Figure 1. Each hand in this photo has an extra pinky finger. This is a condition called polydactyly, which literally means "many digits." People with polydactyly may have extra fingers and/or toes, and the condition may affect just one hand or foot or both hands and feet. Polydactyly is often genetic in origin and may be part of a genetic disorder that is associated with other abnormalities.
What Are Genetic Disorders?
Genetic disorders are diseases, syndromes, or other abnormal conditions that are caused by mutations in one or more genes or by chromosomal alterations. Genetic disorders are typically present at birth, but they should not be confused with congenital disorders, which are any disorders, regardless of cause, that are present at birth. Some congenital disorders are not caused by genetic mutations or chromosomal alterations. Instead, they are caused by problems that arise during embryonic or fetal development or during the process of birth. An example of a nongenetic congenital disorder is fetal alcohol syndrome. This is a collection of birth defects, including facial anomalies and intellectual disability, caused by maternal alcohol consumption during pregnancy.
Genetic Disorders Caused by Mutations
The table below lists several genetic disorders caused by mutations in just one gene. Some of the disorders are caused by mutations in autosomal genes, others by mutations in X-linked genes. Which disorders would you expect to be more common in males than females?
|Genetic Disorder||Direct Effect of Mutation||Signs and Symptoms of the Disorder||Mode of Inheritance|
|Marfan syndrome||defective protein in connective tissue||heart and bone defects and unusually long, slender limbs and fingers||autosomal dominant|
|Sickle cell anemia||abnormal hemoglobin protein in red blood cells||sickle-shaped red blood cells that clog tiny blood vessels, causing pain and damaging organs and joints||autosomal recessive|
|Vitamin D-resistant rickets||lack of a substance needed for bones to absorb minerals||soft bones that easily become deformed, leading to bowed legs and other skeletal deformities||X-linked dominant|
|Hemophilia A||reduced activity of a protein needed for blood clotting||internal and external bleeding that occurs easily and is difficult to control||X-linked recessive|
Very few genetic disorders are controlled by dominant mutant alleles. A dominant allele is expressed in every individual who inherits even one copy of it. If it causes a serious disorder, affected people may die young and fail to reproduce. Therefore, the mutant dominant allele is likely to die out of the population.
A recessive mutant allele, such as the allele that causes sickle cell anemia or cystic fibrosis, is not expressed in people who inherit just one copy of it. These people are called carriers. They do not have the disorder themselves, but they carry the mutant allele and their offspring can inherit it. Thus, the allele is likely to pass on to the next generation rather than die out.
Genetic Disorders Caused by Chromosomal Alterations
As we learned in the Cell Reproduction chapter, mistakes may occur during meiosis that result in nondisjunction. This is the failure of replicated chromosomes to separate properly during meiosis. Some of the resulting gametes will be missing all or part of a chromosome, while others will have an extra copy of all or part of the chromosome. If such gametes are fertilized and form zygotes, they usually do not survive. If they do survive, the individuals are likely to have serious genetic disorders.
The table below lists several genetic disorders that are caused by abnormal numbers of chromosomes. Most chromosomal disorders involve the X chromosome. The X and Y chromosomes are the only chromosome pair in which the two chromosomes are very different in size. This explains why nondisjunction of the sex chromosomes tends to occur more frequently than nondisjunction of autosomes.
|Genetic Disorder||Genotype||Phenotypic Effects|
|Down syndrome||extra copy (complete or partial) of chromosome 21 (see figure below)||developmental delays, distinctive facial appearance, and other abnormalities (see figure below)|
|Turner’s syndrome||one X chromosome but no other sex chromosome (XO)||female with short height and infertility (inability to reproduce)|
|Triple X syndrome||three X chromosomes (XXX)||female with mild developmental delays and menstrual irregularities|
|Klinefelter’s syndrome||one Y chromosome and two or more X chromosomes (XXY, XXXY)||male with problems in sexual development and reduced levels of the male hormone testosterone|
Figure 2. Trisomy 21 (Down Syndrome) Karyotype. A karyotype is a picture of a cell's chromosomes. Note the extra chromosome 21. Child with Down syndrome, exhibiting characteristic facial appearance.
Diagnosing and Treating Genetic Disorders
A genetic disorder that is caused by a mutation can be inherited. Therefore, people with a genetic disorder in their family may be concerned about having children with the disorder. A genetic counselor can help them understand the risks of their children being affected. If they decide to have children, they may be advised to have prenatal (“before birth”) testing to see if the fetus has any genetic abnormalities. One method of prenatal testing is amniocentesis. In this procedure, a few fetal cells are extracted from the fluid surrounding the fetus in utero, and the fetal chromosomes are examined. Down syndrome and other chromosomal alterations can be detected in this way.
