Genetics Overview for Providers

Genetics Overview for Providers


Humans take great pride in identifying distinguishing traits from one generation to the next. We enjoy speculating on the resemblance of children to their parents and question which child has, for example, the father’s eyebrows or the mother’s chin. With such observations begins the study of genetics and the submicroscopic structures known as genes…There is probably some genetic component in almost all disease processes, but the extent of this component varies.” – Jerry L. Northern & Marion P. Downs

Nearly 3000 genetic disorders have been identified. Of the…babies born in the United States each year, 2-3% have a major genetic or congenital disease. The average person has 4-8 potentially harmful genes.” – Jerry L. Northern & Marion P. Downs

Identification of genes that are responsible for inherited disorders has become commonplace, if not mundane; and genetic factors in common disorders are coming to light. The promise of genetics in medicine is still largely unappreciated, but this…is changing. Genetics used to be viewed as the discipline that studied rare disorders. Now genetics is recognized as an integral part of oncology,… cardiology and neurology; eventually it will leave no area untouched.” – Bruce R. Korf

Genetics affects each and every one of us. As health care professionals, the chance that genetics will become part of our practice and patient care is increasing every day.

This brief genetics review has been designed to provide an overview of certain genetics terminology and concepts that will likely come up throughout this website, in your work, and in each of our lives.



Genetics refers to the study of genes and chromosomes, and how traits and conditions are inherited and passed through families.

Genes and DNA

Genes are the instructions that tell the cells in our bodies how to grow and function. Genes are often thought of as an instruction manual or blueprint for how we develop and who we are. We all have two copies of almost all of the genes in our bodies, and each of our millions of cells contains one full set of all of our genes. We receive one copy of each of our genes from our mother, and one copy of each of our genes from our father. Similarly, if an individual has offspring, they pass one member of each gene pair onto each child.

Genes are made of a molecule called deoxyribonucleic acid (DNA). DNA is the basic unit of heredity. DNA is composed of four units (called base pairs): Adenine (A); Cytosine (C); Guanine (G); and Thymine (T). The four units that make up DNA are like the 26 letters of the English alphabet. The sequence, or specific order, of these bases spells out instructions for the body to make certain proteins, or carry out certain functions (like how the 26 letters of the English alphabet are put together in specific orders to create words and sentences). The letters of DNA make up our genetic code.

The figure below shows the relationship between a cell, chromosome, DNA, gene, and bases. Chromosomes will be discussed later in this review.

DNA has a double helix structure, which is sometimes described as a twisted ladder. The “sides” of the DNA ladder are made of phosphate and sugar, and the “rungs” are made of base pairs. A always pairs with T, and C always pairs with G. Base pairs are also used as a unit of measure to indicate a length of DNA, or the size of a gene. For example, a gene or piece of DNA that is 10bp long consists of 10 base pairs, whereas a gene or piece of DNA that is 2Kb long consists of 2000 base pairs.

Genes and Proteins

The genetic code of DNA tells the body to make certain proteins. From DNA, a complimentary molecule called ribonucleic acid (RNA) is made, and from RNA, proteins are made. Thus, RNA is the intermediate molecule between DNA and protein; in other words, it helps to translate the instructions of DNA into real proteins.

Proteins are the molecules in our body that make up the parts of our body, and that carry out jobs in our body. For example, our tissues and organs are all made up of proteins. In addition, enzymes, hormones and antibodies are all specific types of proteins. The smaller units of protein are called amino acids. There are over 100 different amino acids in nature, but our bodies use only 20 amino acids to make all of their proteins.

Alleles, Genotypes and Phenotypes

Recall that we have two copies of each of our genes. Alleles refer to the different forms of a gene. For example, a difference in the sequence of bases between two copies of a gene would mean that these two copies are different alleles (different forms of the gene). Different alleles of the same gene may code for different forms of a protein. Sometimes, however, different alleles will not affect the protein they code.

When a person is a heterozygote for a certain gene (heterozygous for a gene), this means that their two copies of this gene are different from each other. When a person is a homozygote for a certain gene (homozygous for a gene), this means that their two copies of this gene are the same.

Genotype refers to all of the alleles of all of the genes that a person has. More broadly, the genotype of an individual is their total genetic makeup. Phenotype, on the other hand, refers to the physical characteristics of an individual. These characteristics may be ones that are visible to the eye (such as hair color, eye color, and height), or they may be internal or biochemical (such as blood pressure and IQ). The phenotype of a person results from their genotype, often in combination with their environment.

