Genetics of Sickle Cell Disease

Genetics of Sickle Cell Disease

Sickle cell disease is an inherited condition. Two genes for the sickle hemoglobin must be inherited from one's parents in order to have the disease. A person who receives a gene for sickle cell disease from one parent and a normal gene from the other has a condition called “sickle cell trait”. Sickle cell trait produces no symptoms or problems for most people. Sickle cell disease can neither be contracted nor passed on to another person. The severity of sickle cell disease varies widely. Some people with sickle cell disease lead lives that are nearly normal. Others are less fortunate, and can suffer from a variety of complications.

Heredity of Sickle Cell Disease

 During fertilization, a person receives one set of genes from the mother (egg) and a corresponding set of genes from the father (sperm). The genes exist on structures inside cells called chromosomes. The combined effects of many genes determine some traits (hair color and height, for instance). Other characteristics are determined by one gene pair. Sickle cell disease is a condition that is determined by a single pair of genes (one from each parent).

 The genes involved in sickle cell disease control the production of a protein in red cells called hemoglobin. Hemoglobin binds oxygen in the lungs and delivers it to the peripheral tissues, such as the liver and muscles. Most people have two normal genes for hemoglobin. Some people carry one normal gene and one gene for sickle hemoglobin. This is called "sickle cell trait". These people are normal in almost all respects. People with sickle cell trait do not develop sickle cell disease as they grow older. People with sickle cell trait rarely develop problems related to their single sickle cell gene, and then only under very unusual conditions.

A person receives the sickle cell genes or not only at the time of conception. Therefore, neither sickle cell trait nor sickle cell disease can be contracted. By the same token, people cannot lose their sickle cell genes over time. A person born with sickle cell trait (one sickle cell gene) will always have sickle cell trait. The same is true of sickle cell disease (two sickle cell genes). Sickle cell disease produces illness, while sickle cell trait usually does not. The severity of sickle cell disease can change over time. The change in severity is not due to a change in the sickle cell genes over time. Rather, number of other biological factors, most of which are not understood; change to alter the severity of sickle cell disease.

 People who inherit two genes for sickle hemoglobin (one from each parent) have sickle cell disease. With a few exceptions, a child can inherit sickle cell disease only if both parents have one gene for sickle cell hemoglobin. The most common situation in which this occurs is when each parent has one sickle cell gene. In other words, each parent has sickle cell trait.

 At each conception, the probability of getting a child with two normal gene is 1/4 or 25% in all. Also  same 1/4  chance that a child will inherit two sickle cell genes, and have sickle cell disease while there is a high 50% or 1/2 probability that the child will inherit a normal gene from one parent and a sickle gene from the other and thus be a carrier of sickle trait. 

 These probabilities exist for each child independently of what happened with prior children the couple may have had. In other words, each new child has a one-in-four chance of having sickle cell disease. A couple with sickle cell trait can have eight children, none of whom have two sickle genes. Another couple with sickle trait can have two children each with sickle cell disease. The inheritance of sickle cell genes is purely a matter of chance. These probability odds cannot be altered.

Genetic Change that results in Sickle Cell Disease

Hemoglobin consists of four protein subunits, typically, two subunits called alpha-globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. One particular HBB gene mutation produces an abnormal version of beta-globin known as hemoglobin S (HbS). Other mutations in the HBB gene lead to additional abnormal versions of beta-globin such as hemoglobin C (HbC) and hemoglobin E (HbE). HBB gene mutations can also result in an unusually low level of beta-globin; this abnormality is called beta thalassemia.

In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. The cause of sickle cell anemia is a point mutation in the gene coding for hemoglobin. The change converts a glutamic acid codon (GAG) to a valine codon (GTG). The form of hemoglobin in persons with sickle cell anemia is referred to as HbS.

Valine has replaced glutamic acid which is present in normal hemoglobin and has resulted in sickle cell disease. 

