during that person’s lifetime.

An individual who has a genetic change that is present from the moment of conception, will have that genetic change in every cell of the body. If the genetic change is in every cell of the body, this means that the genetic change is also present in that individual’s gametes (the egg or sperm). If a genetic change is present in the gametes, then that person will have a chance of passing that genetic change onto his or her children. This type of genetic change is called a germ line mutation.

If a genetic change occurs during an individual’s lifetime, then only the cell where the change occurred and all of it’s daughter cells will carry that change. This type of genetic change, is called a somatic mutation. Somatic mutations are not passed onto the individual’s children. The most common example of a somatic mutation leading to a medical condition is many forms of cancer.

Any change occurring in either the genes or the chromosomes may lead to the development of disease or birth defect. One example is the condition Down syndrome. Individuals with Down syndrome have an extra chromosome 21. This means that instead of having two copies of the 21st chromosome, these individuals have three. The presence of an extra chromosome changes the instructions for how the body will grow and develop. In this case, the presence of an extra chromosome 21 causes the features typically seen in individuals with Down syndrome. Differences in growth and development can also occur when an individual has a chromosome missing or has extra or missing pieces of a chromosome.

Diseases that are caused by a change in one gene (also called mutation) are called monogenic diseases. There are also diseases that are caused by more than one mutated gene (called polygenic diseases) or a combination of a mutated gene or genes and other external factors (called multifactorial conditions).

Monogenic Disease

Monogenic diseases are usually associated with rare conditions and can be inherited in a family in different ways (called patterns of inheritance). Mutations can be a change in a base pair (ex: a “T” is changed to a “G”) or it can be a deletion of one or more base pairs.

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Patterns of Monogenic Inheritance

• Autosomal Dominant
• Autosomal Recessive
• X-Linked Dominant
• X-Linked Recessive

Autosomal Dominant:

An autosomal dominant (AD) condition occurs as the result of a gene mutation that is located on one of the numbered chromosomes (chromosomes 1-22). Each person usually carries two of every chromosome. Therefore, a gene located on one chromosome typically has a duplicate copy located on the other chromosome in the pair. An autosomal dominant condition occurs when there is a mutation in one of the two genes in a pair and that mutation either causes the gene to produce a protein that does not function properly or does not produce a protein at all. Although the gene in the pair that does not contain a mutation is still working as expected, an autosomal dominant condition occurs because the human body needs both genes in the pair to function normally.

Depending on the disease and/or the family, an autosomal dominant mutation can either occur for the first time in an individual or be inherited from a parent. Typically, an individual who has an autosomal dominant condition has a 50% (1 in 2) chance to pass the condition on every time he/she has a child. This means that there is also a 50% chance for an affected parent to not pass the condition on with each pregnancy.

All autosomal dominant conditions can have a range of symptoms and severity. With several autosomal dominant conditions, some affected individuals can show more severe symptoms or different symptoms than other affected individuals with the same condition. This is called variable expressivity. In some autosomal dominant conditions, variable expressivity can be seen in affected members within the same family. There are some people who have an autosomal dominant mutation, but do not show signs of the condition. This phenomenon is called reduced penetrance. Differences in penetrance can even be seen among affected individuals in the same family.

Examples of Autosomal Dominant Conditions:

Achondroplasia: The most common form of dwarfism, characterized by short arms and legs, average-sized torso and slightly larger head with a prominent forehead. For more information, please go to the Little People of America’s web site (http://www.lpaonline.org/) .

Autosomal Dominant Polycystic Kidney Disease (ADPKD): This is a condition that causes multiple cysts to develop on each kidney. Over time, the cysts continue to multiply and grow, causing the kidneys to become enlarged. Eventually, the kidney stops working, causing end-stage renal disease. For more information, please go to the PKD Foundation’s web site (http://www.pkdcure.org/) .

Autosomal Recessive:

Genes are packaged in chromosomes. Therefore, like chromosomes, most of a person's genes are inherited in pairs, one member of each pair coming from each parent. An autosomal recessive condition is one in which both members of a gene pair must be altered (or mutated) in order for the individual to be affected with the associated condition. If an individual has at least one non altered copy of the gene, he/she will not be affected with the associated disease.

An individual who has one altered gene and one non altered gene in a pair is called a carrier. Carriers do not typically have symptoms of the genetic condition, but are at risk to pass the altered gene to their offspring. In order for an individual to be affected with an autosomal recessive condition, both of his/her parents must have at least one copy of the altered gene; that is, either be a carrier or an affected individual.

A child is at risk to inherit an autosomal recessive disease only when BOTH parents are carriers of the same condition. When both parents are carriers, there is a 25% (1 in 4) chance, each time they have a child, for that child to inherit the autosomal recessive disease.

Examples of Autosomal Recessive Conditions:

Cystic Fibrosis: A condition that affects how the lungs and pancreas function, causing life-long digestive and breathing problems. For more information, please go to the Cystic Fibrosis Foundation’s web site (http://www.cff.org) .

Sickle Cell Anemia: A condition that causes the red blood cells to not form properly, resulting in several health problems including anemia, an increased risk of developing infections, and joint pain. For more information, please go to the Sickle Cell Disease Association of America, Inc. (http://www.sicklecelldisease.org/)

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X-Linked Dominant:

X-linked Dominant conditions (XD) are caused by a mutated gene located on the X chromosome. As with autosomal dominant conditions, only one gene needs to contain a mutation in order to cause the individual to develop the disease. Females and males are affected differently by X-linked dominant conditions because the X chromosome is one of the sex chromosomes, with females typically having two X chromosomes and males typically have one X and one Y chromosome. A characteristic of XD diseases is that usually females are affected with the disease. Males who inherit a XD condition often die prior to or soon after birth. There are some XD conditions where affected males do survive, but they usually have an extremely severe form of the disease.

