Mitochondrial Genetic Disorders: Monogenic Disease

A monogenic disease is a condition determined by the interaction of a single pair of genes. Compared to the other, polygenic condition wherein several genes (polygene) are involved. The monogenic disease is less common than the polygenic disease. It is also less complicated than the latter and may follow a pattern based on Mendelian inheritance.

They are inherited according to Mendel’s Laws (Mendelian disorders). The mutation can be spontaneous and where there is no previous family history. Inheritance patterns can be autosomal dominant, autosomal recessive or X-linked recessive. Over 10,000 human disorders are caused by a change, known as a mutation, in a single gene. Since monogenic disease involves a single pair of genes the dysfunctional or mutated gene may be identified more easily than polygenic disease.

In monogenic disease, a single gene mutation may lead to disease. Monogenic diseases are mostly pediatric disorders. So, it can be mainly seen in children. Some of human diseases due to autosomal dominant single-gene defects include polycystic kidney disease, neurofibromatosis type I, familial hypercholesterolemia, hereditary spherocytosis, Marfan syndrome, and Huntington’s disease.

Examples of autosomal recessive monogenic disorders include sickle cell anaemia, cystic fibrosis, Tay-Sachs disease, phenylketonuria, mucopolysaccharidoses, glycogen storage diseases, and galactosemia. X-linked monogenic disorders are single-gene mutations in the X chromosome. They include hemophilia and Duchenne muscular dystrophy. Y-linked monogenic disorders are associated with single-gene mutations in the Y chromosome and are very rare. These are passed on from father to their sons. Mitochondrial disease is another example of a monogenic disorder and involving mitochondrial DNA, which is passed from the mother to offspring.

Autosomal dominant is one of several ways that a trait or disorder can be passed down (inherited) through families. In an autosomal dominant disease, if you inherit the abnormal gene from only one parent, you can get the disease. Often, one of the parents may also have the disease. Inheriting a disease, condition, or trait depends on the type of chromosome affected (nonsex or sex chromosome). It also depends on whether the trait is dominant or recessive.

A single abnormal gene on one of the first 22 nonsex (autosomal) chromosomes from either parent can cause an autosomal disorder. Dominant inheritance means an abnormal gene from one parent can cause disease. This happens even when the matching gene from the other parent is normal. The abnormal gene dominates.

This disease can also occur as a new condition in a child when neither parent has the abnormal gene.A parent with an autosomal dominant condition has a 50% chance of having a child with the condition. This is true for each pregnancy. It means that each child’s risk for the disease does not depend on whether their sibling has the disease. Children who do not inherit the abnormal gene will not develop or pass on the disease. If someone is diagnosed with an autosomal dominant disease, their parents should also be tested for the abnormal gene. Examples of autosomal dominant disorders include Huntington disease and neurofibromatosis type 1.

Some health problems are passed down through families. There are different ways this can happen. To have a child born with what’s called an “autosomal recessive disease” like sickle cell disease or cystic fibrosis, both you and your partner must have a mutated (changed) gene that you pass on to your child. Almost every cell in your body contains 23 pairs of tightly wound DNA called chromosomes. You get 23 of them from your mother and 23 from your father.

One pair of chromosomes decides your sex. The others contain thousands of different genes that decide every other trait you have, from hair and eye color to your risk of getting diseases. These are called autosomes.

Some genes are “dominant.” You only need one from a parent to have that trait. Other genes are “recessive.” With them, you have to inherit the same gene from both parents to be affected. If one of your parents passes on a recessive gene to you that can cause disease, then you become a “carrier.” You likely won’t have any symptoms, since the other gene is normal. In fact, many people won’t know they’re a carrier without being tested.

Mitochondrial genetic disorders refer to a group of conditions that affect the mitochondria. Because only egg cells contribute mitochondria to the developing embryo, only mothers can pass on mitochondrial DNA conditions to their children. People with these conditions can present at any age with almost any affected body system; however, the brain, muscles, heart, liver, nerves, eyes, ears and kidneys are the organs and tissues most commonly affected. When the mitochondria are not working properly, the body does not have enough energy to carry out its normal functions. This can lead to the variety of health problems associated with mitochondrial genetic disorders.

Sex-linked diseases are passed down through families through one of the X or Y chromosomes. X and Y are sex chromosomes. Dominant inheritance occurs when an abnormal gene from one parent causes disease even though the matching gene from the other parent is normal. The abnormal gene dominates.

But in recessive inheritance, both matching genes must be abnormal to cause disease. If only one gene in the pair is abnormal, the disease does not occur or it is mild. Someone who has one abnormal gene (but no symptoms) is called a carrier. Carriers can pass abnormal genes to their children.

The term “sex-linked recessive” most often refers to X-linked recessive. X-linked recessive diseases most often occur in males. Males have only one X chromosome. A single recessive gene on that X chromosome will cause the disease.

The Y chromosome is the other half of the XY gene pair in the male. However, the Y chromosome doesn’t contain most of the genes of the X chromosome. Because of that, it doesn’t protect the male. Diseases such as hemophilia and Duchenne muscular dystrophy occur from a recessive gene on the X chromosome.