Myths and Misconceptions about Heredity

There are many myths and misconceptions about heredity and the cause of birth defects and genetic conditions. Robin Bennett, MS., author of "The Practical Guide to The Genetic Family History", Wiley-Liss, 1999, captures a number of these with the list below:

• If no one else in the family is affected, the condition is not inherited. FALSE. One may be the first person in a family to be affected with a particular genetic disorder.
• If several people in the family have the condition, it must be inherited. FALSE. Some conditions are more strongly environmental, or occur by chance alone.
• All birth defects are inherited. FALSE. Birth defects are "congenital" (present at birth), but have a variety of causes. Some are strongly environmental or sporadic.
• The parents (especially the mother) must have done something before or during the pregnancy to cause the condition in the child. FALSE. Birth defects have a variety of causes. Regarding genetic conditions, parents have no control over the genes they pass to their children.
• With 25% recurrence risk, after one child is affected, the next three will be unaffected. FALSE. With every pregnancy, the odds are the same.
• With a 50% recurrence risk, every other child is affected. FALSE. With every pregnancy, the odds are the same.
• Birth order influences disease status. FALSE. Each pregnancy is independent of any other.
• If the affected individuals in the family are all women or all men, the condition must be sex-linked. FALSE. This may occur by chance alone.
• A person will inherit the condition because he or she “looks” or “acts” like the affected relative(s). Or the opposite. FALSE. This may occur by chance alone.
• For a condition with sex-influenced expression, individuals of the opposite sex cannot transmit the condition (ie male cannot pass gene for breast cancer). FALSE. In some conditions, one sex may be more likely to be affected than the other, but in many cases the gene for the condition may be passed by either sex.

 

How Genes Work

The Structure of Cells and DNA

• Most body cells contain a nucleus
• The nucleus contains DNA
• DNA is a long molecule made of units called bases
• Bases come in four types, labled A, T, G, and C
• The bases pair together to form a double-strand of DNA
• The double strand twists into what is called a helix
• The helix is folded up and packaged inside what are called chromosomes

Click on the picture to enlarge.

 

Your Chromosomes

• Humans have 46 chromosomes, which come in 23 pairs. One of each pair has been inherited from your mother, one from your father.
• 22 of the 23 pairs are identical in both males and females, the 23rd pair is known as the sex chromosomes. Females have two X chromosomes, while males have one X chromosome and one Y chromosome.

 

Click on the picture to enlarge.

A chromosome abnormality happens when a baby is born with some change in the number or structure of the chromosomes. This leads to the individual having extra or missing chromosomal material, known as a chromosome abnormality. Many chromosome abnormalities cause birth defects and mental retardation.

Down syndrome is the most common chromosomal disorder. It happens in about 1 out of every 800 births. Down syndrome is also known as trisomy 21. It occurs when there is an extra, or third copy of chromosome #21. Features of Down syndrome include moderate mental retardation and a typical facial appearance. About 40% of individuals with Down syndrome also have heart defects. Other less common chromosome abnormalities may be more or less severe than Down syndrome.

Other chromosome abnormalities

Trisomy 18 and trisomy 13 are other chromosome abnormalities. They occur in about 1/4000 births. They are caused by an extra, or third copy of chromosome number 18 or 13 in all of the cells in the body. The extra copy of chromosome 18 or 13 is present from the time of conception. Babies with trisomy 18 and 13 have many birth defects including heart, brain, and kidney abnormalities. Babies with trisomy 18 and 13 seldom live longer than a few days or weeks. Many die before they are born.

Chance of Having a Baby with a Chromosome Abnormality

Most chromosome abnormalities (including most cases of Down syndrome) are not hereditary, that is, they do not run in families. Older women have a greater risk than younger women for having a baby with a chromosome abnormality. Although the risk gradually increases with age, a woman of any age can have a baby with a chromosome abnormality.

