S C R I B E

After we turned in our homework and talked a little bit about the recent quiz we took about pedigrees and punnett squares, we discussed how people can prove what disorder someone has just by looking at them. You can do that by looking at their karyotype. A karyotype is the standard arrangement of all the chromosomes.
We then discussed how there can be 3 copies of a gene in the same chromosome. Those chromosomes are called trisomy 13, 18, and 21. The trisomy usually codes for Down syndrome, Edwards syndrome, and Pataynu syndrome. We also begin learning about Genetic Engineering which is changing DNA for practical purposes. For example, transgenic organisms have many applications in agriculture (make fruit grow faster, bigger, quicker, etc.). We finished off the day by watching a short video.

Genetic Disorder

Sickle Cell Anemia

Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape. Symptoms include, fever, swelling of the hands and feet, pain in the chest, abdomen, limbs, and joints, nosebleeds and frequent upper respiratory infections, fatigue and shortness of breath (signs of anemia), irritability, jaundice (yellowish discoloration of the skin and eyes), delayed puberty (in young teenagers), severe joint pain, progressive anemia, Leg sores, gum disease, vision problems. Blood tests can determine whether an individual has sickle cell trait or sickle cell disease. Treatment goals for sickle cell disease aim to relieve pain, prevent infections, and manage complications. Antibiotics, usually penicillin, are commonly given to infants and young children, as well as adults, to help prevent infections. Pain relief medication ranging from nonprescription nonsteroidal anti-inflammatory drugs (NSAIDs) to opiods are given to control pain. Hydroxyurea is prescribed for patients with moderate-to-severe sickle cell disease to help reduce the frequency of pain episodes and acute chest syndrome. There has not been a method proven to prevent sickle cell disease. But by taking the correct precautions to health problems is showing patients to live longer. The expected life expectancy with sickle cell disease is 42 years old for males and 48 for females.

Genetic Disorder

Neimann Pick Disease

Genetics: Neiman pick type A and B are caused by the mutation of SMD1 gene and Neiman Pick type C is inherited by the mutation of NPC1 and NPC2. Neiman Pick is inherited in which lipids get collected in the spleen, liver, and brain cells.

Symptoms: Spleen and liver enlargement, decrease of an appetite, pain in the abdominal, red spot on the eye, Jaundice, Seizures, Tremors, troubles moving the eye up and down, sudden loss of muscle tone, irregular speech, learning difficulties, difficulty of the movement of limbs are all symptoms of Neiman Pick.

Diagnosis and detection: For type A or B the diagnosis is a biopsy of the bone marrow or blood sample. For type C a small sample of skin in tested to see how cells move and store cholesterol.

Treatments: There are no treatments for type A but for type there is a treatment to transplant the bone marrow, enzyme replacement therapy, and gene therapy. For type c there is a new treatment called miglustat. There is no treatment for type D.

Prevalence: Neiman Pick occurs once every 1500 children. Hispanic people are more frequent.

Life expectancy: Usually 2 to 3 years.

Huntington's Disease

Huntington's disease is found on the 4TH chromosome. It is INHERITED if one or both of your parents have the dominant allele, then you would either have a 25% of having it or a 75% of having it (only depending if one or both of your parents has it). It gets passed down from family to family and either begins in the middle of your life, 40-50, or in the childhood of your life. The CAUSE of it is when both of or one of your parents has the disease. This als determines which type of Huntington's disease you would get. The two types are EARLY-ONSET or ADULT-ONSET untington's disease. The CAG gene is usually repeated 10-28 times, but in Huntington's disease case it is repeated 36-120 times.

SYMPTOMS/SIGNS/DIAGNOSIS

- Behavioral disturbances

- Hallucinations

- Irritabality

- Moodiness

- Restlessness or fidgeting

- Paranoia

- Psycosis

- Abnormal reflexes

- Hesitant in speking or annunciation

TREATMENTS

- Dopamine blockers may help reduce abnormal behaviors

- Medicines such as amantadine and tetrabanazine control extra movements

PREVELENCE IN POPULATION/ LIFE EXPECTANCY

In about 100,ooo people 6 or 7 of them will have Huntington's disease worldwide. It is also more common in the western half of he world. For people who have this disease their life expectancy will be 15-20 years after they get it.

