Using Karyotypes To Diagnose Genetic Disorders
A regular human cell has 46 chromosomes: 44 autosomes, which come in pairs, and 2 sex chromosomes, which specify gender (XX for female and XY for male).
The pairs of autosomes are called "homologous chromosomes." One of each pair came from mom and the other came from dad. Homologous chromosomes have all of the same genes arranged in the same order, but with slight differences in the DNA sequences of the genes.
What happens when a person has something different, such as too many or too few chromosomes, missing pieces of chromosomes, or mixed up pieces of chromosomes?
Before we look at how the process can go wrong, let's take a look at how cells normally get 46 chromosomes.
Egg and sperm cells have just 23 chromosomes each. That's half as many chromosomes as regular cells. Through the process of fertilization, egg and sperm join to make a cell with 46 chromosomes, called a zygote.
Before the zygote divides to make two cells, it copies each chromosome. These copies, called sister chromatids, are identical. When the zygote divides, each cell gets one identical copy of each chromosome. The cells continue dividing this way to make a person. This type of cell division is called mitosis.
When egg and sperm form, they go through a special type of cell division called meiosis. One purpose of meiosis is to reduce the number of chromosomes by half. The other is to create genetic diversity.
Meiosis begins like mitosis: the cell copies each chromosome. But unlike in mitosis, homologous chromosome pairs line up and exchange pieces—a process called recombination. Remember, homologous chromosomes have the same genes but with slight differences. Recombination increases genetic diversity by putting pieces of chromosomes that came from mom together with pieces of chromosomes that came from dad.
Next, the newly recombined homologous chromosomes are divided into two daughter cells. Then the sister chromatids are pulled apart into a total of four cells. Each of these cells has one copy each of 23 chromosomes, all with a unique combination of mom's and dad's genes.
Too Many or Too Few Chromosomes
Sometimes chromosomes are incorrectly distributed into the egg or sperm cells during meiosis. When this happens, one cell may get two copies of a chromosome, while another cell gets none. If a sperm or egg cell with too many or too few chromosomes participates in fertilization, it will produce a zygote with too many or too few chromosomes.
Incorrect distribution of chromosomes is called nondisjunction. A zygote with 3 copies of a chromosome is said to have trisomy (pronounced TRY-so-mi). A zygote that is missing a chromosome is said to have monosomy (MOH-no-so-mi).
Most of the time, autosomal (non-sex chromosome) trisomy and monosomy are lethal because the zygote ends up with too much or too little genetic information. But sometimes, babies are born with extra or missing autosomes—most commonly one of the smaller chromosomes that have fewer genes. Usually these babies have a genetic disorder, which scientists can diagnose by looking for extra or missing chromosomes in a karyotype.
When monosomy or trisomy involves sex chromosomes, individuals usually survive and many are quite healthy.
Sometimes pieces of chromosomes are lost or rearranged during meiosis. This happens during the recombination step, when maternal and paternal chromosomes swap pieces.
When genetic material is missing, a chromosome is said to have a deletion. Deletions of the tips of chromosomes are called terminal deletions. Internal deletions, where a chromosome has broken, lost material, and rejoined, are called interstitial (in-ter-STIH-shul) deletions.
Chromosomes with deletions large enough to be visible on a karyotype are missing many genes. In humans, such large deletions are less common than smaller deletions, which often cannot be seen on a karyotype. As with too many or too few chromosomes, deletions can cause genetic disorders. The symptoms of deletion disorders vary, depending on which genes are missing.
A translocation is a chromosome rearrangement in which part of a chromosome breaks off and then reattaches to a non-homologous chromosome. Types of translocations include reciprocal and Robertsonian.
A reciprocal translocation is a swap between two chromosomes. In a balanced translocation, the individual has all of their genes, and they are typically healthy. A translocation where genes are also duplicated or deleted is called an unbalanced translocation. Individuals with extra or missing genetic material usually have a genetic disorder.
A Robertsonian translocation occurs when the long arms of two acrocentric chromosomes fuse at a centromere. The two short arms are lost, leaving a total of 45 chromosomes. But because the short arms carry very little genetic information, individuals with Robertsonian translocations are usually healthy.