The terms allele, heterozygous, homozygous, genotype and phenotype are explained in the following figure. Dominant and recessive will be reviewed later. Please note that this illustration depicts a simplified example of eye color inheritance.



mutation is any change in the usual sequence of DNA. For example, suppose part of a gene usually has the sequence GTAC. If the sequence in a copy of the gene was GTTC, this change from A to T would be considered a mutation. Some mutations cause conditions, others contribute to the healthy diversity between all people, and still other mutations do not cause any change and do not affect the person who has them at all. Whether or not a mutation has any effect depends upon whether it affects the form or function of the protein it codes for.

The causes of mutations are often unknown. Mutations in the genes of a person’s germline (eggs and sperm, as opposed to mutations in non-sex cells), can be passed down to their offspring. On the other hand, some of the mutations we are born with likely occurred just by chance. Still other mutations may be caused by things such as the environment (sun, radiation, or chemicals) or aging.


Polymorphisms refer to a change (mutation) in the DNA sequence that is present in at least one percent of the population. Polymorphisms are generally considered to be “normal” variations in the sequence of DNA, and are generally not considered harmful. One example of a polymorphism is in the hair color gene. Slight changes in the DNA sequence code for different hair. Other polymorphisms do not cause any visible or significant change in the people who have them.



Chromosomes are composed of DNA, and are tiny structures in the nucleus of our cells. Our genes are packaged into chromosomes, and so genes are located all along each of our chromosomes.

In humans, there is usually a total of 46 chromosomes (23 pairs) in each cell. 44 of these chromosomes (22 pairs) are called autosomes, which means that they are the same in both males and females. The final pair of chromosomes are called the sex chromosomes. Females have two X chromosomes, and males have one X chromosome and one Y chromosome.


When chromosomes are studied in the laboratory, they are usually put into order (by pair, size and shape) to make an organized chromosome picture called a karyotype. A karyotype allows cytogeneticists (scientists who study chromosomes) to see whether an individual has any extra or missing genetic material, or any rearrangements in their chromosomes that are large enough to be seen. A karyotype does not allow for changes in individual genes to be seen.

Normal Female Karyotype: 46,XX

Normal Male Karyotype: 46,XY

Chromosome Segregation

As with gene pairs, we each receive one member of each chromosome pair from our mother, and the other member of each pair from our father. Similarly, when we have offspring, we pass one member of each of our chromosome pairs to each of our offspring. When a male passes on an X chromosome, the offspring will be female, and when he passes on a Y chromosome, the offspring will be male.

The figure to the right shows the transmission of chromosomes (and therefore genes) from parents to children.

In this figure, three pairs of chromosomes are shown:
pair #1 (green);
pair #2 (yellow);
pair #3 – sex chromosomes (pink and blue).

The father’s chromosomes are shown in solid color, and the mother’s are striped. Children randomly get one member of each chromosome pair from their mother (striped) and one member of each pair from their father (solid). Daughters get an X from their mother (striped) and an X from their father (solid). Sons get an X from their mother (striped) and a Y from their father (solid).

Chromosome Nomenclature

When karyotypes are complete, the chromosome makeup of an individual is written as:
46, XX for a normal female; and 46, XY for a normal male. The number refers to the total number of chromosomes in each cell, and the letters refer to the sex chromosomes. Additional notation is added when there is a difference from the usual chromosome complement.

There is also a specific way in which a particular spot or region on a chromosome is written; this is used to refer to the particular location of a gene on a chromosome.

The figure on the left is called an ideogram;
this simply means that it is a drawing of a
chromosome with locations labeled. The shorter
arm of the chromosomes is labeled p, and the
longer arm is labeled q. Along each arm are
numbers that indicate specific spots along the


An example of a gene location on a chromosome is 17q21. This refers to a gene located on the long (q) arm of chromosome 17. The 21 following the q refers to the exact spot of the gene on that arm of the chromosome. 17q21 is the location of the BRCA1 gene, which is associated with an increased risk of breast, ovarian and prostate cancers.

The Human Genome Project has been working towards the goal of mapping (determining the location of) all genes in the human genome. A genetic map is a map of the location of genes relative to each other on the chromosome. (Genetic maps are also called linkage maps.)


Inheritance patterns describe the ways in which traits or conditions are passed through families. The various patterns of inheritance are described in the following pages.

