In this explainer, we will learn how to identify chromosomal abnormalities from a karyotype and explain the effects of these abnormalities.
Chromosomal abnormalities affect about 1 in every 150 babies, and each child born with a chromosomal abnormality is different. Some chromosomal abnormalities have very little impact on development, while others can cause serious problems. The effect of chromosomal abnormalities depends on which chromosomes are changed and how.
The human body typically has 46 chromosomes in each cell that are grouped into 23 pairs. Chromosome pairs 1 through 22 are called autosomes, while the 23rd chromosome pair is called sex chromosomes. Unlike autosomes, which are the same in male and female cells, sex chromosomes are different in male and female cells. Sex chromosomes come in two types, X and Y, and help in sex determination of humans.
Male cells have an XY sex chromosome pair, while female cells have an XX sex chromosome pair. Our chromosomes are passed down to us from our biological parents, one set from our biological mother and one from our biological father, through gametes (sex cells). Figure 1 demonstrates how a zygote (fertilized egg cell) inherits chromosomes from its biological parents.
A chromosome is a long molecule of DNA and associated proteins that contains the genetic information of an organism in the form of genes.
Definition: Sex Chromosome
A sex chromosome is a chromosome that helps to determine sex in humans and can be one of two types, X or Y.
Gametes are formed through the process of meiosis, which is a special form of cell division that helps divide genetic information evenly between two sex cells. At the end of meiosis, the gametes have half the full number of chromosomes (22 autosomes and 1 sex chromosome) found in a somatic cell (44 autosomes and 2 sex chromosome).
Gametes or sex cells are created through a special type of somatic cell division called meiosis. The process of meiosis is how somatic cells that are diploid (2n) become haploid (n). This means that after meiosis, the number of chromosomes in a cell is 23 instead of 46. The 23 chromosomes are one set of autosomes and one sex chromosome (X or Y). In humans, meiosis occurs in the reproductive organs to make the female sex cells, called ova, and the male sex cells, called sperm.
In order to examine an individual’s chromosomes, a karyotype is used. A karyotype is a picture of an individual’s chromosomes in which the chromosomes have been classified into their homologous pairs and ordered by size order from largest to smallest, where chromosome 1 is the largest pair of chromosomes.
A karyotype is a visual display of all the chromosomes in a cell, arranged in homologous pairs and in decreasing-size order.
If meiosis does not go according to plan, sex cells can end up carrying a chromosomal abnormality. A chromosomal abnormality is a change in the expected structure or number of an individual’s chromosome. Chromosomal abnormalities are a big concern if the chromosomal abnormalities are expected to cause a change in development and future health of the fetus.
Definition: Chromosomal Abnormality
A chromosomal abnormality is a change in the expected structure or number of an individual’s chromosomes.
Chromosomal abnormalities can be categorized as changes in structure or number (loss or gain) of chromosomes. Depending on the chromosomal abnormality, a different set of health traits can be observed by a medical doctor.
The most common chromosomal abnormalities are related to changes in the number of chromosomes. A change in the number of chromosomes can mean an increase in the number of chromosomes, so going from an expected 46 chromosomes to 47 or more. A shorthand for expressing a gamete containing an extra chromosome is . The “n” represents the expected number of chromosomes in a gamete, typically 23, and the “” indicates the presence of one extra chromosome. If this gamete were to fuse with another gamete that possesses the typical number of chromosomes, the zygote would possess 47 instead of the typical 46 chromosomes. Figure 2 below demonstrates the inheritance of an additional chromosome.
The most common examples of a chromosomal abnormality created by a change in the number of chromosomes is Down syndrome. The Victorian physician Dr. John Langdon Down is attributed with first identifying the traits of Down syndrome in a group of patients. In Down syndrome, instead of the expected two homologous chromosomes 21, there are three chromosomes. This means that people with Down syndrome have a total of 47 chromosomes made up of 45 autosomes, instead of the expected 44 autosomes, and 2 sex chromosomes, either XX or XY.
Key Term: Down Syndrome
Down syndrome is a set of traits caused by an extra chromosome 21.
Figure 3 shows a karyotype of a Down syndrome patient. You can see that for chromosomes 1 to 20 there are 2 chromosomes, but for chromosome 21, there are 3 chromosomes. The extra chromosome in Down syndrome disrupts the typical course of development and results in several physical and mental traits associated with the syndrome.
The word syndrome is used because, while every person that has an extra autosome in chromosome 21 has the same traits, the presentation of these traits can vary from person to person. For example, while many people who have Down syndrome have characteristic traits, like a flattened facial appearance and delayed mental development, the way these traits are expressed can be different from person to person. So, the word syndrome is used to describe a set of traits related to a certain condition.
A syndrome is a set of traits that occur together and indicate the presence of a certain condition.