Cystic Fibrosis

Cystic Fibrosis is usually
found in chromosome 7. There are many symptoms to this disease including coughing or wheezing, great illnesses, weight loss, and salty-tasting
skin. Cystic fibrosis attacks the lungs, which causes them to clog up.
Most people who have the disease only live till thirty years old. People with
the disease have about 5 times more salt in their sweat. There is currently no
cure for this disease, but treatments are being made. Some treatments are gene
therapy, inhaled antibiotics, and chest therapy. About 2,500 babies are born
with cystic fibrosis each year in the U.S. Affected people live near thirty
years old.

Genetic Disorder: Cri du chat

Hello, it's time for Disorder diseasification with Riaz! Today's messed up disorder: Cri du chat syndrome. French for "cry of the cat", Cri du chat syndrome is a disorder where an infant's cry is the sound of a meowing cat. Mostly caused by an abnormal larynx, it is mostly a factor of a broken or deletion of a chromosome when the embryo is in development. It is mostly not genetically inherited, because the break of a chromosome is autosomal. It appears 1 in every 50,000, life expectancy is also normal. Symptoms are as followed: low set ears, low birthweight, small jaw, small head, bad language skills, and mental retardation. It is hard to diagnose this disorder, because after age 2, the cry disappears. One could test for this while the baby is in the womb, or the child can qualify for language improvement classes. This is a picture of a person with cri du chat syndrome. Take a look, if you dare!

Bloom's Syndrome

Bloom's Syndrome

Causes

1. Changes in the gene (BLM). BLM is responsible for copying and repairing cells.

Life Expectancy and Diagnosis

• What you can look for in to see if the person has Bloom's syndrome, is to see breaks in individual chromosome's.
• Bloom's syndrome, currently has no cure,and the life expectancy is at age 27.

Detection

• You can detect it by going to the doctor and see if you have the symptoms.
• chromosome testing, or testing of the Blooom's syndrome gene.

How Common it is

• 1 and 110 is the carrier frequency
• 98% of Ashkengzi Jewish people, are carriers
• It is an autosomal reccesive disorder
• It is not sex linked so you have to inherit this disease by both parents.

Symptoms

• You have little body fat
• In some cases, you have mild mental retardation
• Sensitive to sunlight

PKU

PKU (phenylketonuria) is a genetic disorder that can lead to brain damage in babies. It is an autosomal recessive disorder, that is found in babies. It is found on chromosome 12. PKU happens when the PAH protein is mutated, and becomes unable to break down the amino acid phenylalanine.

To the left is a picture of Chromosome 12, and the PAH gene is in red.

Doctors treat babies for PKU by testing every newborn baby in the US. They do this, because the disease is so common, and it has to be treated for very early in the babies life, that it is the only reasonable solution.

People with PKU treat it by not eating any protien, because almost every protein has phenylalanine, and if the person who has it eats phenylalanine, it doesn't get broken down properly.

PKU is fairly common in the United States, about one in every 15,000 babies in the US is born with PKU.

Gaucher Disease

Gaucher disease is a rare genetic disorder when a person does not have enough of an enzyme, glucocerebrosidase, that breaks down the fat glucocerebroside. People who have the disease do not have enough glucocerebrosidase, so it builds up in the liver, the spleen, bone marrow, and nervous system, that prevents the body from functioning normally. Gaucher disease is an autosomal recessive disease, meaning it is inherited when both parents have the disease. It it caused by mutations in a single gene called GBA, which lead to low levels of glucocerebrosidase. So, someone who has Gaucher disease inherits a mutated copy of GBA from both of their parents. The disease happens in about 1 in 50,000 to 1 in 100,000 people in the general population. The people at highest risk for the disease are people of Ashkenazi Jewish ethnicity. There are three types of Gaucher disease- type 1, type 2, and type 3. Type 1 is the most common, and the effects are bone disease, anemia, and a bigger spleen. Type 2 happens to babies and can result in an early death. Type 3 can cause spleen, liver, and brain problems, and the life span is to adulthood. The signs and symptoms of the disorder are bone pain and fractures, cognitive impairment, easy bruising, a bigger spleen, a bigger liver, fatigue, heart problems, lung disease, seizures, severe swelling, and skin changes. Gaucher disease is diagnosed by a variety of tests- blood test, MRI, CT, X-ray of the skeleton, and genetic testing. Enzyme replacement therapy is available as treatment, and so is bone marrow transplants. Adults with type 1 disease usually live a normal life expectancy, but most diagnosed children die before the age of five.