The story of First adult that was cured of sickle cell disease

          

Iesha Thomas, a Chicago woman has been in and out of hospitals battling sickle cell disease since she was only 8 months old. 
Thomas, 33(as at June, 2012), had her first sickle cell crisis when she was just 8 months old. Her disease became progressively worse as an adult, particularly after the birth of her daughter. She has spent most of her adult life in and out of hospitals with severe pain and has relied on repeated red blood cell transfusions. Her sickle cell disease also caused bone damage requiring two hip replacements.

“I just want to be at home with my daughter every day and every night,” said Thomas, who depends on family to help care for her daughter during her frequent hospitalizations.

This type of stem cell transplant is only possible for patients who have a healthy sibling who is a compatible donor.

Thomas’ sister was a match and agreed to donate blood stem cells through a process called leukapheresis. Several days prior to leukapheresis, Thomas’ sister was given drugs to increase the number of stem cells released into the bloodstream. Her blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplant.

“Now, with this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just one month of the transplant,” says Dr. Damiano Rondelli, professor of medicine at UIC, who performed Thomas’s transplant.

This summer, 33-year-old Thomas became the first adult to be cured of sickle cell disease with a chemotherapy-free procedure at University of Illinois Hospital & Health Sciences System (UI Health), the University reported. Thomas is one of 12 adult patients cured of sickle cell disease as part of a clinical trial at UI Health that used a unique procedure for stem cell transplantation from healthy tissue matched from a sibling donor.

The Role of Worms in the Etiology of Asthma

Asthma and Worms: The role of worms in the Etiology of Asthma

About Asthma

Asthma is not a new name in the world.  According to WHO, Asthma is a chronic disease characterized by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. During an asthma attack, the lining of the bronchial tubes swells, causing the airways to narrow and reducing the flow of air into and out of the lungs.

Causes of Asthma: Can Worms contribute to Asthma Development?

The causes of asthma are not completely understood. However, risk factors for developing asthma include inhaling asthma “triggers”, such as allergens, tobacco smoke and chemical irritants. Asthma cannot be cured, but appropriate management can control the disorder and enable people to enjoy a good quality of life. The World Health Organization WHO estimated that Asthma affects 235 million people in the world. The real cause of Asthma is not fully understood.

 However, asthma is associated in all cases with tiny Ascaris larvae. As soon as eggs hatch (in the stomach, after ingestion) the microscopic larvae travel to the lungs, not the intestines. Imagine the distress of lungs full of tiny worms!

One tries to cough them up, of course, but in our misguided effort to be polite we teach children to swallow anything they cough up! Some swallowing is inevitable and the young worms are back in the stomach, this time to set up their housekeeping in the intestine. Some never leave the stomach, causing children stomach aches and, of course, a large entourage of bacteria which, in turn, have their viruses.

Most cases of Ascaris infestation also show Bacteroides fragilis bacteria which, in turn, carry the Coxsackie viruses (brain viruses). Whether or not these bacteria or viruses will thrive in you depends on whether you make a good home for them, namely have low immunity in some organ. The preferred organs for Bacteroides are liver and brain (brain tumors always show Bacteroides). The preferred organs for Coxsackie viruses appear to be tooth abscesses and brain.

Not everybody with Ascaris develops asthma, even though they always go through a lung stage. Does it depend on the age of the person when the infection develops? Or how many Ascaris are present? Or the time of year when lung infection is present?

That innocent cough of early childhood should not be neglected, as simply “croup.” At the first sign of a cough, treat immediately. Never neglect washing hands before meals.

Asthma sufferers become allergic to many air pollutants such as pollen, animal dander,smoke. The production of histamine in the lungs and the vast interconnectedness of histamine to allergies have been vastly studied scientifically. Although invasion by worms is known to result in both histamine production and high eosinophil counts (over 3), and asthma patients typically have both, they are not routinely checked for worms clinically! They are simply given drugs to enable better breathing. More and better (though toxic) drugs have been developed.

But you can put an end to your asthma by terminating your Ascaris infection. Then wash your hands and fingernails with grain alcohol, and avoid re-infection or ingestion. Wear plastic gloves for a week to break a nail biting or finger sucking habit. For children wash hands before eating anything, even between meals; keep fingernails short. Dogs, cats, pigs and horses all get Ascaris. So these pets should be sanitized or treated regularly.