The symptoms of genetic disorders can sometimes be treated or prevented. For example, in the genetic disorder called phenylketonuria (PKU), the amino acid phenylalanine builds up in the body to harmful levels. PKU is caused by a mutation in a gene that normally codes for an enzyme needed to break down phenylalanine. When a person with PKU consumes foods high in phenylalanine (which includes many high-protein foods), the buildup of PKU can lead to serious health problems. In infants and young children, the buildup of phenylalanine can cause intellectual disability and delayed development, among other serious problems. Babies in the United States and many other countries are screened for PKU soon after birth. If PKU is diagnosed, the infant can be fed a low-phenylalanine diet. This prevents the buildup of phenylalanine and the health problems associated with it, including intellectual disability. As long as a low-phenylalanine diet is followed throughout life, most symptoms of the disorder can be prevented.
Curing Genetic Disorders
Cures for genetic disorders are still in the early stages of development. One potential cure is gene therapy. Gene therapy is an experimental technique that uses genes to treat or prevent disease. In gene therapy, normal genes are introduced into cells to compensate for abnormal genes. If a mutated gene causes a necessary protein to be nonfunctional or missing, gene therapy may be able to introduce a normal copy of the gene to produce the needed functional protein.
A gene that is inserted directly into a cell usually does not function, so a carrier called a vector is genetically engineered to deliver the gene (see illustration below). Certain viruses, such as adenoviruses, are often used as vectors. They can deliver the new gene by infecting cells. The viruses are modified so they do not cause disease when used in people. If the treatment is successful, the new gene delivered by the vector will allow the synthesis of a functioning protein. Researchers still must overcome many technical challenges before gene therapy will be a practical approach to curing genetic disorders.
Figure 3.Gene therapy is an experimental technique for curing a genetic disorder by changing the patient's genetic makeup. Typically, gene therapy involves introducing a normal copy of a mutant gene into the patient's cells.
Feature: Human Biology in the News
Down syndrome is the most common genetic cause of intellectual disability. It occurs in about 1 in every 700 live births, and it currently affects nearly half a million Americans. Until recently, scientists thought that the changes leading to intellectual disability in people with Down syndrome all happen before birth.
Researchers recently discovered a genetic abnormality that affects brain development in people with Down Syndrome throughout childhood and into adulthood. The newly discovered genetic abnormality changes communication between nerve cells in the brain, resulting in slower transmission of nerve impulses. This finding may eventually allow the development of strategies to promote brain functioning in Down syndrome patients and may also be applicable to other development disabilities such as autism. The results of this promising study were published in the March 16, 2016 issue of the scientific journal Neuron.
- Genetic disorders are diseases, syndromes, or other abnormal conditions that are caused by mutations in one or more genes or by chromosomal alterations.
- Examples of genetic disorders caused by single-gene mutations include Marfan syndrome (autosomal dominant), sickle cell anemia (autosomal recessive), vitamin D-resistant rickets (X-linked dominant), and hemophilia A (X-linked recessive). Very few genetic disorders are caused by dominant mutations because these alleles are less likely to be passed on to successive generations.
- Nondisjunction is the failure of replicated chromosomes to separate properly during meiosis. This may result in genetic disorders caused by abnormal numbers of chromosomes. An example is Down syndrome, in which the individual inherits an extra copy of chromosome 21. Most chromosomal disorders involve the X chromosome. An example is Klinefelter's syndrome (XXY, XXXY).
- Prenatal genetic testing, for example, by amniocentesis, can detect chromosomal alterations in utero. The symptoms of some genetic disorders can be treated or prevented. For example, symptoms of phenylketonuria (PKU) can be prevented by following a low-phenylalanine diet throughout life.
- Cures for genetic disorders are still in the early stages of development. One potential cure is gene therapy, in which normal genes are introduced into cells by a vector such as a virus to compensate for mutated genes.
- Define genetic disorder.
- Identify three genetic disorders caused by mutations in a single gene.
- Why are single-gene genetic disorders more commonly controlled by recessive than dominant mutant alleles?
- What is nondisjunction? Why may it cause genetic disorders?
- Explain why genetic disorders caused by abnormal numbers of chromosomes most often involve the X chromosome.
- How is Down syndrome detected in utero?
- Use the example of PKU to illustrate how the symptoms of a genetic disorder can sometimes be prevented.
- Explain how gene therapy works.
- Compare and contrast genetic disorders and congenital disorders.
- Explain why parents that do not have Down syndrome can have a child with Down syndrome.
- Hemophilia A and Turner’s syndrome both involve problems with the X chromosome. What is the major difference between these two types of disorders in terms of how the X chromosome is affected?
- Can you be a carrier of Marfan syndrome and not have the disorder? Explain your answer.
- True or False. It is impossible for people to have more than three copies of one chromosome.
- True or False. The gene for sickle cell anemia is on a sex chromosome.
Scientists have promised that gene therapy will be the next big leap for medicine, but what is it exactly? Learn more here:
Imagine if we could fix a patient's own cells and cure their genetic disease once and for all instead of treating their chronic illness slowly over time. Learn more about gene therapy here:
Credit: By Baujat G, Le Merrer M. [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons;
License: CC BY-NC 3.0
Credit: By Courtesy: National Human Genome Research Institute (Human Genome Project) [Public domain], via Wikimedia Commons;
Credit: By Darryl Leja, NHGRI [Public domain], via Wikimedia Commons;
License: CC BY-NC 3.0