Autosomal Recessive Inheritance

Autosomal means that the changed gene is located on an autosome (non-sex chromosome), so males and females are equally likely to be affected. Recessive means that both copies of the gene must be changed in order for a person to have the condition. In autosomal recessive inheritance, a person must inherit two copies of a particular form of a gene in order to show the trait or have the condition. PKU is an example of a disorder that is inherited in an autosomal recessive manner.

The figure to the right shows that for conditions inherited in an autosomal recessive manner, both copies of the gene must be altered (mutated) and not working in order for a person to have the condition. If a person has a mutation in only one copy of the gene, they are a carrier and are not affected with the condition.

Autosomal Recessive
The figure above shows that two parents who are carriers of an autosomal recessive condition have a 25% (1 in 4) chance of each child inheriting the condition.

Autosomal Dominant Inheritance

Autosomal means that the changed gene is located on an autosome (non-sex chromosome), so males and females are equally likely to be affected. Dominant means that only one copy of the “dominant” gene needs to be changed in order for a person to have the condition. In other words, although genes are always in pairs, a person needs to inherit only one copy of a particular form of a gene in order to have an autosomal dominant condition. Huntington’s disease is an example of a disorder inherited in an autosomal dominant manner.

The figure to the right shows that for conditions inherited in an autosomal dominant manner, only one copy of the gene needs to be altered (mutated) in order for a person to have the condition.


Autosomal Dominant Inheritance

The figure above shows that when an individual with an autosomal dominant condition has a child with an individual who does not have the condition, each of their children has a 50% (1 in 2) chance of having the condition

X-linked Inheritance

X-linked inheritance refers to conditions or traits for which the gene is located on the X chromosome. Recall that females have two X chromosomes while males have only one X chromosome.

The majority of X-linked conditions are X-linked recessive, meaning that one normal (working) copy of the gene would compensate for a non-working copy. It is much more common for males to have X-linked recessive conditions than females, since males do not have a second copy of their X chromosome to compensate if their one copy has a mutation. There are some cases when females can be affected with an X-linked recessive condition, but this is much less common.

X-linked dominant inheritance is quite rare.

The figure to the right shows that females will only be affected with an X-linked recessive condition if both copies of the gene on their X chromosome have mutations (this is quite rare). If a female has a mutation in only one copy of the gene on their X chromosome, they will not have the condition. Males, on the other hand, will have the condition when the gene on their one X chromosome has a mutation, since they do not have a second copy to compensate.

X-linked Inheritance

The figure above shows that when a women is a carrier of an X-linked recessive condition and has a child with a man who does not have the condition, each of their male children has a 50% (1 in 2) chance of having the condition and each of their female children has a 50% (1 in 2) chance of being a carrier of the condition.

When a female is a carrier of an X-linked recessive condition (i.e., has a mutation in one copy of an X-linked gene), each of her offspring will have a 50% (1 in 2) chance of inheriting the working copy, and a 50% (1 in 2) chance of inheriting the non-working copy. Thus, daughters of a female carrier have a 50% chance of being a carrier and a 50% chance of being a non-carrier, and sons have a 50% chance of being affected and a 50% chance of not being affected.

When a male has an X-linked condition, all of his daughters will be carriers (since all female offspring receive an X from their father), and none of his sons will be affected (since he will pass on his Y chromosome to all of his sons).

Mitochondrial / Maternal Inheritance

The normal 46 chromosomes in our body are contained in the center of the cell, which is called the nucleus. Mitochondria are structures located in the cytoplasm of the cell outside of the nucleus. Mitochondria also contain genes that are separate from the ones in the nucleus, although the mitochondrial DNA is one long string of genes and is not arranged as chromosomes. Mitochondria are organelles that provide much of the energy cells used for the work they do. All of the mitochondria in a person’s cells descend from the mitochondria present in the original egg from that person’s conception. The sperm does not contribute any mitochondria to the baby.

Thus, an individual’s mitochondria are only inherited from his or her mother. This pattern of inheritance is called mitochondrial or maternal inheritance. An abnormality in one of the mitochondrial genes can therefore be passed by the mother in her egg cells. Because mitochondria can be inherited only from a mother’s egg, mitochondrial genes show a very distinct pattern of inheritance: Both males and females can be affected with a mitochondrial disease gene, but only females can transmit that mitochondrial disease gene to children.

