Introduction
A genetic disorder is an illness that is caused due to a change in an individual’s DNA. The change can occur if there was an error that occurred while the DNA was being replicated in the S phase of Interphase. It can also be caused by environmental factors that the individual was commonly exposed to like smoking and extreme exposure to radiation. In simple terms, every individual has a human genome. This has a complete set of encoded DNA that lies within the 23 pairs of chromosomes within the nucleus. Each chromosome contains a large abundance of genes which ultimately has the formula for making proteins, which are crucial to perform most of the functions in our body. When a change occurs in our DNA, the proteins that it codes for are also affected. Depending on where the mutation occurred, this can have a drastic or minimal effect to the biology of the cells in our body. It’s from that effect that a genetic disorder results from.
Genetic disorders can be divided into several categories. Throughout this research paper, the categories that will be discussed include chromosomal, gene and x-linked disorders. Out of thousands of known genetic disorders, the chromosomal disorder that this paper is going to be focused on is the Swyer syndrome, the genetic disorder of Huntington and the x-linked disorder, Kennedy’s disease. The common factor between all of these is that they are more commonly found in men than in women.
SWYER SYNDROME
Swyer syndrome is a disease that affects sexual development. It occurs in about 1 in 80,000 people. While sexual development is supposed to match our chromosomes (XX or XY) depending on our gender, this disease makes it so that the chromosomal makeup of the affected individual doesn’t match with their sexual development. In Swyer syndrome, although males have an X and Y chromosome, they have female reproductive systems. While they have a uterus and fallopian tubes, their gonads which are the ovaries and testes are not functional. The individuals with Swyer syndrome have undeveloped tissue called streak gonads which in most cases has proven to be cancerous therefore affected individuals prefer to surgically remove the tissue early on their lives. People that have the disease are usually raised as women and identify themselves as women.
Inheritance
In most cases the syndrome is not inherited, meaning that the individual may not have a history of this syndrome in their family. These cases occur in the early development of the fetus in which mutations occur. There are several causes that may lead to Swyer syndrome. Approximately 15% of individuals with Swyer syndrome have been connected to having a mutation in the SRY gene. The SRY gene is located in the Y chromosome and the mutation prevents the sex-determining region Y protein to be produced correctly or it produces it as a nonfunctioning protein. Due to this, the nonfunctioning protein will prevent the fetus from developing the testes and instead will lead to the development of a uterus and fallopian tubes.
Genetic changes
About 18% of cases attribute the Swyer syndrome to a mutation in the MAP3K1 gene which is responsible for providing the instructions that contribute to providing the pathways that control different processes that occur in the body. One of these pathways involves determines the sexual characteristics of the fetus before the baby is born. The mutations in this gene result in decreased signaling of the characteristics that leads to a male development and increases the signaling that results in female development.
Another mutation that has been found in Swyer syndrome cases involves the DHH and NR5A1 genes. While the DHH gene provides a manual for producing a protein that is crucial in the early development of the tissues in the body, the NR5A1 gene provides a manual for producing the SF1 steroidogenic factor, which helps maintain the activity of genes that are related to the production of sex hormones.
Treatment
For this diseases there are several treatment options. The treatments options available depend on the the characteristics that the individual has. For example, some people need to go through surgery in order to fix their genitalia in order to either create or expand the vagina. A more common treatment involves Hormone replacement therapy from a very early on age which helps develop the individual’s sexual characteristics and helps prevent bone loss and thinning known as osteoporosis later on in life. Women that suffer from Swyer syndrome are infertile however they can become pregnant through a process of egg donation.
HUNTINGTON DISEASE
The gene disorder, Huntington’s disease is an inherited disease which causes uncontrollable movements, intense emotional disturbances and a sharp decline in the cognitive development of an individual. In its most common form, symptoms usually appear when the individual is in their 40’s or 50’s. In the United States, approximately 300,000 people suffer from Huntington’s disease. Some of the early symptoms that are shown involve irritability, depression, lack of coordination, trouble in taking information, poor decision making and uncontrollable movements. While the uncontrollable movements first start as involuntary jerks or twitching known as chorea, as the disease progresses, the movements become more prominent. The disease has a less common form which is found in juveniles and it develops in the childhood stage. This also involves issues with movement, seizures, emotional changes, slurred speech and drooling. In this form the diseases progresses more quickly and it’s found that individuals with early onset Huntington’s diseases usually live bout 10-15 years after the symptoms begins to appear.