X-linked dominant mutations can be inherited or occur for the first time in an individual. Women who are affected with an XD condition have a 50% (1 in 2) chance to have a daughter who is also affected with the condition and a 50% (1 in 2) chance to have a son inherit the mutation. This also means that an affected woman has a 50% chance to have a child who does not inherit the mutation. Women who are affected with an XD condition also exhibit variable expression in their symptoms.

Example of an X-Linked Dominant Condition:

Incontinentia Pigment: A condition that causes differences with the hair, skin color, eyes, teeth, and bones. For more information, please go to the Incontinentia Pigmenti International Foundation’s web site (http://www.imgen.bcm.tmc.edu/molgen/index.html) .

X-Linked Recessive:

X-linked recessive conditions (XR) are also caused by a gene located on the X chromosome. However, unlike X-linked dominant conditions, males are typically affected while females are either unaffected or mildly affected. Since females typically have two X chromosomes, a mutation located on one of the X chromosomes is usually not enough to cause the female to have symptoms of the disease. However, since males usually have one X chromosome, if they inherit the X chromosome containing the mutated gene, they will develop symptoms of the disease.

XR mutations can occur for the first time at the time of conception of a male child or be inherited from the mother. XR diseases that are inherited in a family usually pass from mother to son. Fathers who are affected with XR conditions cannot pass the condition on to their sons. However, they will always (100% of the time) pass on their X chromosome containing the mutated gene to their daughters. Mothers who are carriers of XR diseases will have a 50% (1 in 2) chance of having an affected son and 50% (1 in 2) chance of having a daughter who would also be a carrier of the disease.

Examples of X-Linked Recessive Conditions:

Hemophilia: A condition when individuals have difficulty forming blood clots. For more information, please see the National Hemophilia Foundation’s web site (http://www.hemophilia.org/) .

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Red/Green Color blindness: Is the most common form of inherited colorblindness. Individuals with red/green color blindness have difficulty seeing the color red, or the color green or mixtures of these colors. For more information, please see WebMD’s (http://www.webmd.com) information on color blindness.

Polygenic Conditions

Polygenic conditions are features, health conditions, and diseases that are the result of the interaction of two or more genes. For example, eye color, which was once thought to be the result of autosomal recessive inheritance, is now known to be due to the combination of several genes. This is based on the observation of several blue-eyed parents having brown-eyed children and individuals, with either blue or green colored eyes, also having spots or flecks of another color (usually brown).

Multifactorial Inheritance

There are also diseases and birth defects that appear to be more prevalent in certain families, but do not seem to follow any of the traditional patterns of inheritance of monogenic (single gene) disease. These are called multifactorial disorders. A multifactorial condition or birth defect is influenced by other genes as well as non-genetic factors, such as environmental exposures or lifestyle choices. Examples of conditions with multifactorial inheritance include diabetes, heart disease, and cancer.

Polymorphisms

Some genetic changes are common in the population and do not appear to cause a disease by themselves. These genetic changes or variants are called polymorphisms. While polymorphisms may not directly cause a disease like the mutations seen in monogenic disorders, some polymorphisms, either in combination with other factors, like environmental factors, or with other polymorphisms, can affect the chance that an individual may develop a condition or possibly affect how they would react to certain medications or treatments.

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Genetic Counselors

Genetic counselors are health professionals with specialized graduate degrees and experience in the areas of medical genetics and counseling. Most enter the field from a variety of disciplines, including biology, genetics, nursing, psychology, public health, and social work.

Genetic counselors work as members of a health care team, providing information and support to families who have members with birth defects or genetic disorders and to families who may be at risk for a variety of inherited conditions. They identify families at risk, investigate the problem present in the family, interpret information about the disorder, analyze inheritance patterns and the risk of recurrence and review available options with the family.

Genetic counselors also provide supportive counseling to families, serve as patient advocates, and refer individuals and families to community or state support services. They serve as educators and resource people for other health care professionals and for the general public. Some counselors also work in administrative capacities. Many engage in research activities related to the field of medical genetics and genetic counseling.

Adopted by the National Society of Genetic Counselors, Inc. 1983. From the National Society of Genetic Counselors

For more information on genetic counseling, or to locate a genetic counselor in your area, please visit the National Society of Genetic Counselors's web site (http://www.nsgc.org/) .

References

1. Alberts, Bruce, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts, and James D. Watson, Molecular Biology of the Cell, 3rd edition. New York: Garland Publishing, 1994.
2. Cooper, Geoffrey M., The Cell: A Molecular Approach, 2nd edition. Sunderland, Massachusetts: Sinauer Associates, Inc., 2000.
3. Griffiths, Anthony J. F., Jeffrey H. Miller, David T. Suzuki, Richard C. Lewontin, and William M. Gelbart, An Introduction to Genetic Analysis, 7th edition. New York: W. H. Freeman & Co., 2000.
4. Griffiths, Anthony J. F., William Gelbart, Jeffrey H. Miller, and Richard C. Lewontin, Modern Genetic Analysis. New York: W. H. Freeman & Co., 1999.
5. Lodish, Harvey, Arnold Berk, Lawrence S. Zipursky, Paul Matsudaira, David Baltimore, and James Darnell, Molecular Cell Biology, 4th edition. New York: W. H. Freeman & Co., 2000.
6. Nussbaum, Robert L., Roderick R. McInnes, and Huntington F. Willard, Thompson & Thompson, Genetics in Medicine, 6th edition. Philadelphia: W. B. Saunders Company, 2001.

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