Galactosemia!

Galactose is a food sugar found mainly in dairy products, especially milk. The ability for the body to break

down galactose comes from a specific enzyme. People with galactosemia lack this enzyme. So, their bodies cannot digest galactose properly, and it builds up in their blood. Galactosemia is an autosomal recessive genetic disorder.

The gene that codes for this enzyme, galactose-1-phosphate uridyl transferase (GALT), is located on chromosome 9. Many different mutations within this gene have been identified, and the most common mutation is called "Q188R". People with galactosemia have this mutation. A milder form of galactosemia, called the "Duarte variant", is also caused by a mutation within the GALT gene. Different changes within the GALT gene are what lead to variations in enzyme levels between individuals with galactosemia.

A person is diagnosed with Galactosemia as an infant, through a routine test of taking a blood sample from the heel right when they are born. The only treatment for a person with this disease is to adjust their diet. The goal of dietary treatment for galactosemia is to minimize galactose intake, which in turn minimizes galactose-1-phosphate production.

It is not possible for a person with galactosemia to have a galactose-free diet, because there is at least a tiny bit of galactose in everything. However, all persons with galactosemia should limit galactose intake from foods to a very low level. The galactose-1-phosphate levels of the individual determine the degree of dietary restriction necessary. If this strict diet is not followed, many problems can arise in the patient, like cataracts or liver problems.

However, as long as they adjust their diet accordingly, people with Galactosemia are expected to live a normal life expectancy, unless they are complicated with other problems or disorders.

Wolf-Hirschhorn Syndrome 101

Genetics of the disorder:

• Wolf-Hirschhorn Syndrome is causes by a genetic error in the 4th chromosome, a deletion of genetic material near the end of the short (p) arm of chromosome 4. It can be inherited from the parent chromosome where there is a chromosomal translocation (rearrangement of parts between nonhomologous chromosomes).

Symptoms/Signs include:

• Distinctive facial features: small head, large forehead, broad-beaked nose, wide set (far-apart) eyes (resembles a “Greek warrior helmet”)
• Heart defects
• Malformations of hands and feet, chest, and spine
• difficulty eating and/or swallowing
• Low muscle tone
• Poor muscle development
• Mental retardation
• Seizures

Diagnosis and Detection:

• Children born with Wolf-Hirschhorn syndrome can be diagnosed by an ultrasound or by appearance at birth. The distinctive facial features are a major sign of the disorder. Tests such as renal ultrasonography that look at the kidneys, x-rays that look for bone and internal malformations, and magnetic resonance which produces images of the brain can also be taken to diagnose the disorder.

Treatment and therapy available:

• No treatment exists for the genetic disorder itself, but there are treatments available for the symptoms of the syndrome. Seizures can be treated with medication, and difficulty eating or swallowing can require a feeding tube. Physical therapy can help maintain muscle strength and mobility.

Prevalence in the Population:

• Wolf-Hirschhorn syndrome affects females more frequently than males, and occurs in people of all ethnic backgrounds. It is estimated to occur in 1 in 50,000 births.

Life Expectancy:

• The life expectancy is unknown, but is likely lower than an individual without the disorder. Many members of the disorder are in their 30’s and 40’s. The oldest person with the disorder was born in 1949.

Loeys-Dietz Syndrome

Loeys-Dietz is inherited. The mutated syndrome is dominant. Meaning, only one parent needs to pass on the gene in order for its offspring to develop this syndrome.

The signs and symptoms include abnormal organization of blood vessels. Many affected children have physical/facial features that is the first abnormality that is recognized. Symptoms include the following

• early fusion of the skull bones
• widely spread eyes
• cleft palete

Loeys-Dietz syndrome may be diagnosed by injecting a dye into the blood vessels that is visable by x-ray.