The following chart shows the approximate chances of having a baby with a chromosome abnormality:

Mother's Age at Due Date	Approximate chance of a having a baby with a chromosome abnormality
20	1/525
25	1/475
30	1/400
35	1/200
36	1/165
37	1/125
38	1/100
39	1/80
40	1/65
41	1/50
42	1/40
43	1/30
44	1/25
>45	1/20

 

The Gene's Role

• All the cells in the body contain the same set of 46 chromosomes. Each chromosome contains thousands of genes that direct the structure and function of each cell in the body.
• The function of genes is to make proteins. Each gene makes a protein that has a specific function in the cell.
• Different genes are activated in different cells. For example, genes that code for brain function are active in brain cells, and not active in liver cells. Genes that code for liver function are active in liver, not brain cells.

 

How Genes Change or Mutate

• Genes are constantly undergoing change. A change in the order of the base pairs is known as a “mutation”. A mutation is similar to a spelling error. You can change the spelling of a word and still be able to tell what word it is. Like so, many gene mutations have no affect on the function of the gene.
• In our analogy, sometimes the spelling is so wrong that you cannot tell what word it was supposed to be. Likewise, other gene mutations alter the gene’s function. Remember that a gene produces proteins. A mutation that alters the genes ability to produce a protein that functions normally, or a mutation that reduces the amount of the protein that the gene can make, have significant impact on the body, and may cause disease.
• Since we have two copies of every gene, a mutation can occur in one, the other or both copies of the gene.
• A mutation that occurs in one copy of a pair of genes while the other copy has no mutation is called being “heterozygous”. Heterozygous means 2 (or more) things that are NOT like each other.
• A mutation that occurs in both copies of a pair a genes is called being “homozygous”. Homozygous means that 2 (or more) things that ARE like each others.

 

Your Family History

• Many people wonder about their own chance of developing a disease such as cancer, diabetes or heart disease.
• If your close family members had a certain disease, does that mean that you likely to develop the same condition?
• All families have risk for certain disorders. Everyone possesses a certain number of genes that can cause disease.
• Most people will find themselves at an increased risk for one kind of condition and at a lower risk for others.

 

Your Family Medical History

What Is A Family Tree?

• The family medical tree is a visual picture of your family's medical and health history.
• The family medical history provides another tool for evaluating an individual’s risk for disease.
• When there is a family history of a disease, it may increase the risk for close family members to get that disease.
• If you know you are at risk to get a disease, you may follow specific health recommendations for lowering your risk.

Drawing Your Family Tree

How to Draw Your Family Tree

• Family Tree Example

  Click on the picture to enlarge.

  Use the following example to draw your own family tree. Write your name at the top of your paper and date you drew your family tree. Include your ethnic background.
• See the standardized symbols. In place of the words father, mother etc., write the names of your family members.
• When possible, draw your parents’ brothers and sisters and your brothers and sisters, starting with the oldest to the youngest, going from left to right across the paper.
• If a family member is deceased, record age and cause of death. Be sure to include age of onset and age at death. Include habits of smoking, alcohol or drug use.

  Disorders to Include

Family Tree Legend

Click on the picture to enlarge.

Birth defects Respiratory disease Depression Diabetes Cancer (Include type) Hearing loss Heart disease High cholesterol High blood pressure

Infertility Mental retardation Multiple miscarriages Obesity Osteoporosis Physical abnormalities Stroke Vision impairment Sudden death

Know the Details

Take good documentation of the following conditions:

• Disease/Diagnosis
• Age of onset
• Age at death
• Cause of death

 

Some Interesting Family Trees

 

Autosomal Dominant

Examples: Achondroplasia Marfan syndrome Neurofibromatosis Click on the picture to enlarge. Please see our autosomal dominant inheritance section for more information.

 

Autosomal Recessive

Examples: Sickle cell anemia Tay-Sachs disease Cystic fibrosis Click on the picture to enlarge. Please see our autosomal recessive inheritance section for more information.