The most common traits of someone with Down syndrome include delays in developing language in childhood, heart defects, low muscle tone, flattened facial profile with upward slanting eyes, being shorter in height than individuals of the same age that do not have Down syndrome, and having shorter, broader hands. They may have a single, deep crease across the palm of the hand and a widely separated first and second toes, as shown in Figure 4 below.
People with Down syndrome can also experience a variety of mental traits, like delayed development and problems with thinking and learning. Severity of these mental traits usually ranges from mild to moderate. With early intervention and the appropriate support, most adults with Down syndrome are able to have a high quality of life, find gainful employment, and live independently.
Example 1: Describing How to Use A Karyotype to Identify Down Syndrome
A karyotype is an image of a person’s chromosomes that can be used to determine chromosomal abnormalities.
Which syndrome will likely be developed as a result of the chromosomal abnormality shown in the karyotype provided?
- Down syndrome
- Turner syndrome
- Klinefelter syndrome
Karyotyping is a test to identify and evaluate the size, shape, and number of chromosomes in an individual’s somatic cells. In a human with no chromosomal abnormalities, a karyotype will show 46 chromosomes that are grouped as 22 matching pairs and 1 pair of sex chromosomes, either XX for females or XY for males. In the karyotype, the homologous pairs of chromosomes will be placed together. The chromosome pairs will also be arranged in descending-size order so that chromosome 1, which is the largest, is first and chromosome 22, which is the smallest, is last. A chromosomal abnormality is identified if the karyotype shows any extra or missing chromosomes as well as any structural changes to the chromosomes.
In this karyotype, we see a set of three chromosomes above the number 21. Down syndrome is caused by an extra autosome in chromosome 21, so the three autosomes counted in chromosome 21 are a classic indication of Down syndrome.
Therefore, the syndrome likely to be caused by the chromosomal abnormality shown in the karyotype provided is Down syndrome.
Down syndrome is caused by a change in the number of autosomes, the chromosomes that are the same in male and female cells. However, chromosomal abnormalities can also happen in the sex chromosomes, which are not the same between male and female cells. Let’s discuss what happens when a chromosomal abnormality changes the number of sex chromosomes in the zygote, as seen in Figure 5.
The most well-known example of syndrome resulting from an extra sex chromosome is Klinefelter syndrome. Klinefelter syndrome is named after Dr. Harry Klinefelter, who is credited with first describing the traits of this syndrome he observed in a group of men. Klinefelter syndrome is caused by the presence of an extra X chromosome in males, changing their sex chromosomes from the typical XY to XXY. In the karyotype below in Figure 6, you can see that for chromosomes 1 to 22, there are 2 chromosomes, but for chromosome 23, there are three chromosomes, two Xs and one Y. Since the only chromosomal abnormality in this karyotype is an extra X chromosome, the doctor will be able to diagnose the individual with Klinefelter syndrome.
Key Term: Klinefelter Syndrome
Klinefelter syndrome is a set of traits in males caused by an extra X chromosome (an XXY male).
The most well-known traits of Klinefelter syndrome include a taller-than-average height, infertility, reduced development of facial hair, and the development of breasts. These traits are summarized in Figure 7. Males with Klinefelter syndrome also have less of the male sex hormone, testosterone, which leads to delayed puberty and infertility. Infertility in males means that they have difficulty in generating healthy sperm, which are necessary to cause pregnancy.
Example 2: Examining A Karyotype to Identify Klinefelter Syndrome
Karyotypes are images of a person’s chromosomes that can be used to determine chromosomal abnormalities.
Which syndrome is likely to be caused by the chromosomal abnormality shown in the karyotype provided?
- Klinefelter syndrome
- Turner syndrome
- Down syndrome
Karyotyping is a test to identify and evaluate the size, shape, and number of chromosomes in an individual’s somatic cells. In a human with no chromosomal abnormalities, a karyotype will show 46 chromosomes that are grouped as 22 matching pairs and 1 pair of sex chromosomes, either XX for females or XY for males. Each chromosome will have one homologous chromosome to make a pair. The chromosome pairs will also be arranged in descending-size order so that chromosome 1, which is the largest, is first and chromosome 22, which is the smallest, is last. A chromosomal abnormality is identified if the karyotype shows any extra or missing chromosomes as well as any structural changes to the chromosomes.
In the last pair, there are three sex chromosomes, meaning there is an extra X chromosome. Both Down syndrome and Klinefelter syndrome are caused by an extra chromosome. However, Down syndrome is caused by an extra autosome in chromosome 21, while Klinefelter syndrome is caused by an extra X chromosome. In the karyotype, we see that chromosome 21 only has two autosomes.
Therefore, the syndrome likely to be caused by the chromosomal abnormality shown in the karyotype provided is Klinefelter syndrome.
Even though there is an extra X chromosome in Klinefelter syndrome, that does not mean the biological sex of the individual is female. Presence of the Y chromosome (and the SRY gene) in Klinefelter syndrome mean that individuals will develop the reproductive organs found in XY males and the external and internal structures associated with it. Klinefelter syndrome occurs in about 1 out of every 500–1 000 newborn males.