The only treatment for Loeys-Dietz syndrome is surgical repair of the aortic aneurysm.

The prevalence is unknown. There have not been any ethnic, racial group, or gender preferences reported.

Life expectancy for Loeys-Syndrome is 23 years old.

Fragile X Syndrome

Fragile X syndrome is a common form of mental retardation. This occurs when the FMRI gene- which produces protein, lacks the process of making protein. Some of the signs and symptoms are as follows

•   People with this disease have an affected ability to think, reason, or learn because of an impaired intellectual function
• At a young age, physical appearance is very slim, light skin, not much hair etc. But as the child hits puberty in their teen years they start to develop adult traits such as a longer face or jaw.
• People with Fragile X syndrome are very stressful and become upset very easily.
• Kids who try and speak either stutter somewhat or can have very large problems speaking words at all
• Anything that makes a loud or unexpected noise can be heavily disturbing to people with Fragile X syndrome 

The gene FMRI is shown by the nucleotide triplet CGG which appears 6 to 50 times in an unaffected person. To detect if one has Fragile X syndrome they look for how many sequences of CGG you have and make sure it is in that range. If not they diagnose you with the syndrome.
While there is no cure or treatment, there are many therapies to get somebody through this disorder.
Putting the child through a special education class everyday is one option, and another is letting him/her be in a regular class to experience what it is like. There are also physical and occupational therapists as well as speech and behavioral.
This disorder is more common in males and about 6,000 to 10,000 people are diagnosed with it every year.

Sickle Cell Disease

Sickle cell disease is a mutation in the blood protein. It changes the shape of the red blood cells and changes their functions and behavior. These cells become sticky, stiff, and sickled and they can cause severe pain and extreme organ damage. This disease is inherited through genes of the parents, averaging a 25% chance per child, or a 1 in 4 chance. The disease is mostly found where mosquito born milaria is present, therefor it is the most common single cell disorder among African Americans and 1 in every 375 inherit this disease. All around the world 250,000 people on average are born with sickle cell disease each year. It is most commonly found in Africa, the Mediteranean, Arabia, and South Asia. Test for diagnosis are performed at birth called hemoglobin electrophoresis where the blood is sampled. Sickle cell disease can also be detected in an unborn fetus. The most obvious symptom is pain, which is associated with blocked blood vessels which can be severe enough for hospitalization. It can damage the spleen, lungs, and heart as well as strokes. Many cases develop anemia which leads to fatigue. There are 3 distinct types of the disease which include sickle cell anemia, SC disease, and SB disease. People with the disease have a shortened life expectancy with studies showing and average of 42 for males and 48 for females. Blood transfusions help lessen the symptoms as well as narcotics used to help lower the amount of pain. The drug hydroxyurea help prevent sickle cell's complications. The only known cure for the sickle cell disease is a bone marrow transplant but is a very high risk operation. It is more successful for kids while most adults have a tendency to reject the transplant.

Marfan's Syndrome

Marfan’s syndrome is a disorder that affects connective tissue. Connective tissue helps support many parts of your body and holds all your limbs together. When a person has Marfan’s syndrome, their skeleton, heart, eyes, skin, nervous system and lungs are the most common body systems that can be affected. This disorder shows in many different ways. Some have mild symptoms and others have severe symptoms. Some severe symptoms include a collapsed lung, numb legs, a hernia, a heart murmur, or a curved backbone. Mild symptoms include having a long, narrow face, crowded teeth, nearsightedness, stretch marks, and snoring while sleeping. This disorder is caused by a defect in the gene that produces fibrillin. Fibrillin is a protein that makes up connective tissue along with other proteins. Fibrillin is also located on chromosome 15. All people are known to get Marfan’s syndrome. This includes: men, women, children, all ethnic groups and races. When someone thinks they have this disorder, their first step is to visit a medical geneticist. There they can determine if the person has the defected gene. There is not cure yet for Marfan’s syndrome but a lot of treatments can treat symptoms that occur. There are different treatments for each of the body systems. For example, if ones eyes are affected, regular eye check-ups are highly recommended because the doctor can catch and fix any eye problems that are expected. Usually, glasses can correct problems associated with Marfan’s Syndrome. People with Marfan’s Syndrome but do not realize, can die within 48 hours of having symptoms such as chest pains. But, if people catch it early enough and learn how to coupe with the disorder, people can live normal lives.