 

X-linked Recessive

Examples: Hemophilia Duchenne muscular dystrophy Fragile X syndrome Click on the picture to enlarge. Please see our x-linked recessive inheritance section for more information.

Multifactorial

Examples: Clubfoot Cleft lip/palate Spina bifida Many adult-onset disorders like diabetes, asthma, hypertension, epilepsy. Click on the picture to enlarge. Please see our multifactorial inheritance section for more information.

 

Inheritance Patterns

Introduction to Inheritance Patterns

Autosomal Inheritance

Autosomal Dominant Inheritance

Recurrence Risk for Autosomal Dominant Conditions

Features of Autosomal Dominant Inheritance

Autosomal Recessive Inheritance

Recurrence Risk for Autosomal Recessive Conditions

Carrier Testing for Recessive Disorders

X-Linked Inheritance

X-Linked Recessive Inheritance

X-Linked Dominant Inheritance

Multifactorial Inheritance

Examples of Multifactorial Conditions

Calculation of Risk Figures for Multifactorial Conditions

Prevention of Multifactorial Diseases

Mitochondrial Inheritance

Types of Disease Caused by Mutations in Mitochondrial DNA

Inheritance of Mitochondrial Disorders

 

Introduction to Inheritance Patterns

There are many genetic conditions, and many different ways to inherit them. The following pages discuss the different inheritance patterns. They are: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, multifactorial and mitochondrial inheritance. Autosomal inheritance (either dominant or recessive) can occur equally in males and females, whereas X-linked inheritance depends specifically on the sex of the individual. Multifactorial inheritance involves genes from both sides of the family, as well as the influence of environmental factors. Mitochondrial inheritance is passed solely from mothers to children as mitochondria are located in maternal egg cells, and not in sperm cells. All of these inheritance patterns can be very confusing, and sometimes conditions can be inherited in more than one way.

If you feel that you would like to ask more specific questions about a condition in your own family and the mode or modes of inheritance, please call the Genetics Department closest to you for a confidential consultation.

 

Autosomal Inheritance

Autosomal inheritance refers to inheritance of single gene disorders found on the autosomes. The autosomes include all the chromosomes except for the sex chromosomes. Humans typically have 22 pairs of autosomes and 1 pair of sex chromosomes giving a total of 46 chromosomes. This means individuals typically have two copies of each gene.

 

Autosomal Dominant Inheritance

Autosomal dominant is a mode of inheritance in which only one copy of a gene is necessary in order to manifest symptoms of a particular condition. Although there are some exceptions, males and females are affected with equal frequency and severity for most dominant conditions. Individuals who inherit two copies of a dominant gene (i.e., both their parents have the condition) usually have a more severe course than that expected when they inherit only one copy. Sometimes the effect of two dominant genes is so severe that the pregnancy will spontaneously abort.

• Recurrence Risk for Autosomal Dominant Conditions - Each child of a person affected with an autosomal dominant condition has a ½ or 50% chance of being affected regardless of sex or birth order. We usually see evidence of the autosomal dominant condition in every generation. This is often referred to as vertical transmission. Individuals within the family who do not inherit the defective dominant gene, will not pass on the gene to their children.

  Sometimes a dominant condition arises spontaneously (meaning it's never before occurred in the family). In this circumstance, the first person diagnosed in a family with the condition developed it as a result of a new change or mutation in either the egg or sperm cell involved in the conception of that person. When this happens, the person does not "inherit" the disorder from anyone, but will have a 50% chance to pass it on. This happens by chance and happens more often for some conditions than for others.

• Features of Autosomal Dominant Inheritance - Other features of autosomal dominant inheritance include variable expressivity, reduced penetrance, and germinal or gonadal mosaicism. Variable expressivity means that individuals who inherit the same gene may develop different features of the condition. These features or symptoms will be related to the condition but not exactly the same for all gene carriers. Reduced penetrance means that not everyone who inherits the gene will develop detectable features. Gonadal mosaicism means that an unaffected person may have a mutation in the gene for the condition in some of his or her germ cells (the cells that develop into an egg or a sperm cell). This person could then pass on the condition to his children although the chance would be less than 50%.