Multifactorial Inheritance

Many conditions are caused by a combination of genes and other factors, such as the environment. These conditions are said to be “multifactorial.”  People who have such a condition are often born into families with no other affected people. Parents of a child with the condition have a greater chance of having another child with the condition than couples who do not have a child with the condition.

Mutifactorial inheritance is actually the most common form of inheritance; most traits and characteristics are inherited in a multifactorial fashion.

This figure above shows that a certain combination of genetic and environmental factors is needed in order for a person to be affected with a multifactorial condition.


Genetic Testing

A genetic test involves looking at the letters that make up the instructions of a person’s code of DNA (genes) to see if certain mutations (changes) are present. A person’s genes are usually looked at from a small sample of blood. Genes can also be examined from other body tissues, such as a cheek swab, or a tissue sample.

There are two overall types of genetic testing: DNA Sequencing; and Mutation Analysis.

In “DNA sequencing,” the DNA code of letters is read along the entire gene (or for a certain part of it). In this way, any changes in the spelling of the gene’s instructions will be seen. In some cases, a change may be found that is known to be associated with a condition or an increased risk for a condition. In other cases, there may not be any changes found. In still other cases, a change may be found, but the meaning of this change may not be known at this time.

In “mutation analysis,”  testing is done to look at a specific region of a gene, rather than reading the code all along a gene. Mutation testing is usually done if the mutation in a family is already known, or if there are certain mutations that are usually associated with a condition.

What are Some Benefits of Genetic Testing?

If a mutation (change) is detected, it may explain why the person has the condition. In some cases, knowing what mutation a person has will allow doctors to predict how severe the condition might become and what other symptoms may be expected. This may allow the person’s medical care to be adjusted accordingly. Knowing the mutation responsible will also predict the chances that future children may inherit the condition from the parent. Prenatal testing (testing a baby before it is born to see if it has the mutation) may also be possible.

What are Some Limitations of Genetic Testing?

Not all of the genes that are involved in conditions are known, so even if a condition runs in the family, it may not be possible to find the mutation involved.

Likewise, a negative result (no change is found) does not guarantee that the person will not get the condition. The person may have a different mutation that was not detectable by the test used, or the person may have a mutation in a different gene that also causes the same condition.

Genetic tests are different from other medical tests in that the results may provide information about other members of the family, and not just the person being tested. In addition, some people are concerned about keeping the results of their genetic testing private. Test results should not be seen by anyone who is not involved in the testing, unless permission is obtained.

Genetic Screening

Screening is the process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is generally to catch the disease in its early stages. It is important to note that with most screening, follow up testing is required to confirm a diagnosis.

Below are the possible results of screening

Possible Results True Positive True Negative False Positive False Negative
Person’s health status Person HAS the disease Person does NOT have the disease Person does NOT have the disease Person HAS the disease
Test Result Confirms that person HAS the disease Confirms that person does NOT have the disease Test results say that person HAS the disease. Test says that the person does NOT have the disease

Genetics Evaluation

Below are definitions of a few terms related to the Genetics Evaluation.

geneticist is a medical doctor with a specialty in genetics. A genetic counselor is a healthcare professional who provides information and support to individuals and families who have a genetic disorder, might be at risk for developing an inherited condition, or are concerned that they may have a child with an inherited disease. The geneticist and genetic counselor work together to obtain and analyze family medical histories, and calculate and explain people’s risks, options, and testing results.

pedigree is a medical drawing of a family tree that includes all of a person’s close relatives, the relationship between family members, and health information. A pedigree is used by health care professionals to analyze a family for conditions which certain family members may have or be at risk for.

Pedigrees also show the relationship between individuals in a family. Males in a pedigree are indicated by squares, and females are indicated by circles. The lines between individuals enable us to see the relationship between them.

A Few Final Terms

  • Congenital refers to features or conditions that a baby is born with, as opposed to conditions that develop later in life. For example, congenital hearing loss is hearing loss which a baby is born with compared to hearing loss due to old age.
  • Acquired means that a feature or condition developed later in life.
  • Syndromic refers to a group of symptoms and clinical findings that, when found together in a single individual, make up a particular condition or disease.
  • Nonsyndromicmeans that a person does not have any other symptoms other than an isolated clinical finding. Nonsyndromic cleft lip, for example, is an isolated birth defect without any other symptoms.
  • Familial indicates a disease or clinical finding that runs in the family. In other words, a familial condition is one in which more that one family member is affected.
  • Sporadic refers to a condition that does not run in the family. Its occurrence is isolated and is limited to only one family member.