BETA THALASSEMIA!!

Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout of the body. In people with beta thalassemia, low levels of hemoglobin lead to the lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells, which can cause pale skin, weakness, fatigue, and more seriosoud, complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots. Beta thalassamia is classified into tw o types depending on the severity of symptoms: thalassemia minor and thalassemia major. Of these two types, beta thalassemia major is much more severe. The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threating aneamia. They dont gain weight and grow at the expected rate, and may devlop yellowing of the skin and whiting of the eyes. For children with thalassemia minor, the symptoms may appear in early childhood or alittle later in life. Affected people have mild to moderate anemia and may also have slo growth and bone abnormalities. Beta thalassemia is a fairly common blood disorder worldwide. Thousands of infants with beta thalassemia are born each year. Beta thalassemia occurs most frequently in people from Mediterranean countries.

Canavan Disease

Canavan Disease is a genetic disorder that affect the use and breaking down aspartic acid, or nonessential amino acids that takes part in hormone production and release and in the nervous system. Canavan is caused by a mutation in the gene that lacks the enzyme aspartoacylase (ASPA), which breaks down a chemical in the brain called N-acetylaspartic (NAA). This chemical destroys myelin, fat that surrounds the white matter of the brain containing nerve fibers. Both parents have to be carriers in order for their offspring to be infected with the disease.

Symptoms are:

• Deficieny in motor developement


• Struggles in feeding


• Weak or stiff muscle tone


• Abscence of head control

Other disabilities such as blindness, paralysis, loss of hearing, and mental retardation can occur. Canavan Disease can be indentified by a blood test, screening for mutations or absence of the enzyme. Treatment mainly target to ease any symptoms of the disease, but several drugs are being researched. The disease is mostly common among Ashkenazi Jews. One out of four children could be infected with the disease. Infants do not live before 18 months, and children die before the age of 10. But several are able to survive into their teens and twenties.

Duchenne's Muscular Dystrophy (Genetic Disorder)

Duchenne's muscular dystrophy is a x-linked recessive disease. It is a fast progressive form that is caused by a mutated gene and occurs mostly in boys. The probability of passing this disease to females and males are different. Since a male has x and y chromosomes, if that child's x chromosome has DMD gene mutation, then the child will inherit Duchenne's muscular dystrophy. (DMD encodes the muscle protein, dystrophin.) On the other hand, a female has two x chromosomes, so if they only have one gene mutation, they are considered a "carrier", but if they have two mutated gene, they will have the disease. Recently, 20% of women who are carriers had symptoms such as, muscle weaknesses, or cardiac abnormalities. Women who are carriers have 50% chance of passing on, and 25% chance of getting babies affected with DMD. Gonadel mosaicism is when a person has 2+ cell populations that differ in genetic makeup of eggs and sperms, and the change in the dystrophin gene is a new genetic change.

The symptoms usually start at ages 1-6. Sitting and standing may become difficult. The loss of pelvic and leg muscles cause replacement of fat in those parts of the body. Muscle decline also happens in the arms, neck, and upper body as well, but it's not as severe as the lower half. Because of this, as they grow, their bones may be deformed or have cardiomyopathy (breathing disorders/ enlarged heart).

There are many diagnosis and prevention for Duchenne's muscular dystrophy. One is taking samples of muscle tissues, or muscle biopsy, to look for abnormal levels of dystrophin protein in muscles. Without muscle biopsy, looking at the body's genetic instructions on a blood sample to look for DMD is another good way of diagnosing. (Creatine kinase is highly concentrated in muscle cells, but the breaking of muscle cells go into the bloodstream, so if they are found there, that could answer whether the person has the disease.) Finding deletion/duplication in gene sequencing may also detect the changes in DMD gene. Family history, blood tests, and muscle biopsy can determine the whether you have the disease or not.