 

Autosomal Recessive Inheritance

Autosomal recessive is a mode of inheritance in which two copies of the gene for the condition are needed to manifest features or symptoms of the condition. Each parent contributes one copy of the gene. In general, males and females are equally likely to develop manifestations of autosomal recessive conditions. In this pattern of inheritance, disorders characteristically appear in members of one generation but not in their parents or in their offspring. This is called horizontal transmission.

The parents of an individual with an autosomal recessive condition are carriers of the condition. Carriers of recessive conditions usually manifest no features of the condition and don't know they are carriers until an affected child is born. It is estimated that each of us carries 5 or 6 conditions or traits that could cause a significant disorder for a child if we had a partner who carried the same trait. The rarer the autosomal recessive condition, the more likely the parents are consanguineous or related by blood.

• Recurrence Risk for Autosomal RecessiveConditions - Each child of known carrier parents has a ¼ or 25% chance of developing the condition regardless of sex or birth order. Each child has a ½ or 50% chance of being a carrier themselves. Each child has a ¼ or 25% chance of carrying no copies of the gene for the condition.

  Each child of an affected individual will carry one copy of the gene. If the affected person marries a carrier, then each child will have a ½ or 50% chance of developing the condition. If the affected person marries an individual who doesn't carry the gene, then all their children will be carriers but none will be affected with the condition.

• Carrier Testing for Autosomal Recessive Disorders - Carrier testing for conditions more commonly found in certain ethnic groups such as Tay-Sachs Disease, Canavan Disease, Sickle Cell Disease, Thalessemia, and Cystic Fibrosis is available in specific clinical situations.

 

X-Linked Inheritance

X-linked inheritance refers to inheriting traits which are determined by genes that are located on the "X" chromosome only and not the other 22 pairs of chromosome known as autosomes. Women are born with two "X" chromosomes and men with an " X" and a "Y" chromosome. Most people think of X-linked recessive conditions when they think of X-linked conditions as the males are affected and the females are carriers and not affected , common X-linked recessive conditions include Hemophilia or Duchenne's Muscular Dystrophy. There are also a few conditions where women are affected and males do not survive; this pattern of inheritance is known as X-linked dominant. Below are more detailed descriptions of the two forms of X-linked inheritance.

X-linked recessive:: Inheritance that leads to a condition that is expressed by all males who have the altered gene on their "X" chromosome. Since males have only one "X" chromosome, they have an altered gene on the "X" chromosome and it will be expressed (ie. hemophilia, colorblindness). Women who "carry" an altered gene on one of their two "X" chromosomes also have a comparable and unaltered gene on their other "X" chromosome and can pass the gene onto 50 % of their sons and 50 % of their daughters. Women usually do not express any symptoms of the condition as they have the usual "X" chromosome with the information necessary in addition to the "X" with the altered gene. Men with an X-linked recessive condition will pass their altered "X" to all of their daughters who will then be carriers of the condition. None of the sons born to a man with an X-linked condition will have the same condition as the father.

X-linked dominant:: Inheritance that leads to a condition where the individual receives an altered copy of the gene and expresses the condition whether they are male or female. An affected male can transmit the altered gene to all of his daughters and none of his sons (they receive his "Y" chromosome). As the condition is dominant, the women who have the altered gene do express the condition. Some of these X-linked dominant conditions are lethal in males so it appears that women only pass the condition to 50 % of their daughters as the male babies who inherit the gene are miscarried or stillborn (ie. Incontinentia pigmenti, Goltz syndrome).

This information can be difficult to understand. A genetic counselor can help you understand the implications of various conditions in your family. For specific questions, we ask that you call us directly. Please call the Kaiser Permanente Genetics Department closest to you.