Genetic changes
The cause of the disease comes from the increased production of a single abnormal gene. In 1993, scientists isolated the affected gene in chromosome 4. This gene produces a protein known as “huntingtin,” which to this date, scientists are unaware of its function. The defective version of the gene repeats the sequence “CAG.” While in a normal Huntingtin gene, the sequence repeats between 11 and 29 times, in a mutated gene, it repeats from 40 to more than 80 times. This defect then causes the malformation of the Huntingtin gene which produces clumping in the brain and causes nearby cells to die. The cells that are affected are located in the basal ganglia which is a part of the brain that is responsible for the coordination of movement and of the cortex which controls an individual’s thoughts, perception and memory.
Diagnosis
In order for an individual to prepare for what they’re going to face when Huntington’s disease symptoms begin to appear, they need to be diagnosed. There is a genetic test that is used to confirm the diagnosis of Huntington’s disease. The test is carried out by gathering a blood sample and analyzing the DNA for the Huntingtin gene and counting the amount of CAG sequence repeats that there is in the gene. While individuals usually decide to take the test when their symptoms begin to appear, prospective parents prefer to do prenatal testing when one parents have been diagnosed with the disease or they know that they have the gene. In order to test the fetus, DNA is removed from the fetal cell by the method of Chorionic villi sampling and amniocentesis.
Inheritance
The gene that carries the disease is dominant which means that each child of a parent that has the Huntington disease gene is going to have a 50% chance of inheriting the gene. The child needs to exposed to only one copy of the gene in order to develop the disease. Upon inheriting the disease, sooner or later, during the mid-life, the diseases’ symptoms will start appearing. However, if the child doesn’t develop the defective gene, they will not get the disease nor will they pass it on to the incoming generations.
Treatment
Although there is no cure for Huntington’s disease, there are treatments which intend on decreasing the course of the disease and to facilitate as much comfort as they can to the individual. The treatment strategies that are readily available today involve medications used to target the specific symptoms that arise from the disease, such as the involuntary movements and behaviors, and depression.
KENNEDY DISEASE
Spinal and bulbar muscular atrophy, or Kennedy disease, is an x-linked disorder that affects the nerve cells which are in charge of controlling the motor neurons. These nerve cells originate in the spinal cord and in the brain stem. This condition affects about 1 in 150,000 males. Kennedy’s disease mainly affects males and it involves muscle weakness and wasting that usually begins in adulthood and progressively worsens over time. Some of the symptoms include cramping in the arms and legs, weakness in the leg muscle can lead to difficult in walking which results in the individual falling. Some muscles located in the face and throat are also affected which results in problems with swallowing, speech and muscle twitches are also common. Some males also develop breasts and can be infertile.
Genetic changes
Kennedy’s disease results from a mutation in the AR gene, which is a gene that is responsible for providing a manual of a protein called the androgen receptor. This receptor attaches to hormones called androgens that are involved in the male sexual development. The mutation that causes Kennedy disease is in the DNA segment CAG. Normally, the CAG sequence is supposed to be repeated about 36 times but in people with the disease, it’s repeated about 38 times and its two or three times its usual length. This extension in the CAG region has been proven to change the structure of the androgen receptor but scientists are still unsure of how the altered protein alters the nerve cells in the brain and spinal cord.
Inheritance
The condition is considered an x-linked disorder because the mutated gene that causes the disorder is found in the X- chromosome. In most cases, males suffer more severe symptoms of the disorder while females have mild features like muscle cramps and occasional tremors. A characteristic of X-linked inheritance is that affected males cannot pass X-linked traits to their sons, because they only pass their Y chromosome to their sons. However, all daughters of an affected male will be carriers of the condition. A female carrier of an X-linked recessive condition has a 50% chance to pass the mutated gene on to each daughter a 50% chance to pass the mutated gene on to each son.
Diagnosis
In order to diagnose the disease, it can be difficult. Doctors usually tend to look at an individual’s medical history, symptoms, physical examinations, and any possible laboratory tests that have been conducted in order to diagnose the conditions. Like Huntington’s disease there is no cure for Kennedy’s disease. The treatments that are available have a goal of reliving any symptoms that may be felt, and to try to decrease as much comfort as possible. Some of the treatments that have been deemed to be the most helpful have been physical therapy and rehabilitation, including the use of braces and walkers. These tools enable the person to move around even as the disease progresses. Since some males do experience a growth of breasts, they prefer to have a surgical breast reduction procedure. Also, doctors have investigated some tips that help individuals with Kennedy’s disease. For example, the symptom of bulbar weakness may cause asphyxiation and aspiration pneumonia. In order to prevent this, it’s recommended that they cut their food into smaller pieces and to avoid food items that are difficult to chew and swallow.