In Klinefelter syndrome, the extra X chromosomes can come from either the biological mother through the ova that is XX instead of X or from the biological father through a sperm that is XY instead of X or Y. The end result, no matter which gamete has the extra X, is a zygote with the 47 chromosomes, 44 autosomes and 3 sex chromosomes (XXY). Interestingly, because the traits of Klinefelter syndrome can be mild, many males with Klinefelter syndrome are never diagnosed and have a high quality of life.
Finally, a change in the number of chromosomes in the zygote can also describe the loss of a sex chromosome. A loss of a chromosome means going from an expected 46 chromosomes to 45 or less. A shorthand for expressing a gamete that contains one less than the expected number of chromosomes is . The “n” represents the expected set of chromosomes in a gamete, typically 23, and the “” indicates the absence of one chromosome, as shown in Figure 8.
The most well-known example of a syndrome that results from a loss in sex chromosome is Turner syndrome. In Turner syndrome, instead of the expected two sex chromosomes, there is only one X chromosome. This means that a zygote Turner syndrome will have a total of 45 chromosomes, 44 autosomes and 1 sex chromosome, XO. In typical female cells, there are two X chromosomes, which is noted by the presence of two XX chromosomes, but for Turner syndrome where there is a missing X chromosome, the “O” is used as a substitute for the missing chromosome.
Key Term: Turner Syndrome
Turner syndrome is a set of traits in females caused by the loss of an X chromosome (an XO female).
In Figure 9 below, you can see that for chromosomes 1 to 22, there are 2 chromosomes, but for chromosome 23, there is only 1 chromosome. With the only chromosomal abnormality in this karyotype being a missing X chromosome in chromosome 23, the doctor will be able to diagnose the individual with Turner syndrome.
The most well-known traits of Turner syndrome include a webbed neck, presence of congenital defects in the heart and kidneys, loss of ovary function, infertility, and stunted height. Most of the traits associated with Turner syndrome are related to the missing X chromosome, which leads to lower expression of female hormones, like estrogen, and the underdevelopment of the ovaries. Those with Turner syndrome may not be able to progress through puberty without the help of hormone replacements. While most individuals with Turner syndrome do not have issues with learning and memory, there are some individuals who experience developmental and learning disabilities. The most challenging physical and mental traits of Turner syndrome can be treated with hormone therapy and educational supports, so females with Turner syndrome can have a high quality of life.
Turner syndrome is only observed in females and occurs in about 1 out of every 2 500 female births. Turner syndrome is also the only chromosomal abnormality where the loss of a chromosome is tolerated. Any other time a chromosome is lost or absent in a zygote, the zygote is unable to develop into a fetus and be born.
Example 3: Defining How A Chromosomal Abnormality Is Caused
The passage provided outlines how chromosomal abnormalities can be caused.
Chromosomal abnormalities can be caused by changes in the of chromosomes, or a complete loss or of entire chromosomes.
Which word would be most appropriate to replace the first blank?
Which word would be most appropriate to replace the second blank?
A human somatic cell contains 46 chromosomes, the threadlike structures that contain all of our genetic information in the form of DNA. The 46 chromosomes are grouped into 23 pairs, 22 pairs of autosomes and 1 pair of sex chromosomes. Autosomes are similar between male and female cells. The pair of sex chromosomes help determine the sex of the offspring and are different in male and female cells. Male cells, called sperm, have an X and Y sex chromosome, while female cells, called ova, have 2 X chromosomes. In reproduction, new cells called gametes are formed to pass down our genetic information to our offspring. Gametes contain half the number of autosomes found in somatic cells (22) and one of the sex chromosomes. In reproduction, after the sperm and ova fuse, the zygote then has one set of 22 autosomes and 1 sex chromosome, from each biological parent, which equals 46 chromosomes.
When the zygote does not have the expected 46 chromosomes, then it is most possible that a chromosomal abnormality has occurred. A chromosomal abnormality causes a change in the expected structure or number of chromosomes. The most common chromosomal abnormalities are a change in the number of chromosomes, which can mean either the addition of an extra chromosome or the loss of an entire chromosome.
Therefore, chromosomal abnormalities can be caused by changes in the structure of chromosomes, or a complete loss or gain of entire chromosomes.
Let’s summarize some key points we have learned.
- A chromosomal abnormality causes a change in the expected structure or number of chromosomes.
- Down syndrome is chromosomal abnormality caused by an extra autosome in chromosome 21.
- Klinefelter syndrome is chromosomal abnormality caused by an extra X sex chromosome.
- Turner syndrome is chromosomal abnormality caused by the loss of one X sex chromosome.
- A karyotype is a picture of an individual’s chromosomes grouped into homologous pairs and arranged in descending-size order. A karyotype can be used to detect chromosomal abnormalities by visually inspecting the picture for any changes in the structure, size, or number of the expected 44 autosomes and 2 sex chromosomes.