 

Multifactorial Inheritance

Many common adult human diseases, such as cancer, heart disease, and diabetes have genetic components. It is believed, however, that these diseases are caused by the cumulative effect of multiple genes. It is also known that these genes interact with the environment to affect expression of the disease or human trait in question. Multifactorial inheritance is the term used to describe this interplay of genetic and environmental factors.

• Examples of Multifactorial Conditions - Examples of multifactorial conditions that are present at birth include cleft lip and palate, pyloric stenosis, hip dislocations, heart defects and neural tube defects such as spina bifida.

• Calculation of Risk Figures for Multifactorial Conditions - Risk figures for multifactorial conditions are obtained by studying large populations. Generally speaking, recurrence risks are an average that will vary from family to family. The risk is dependent upon several factors. These include the degree of relatedness, the number of affected individuals in a family, the sex of the affected individual, and the severity of the disease.

  The degree of relatedness is important in determining risk to future pregnancies. For many multifactorial disorders, parents who have had one affected child have a 3-5% risk in future pregnancies of having another affected child. Affected individuals have a similar risk in their future progeny. More distant relatives, however, have a lower recurrence risk. For example, an individual who has cleft lip and palate would be at higher risk of having a child with the same condition than an individual who has a brother or sister with the condition who is not affected themselves.

  The number of affected individuals in a family is also important in determining risk. For example, if a couple has two children with a multifactorial condition such as a congenital heart defect (CHD), their subsequent children would be at greater risk than if the couple only had one child with a CHD.

  The sex of the affected individual in an important factor in determining risk of recurrence when there is a difference in the ratio of affected males to affected females in the general population. For example, pyloric stenosis is a multifactorial disorder that occurs five times more frequently in males than in females. If a female child has pyloric stenosis, her risk and her parent's risk of having another affected child would be higher than if a male child has pyloric stenosis. Occurrence in a female suggests a greater genetic liability; presumably more abnormal genes are segregating in the family. In addition, the degree of severity is important, too. If a baby is born with bilateral (meaning both sides) cleft lip, for example, his or her future brothers and sisters would be at higher risk that if the cleft lip was unilateral (or only on one side).

• Prevention of Multifactorial Diseases - At this point in time, there is no way to prevent a multifactorial disease from occurring in a newborn. However, in the last decade, there have been great advancements made in the area of neural tube defects (NTDs). There is substantial evidence that the vitamin folic acid reduces the incidence of neural tube defects such as spina bifida. (Go to Spina Bifida to learn more.)

 

Mitochondrial Inheritance

There is another group of genetic diseases that are inherited in yet a different method. When we refer to DNA we are usually referring to the DNA that is found in the nucleus of our cells, which is organized as chromosomes. However, there is another kind of DNA that is found exclusively in organelles outside of the cell nucleus, called the mitochondria. Mitochondria are important because they provide much of the energy that is needed by cells to function properly. Mitochondria containe DNA separate from the DNA that is a part of our chromosomes. This DNA is inherited in a different pattern.

• Types of Diseases Caused by Mutations in Mitochondrial DNA - There are several human diseases that are usually caused by mutations, or changes, in the mitochondrial DNA. Most of these diseases affect the nervous system, heart or skeletal muscles, liver, or kidneys. Depending on what cells in the body are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection.

• Inheritance of Mitochondrial Disorders - Mitochondrial disorders are generally passed from an affected mother to 100% of her children. This is because mitochondria are located in maternal egg cells. The mitochondria present in sperm are concentrated in the tail and do not contribute to the compliment of the fertilized zygote. Hence, a male with a mitochondrial disease is not at risk to have children affected with the disease.

  Mitochondrial disorders may seem easy to identify in a family based upon the fact that 100% of individuals from an affected mother are affected themselves. It is not so easy, however, since variability is the norm for these types of disorders. For example, there may be a family where some individuals present with strokes, others with muscle weakness, and others with only an ophthalmological problem.