Treatment of Duchenne's muscular dystrophy is aimed at the symptoms. If cardiomyopathy is severe, cardiac transplantation is used, but in most cases, doctors use anti-congestive medications. Medications such as prednisone, a steroid, to improve the strength of the individual. But this medication has many side effects, such as, high blood pressure, weight gain, and delayed growth. Cyclosporine is a medication that has improved clinical function in children, but the use of it is very concerning because of cyclosporine-induced myopathy. Oxandrolone, another medication still being studied, has fewer side effects. To prevent hardening of joints and deformity, physical therapy is essential during the process of medical treatments as well.

Duchenne's muscular dystrophies affect 1 in 3500-5000 newborn males. There are between 400-600 boys in the U.S. born with Duchenn's muscular dystrophy every year. There are also girls affected by this disease, but it is very uncommon. There were shocking amount of cases of this disease in the northern region of England. There isn't a direct answer to this mystery, but all we know is that gene mutations have caused it. But generally, Duchenne's muscular dystrophy can be found all over the globe.

Life expectancy for this specific disease is pretty young because the symptoms, such as cardiomyopathy and muscle decline is dangerous and very unhealthy for the body to endure for long time, so the heart can fail easily. Most don't live over 30, because of the breathing complications.

Hi it's Jessie. My genetic disease is Maple Syrup Urine Disease. Maple Syrup Urine Disease is a mutation of the BDKDHA gene on chromosome nineteen. This mutation enables the body to break down leucine, isoleucine, and valine, amino acids. These acids are used to make proteins, but when not being used they a

re broken down or recycled. This is done by 6 proteins working together. They form a complex called branched-chain alpha-ketoacid dehydrogenase or BCKD. If a person has Maple Syrup Urine Disease, they are missing one of the six proteins needed in BCKD. This causes levels of leucine, isoleucine, and valine to become dangerously high and rapidly kill brian cells or cause death if left untreated. Maple Syrup Urine Disease has an autosomal recessive inheritance, meaning you need two of the defective genes to get Maple Syrup Urine Disease.

Because the disease is so severe a person who has it will not live past there first few month of life. All people are diagnosed with Maple Syrup Urine Disease are diagnosed as a baby. The symptoms are loss of appetite, fussiness and sweet smelling urine. If these symptoms occur a blood sample is taken from the

baby and analyzed, but some hospitals do this within 24 hours after the birth. If high levels of leucine are present the baby is put on a special baby formula that does not contain the amino acids. That person then must stay on a special diet for the rest of their lives. If levels of leucine, isoleucine, and valine still get to high, patients can be treated with intravenous solution, given through a vein. This helps the body use up the extra leucine, isoleucine, and valine.

Maple Syrup Urine Disease is extremely rare. Only 1 in 180,000 babies are born with Maple Syrup Urine Disease. Although this disease is rare, in the Mennonites in Pennsylvania, 1 in 176 babies is born with Maple Syrup Urine Disease. Also, in Ashkenazi Jews, 1 in 81 babies os born with Maple Syrup Urine Disease.

If not diagnosed early enough the baby will die within a few mouths. If diagnosed though, the person can have a normal life span if amino acid levels are kept under control.

Tay-Sachs Disease

Hi guys! Heidi here.

My genetic disorder was Tay-Sachs disease. Tay-Sachs disease is a disease of the nervous system passed down through people who are from the Ashkenazi Jewish population. Tay-Sachs disease is caused by a defective gene on chromosome 15.

Some symptoms are:

• deafness
• blindness
• loss of muscle strength
• delayed mental and social skills
• loss of brain function
• increased startled reaction
• irritability
• loss of motor skills
• loss of muscle function
• seizures
• slow growth

You can get tested for Tay-Sachs disease before the child is born by a physical examination.

If the child had a seizure of an unknown cause or if they were different from other seizures, if the child had difficulty breathing, or if the seizure lasts longer than 2-3 minutes, the child might have Tay-Sachs disease. There are no existing treatment for Tay-Sachs disease.
Although there aren't any existing treatment all you can do is make the child comfortable. 1 in every 27 members of the Ashkenazi Jewish population are carriers. Most people who have this disease usually die at age 4 or 5, their symptoms are shown when they are 3-6 months old.