Genetic Counseling : Genotyping and Incompatibility.Keane and Barbie were childhood friends. They grew up in the same neighborhood and attended the same kindergarten school. Their grade school, middle school,high school and college were also the same. They both had the highest grades in all their classes. They liked each other and were basically inseparable. While in college, Keane discovered he had more than platonic feelings for Barbie and he disclosed this to her. Barbie who also shared the same feeling and had been waiting for Keane to say something since high school, so she was eager to start a relationship and thus they started dating. A relationship based on pure love and friendship. They had a wonderful relationship with minimal misunderstanding and a lot of true love. Years later, after dating for over five years, after college and getting jobs, they decided to get married.Then things went south… A friend of Barbie’s suggested that they both took genetic testing to check for their compatibility. Keane was reluctant at first but after persuasion from Barbie, he was convinced into taking the test. The test results came out and the geneticist informed them that both of them had type ‘AS’ blood and Keane tested positive for ‘Rh’ antigen while Barbie was negative. They were both confused about the implication of their lab test. On seeking further counseling, they were advised to forget about marriage because they had a 25% of producing an offspring with sickle cell. Love prevailed and they went ahead with marriage. In no time, Barbie grew a bump and months later when the baby was delivered, the child turned out to be a sickler. Years passed and the overwhelming medical expenses for taking care of the child who was constantly getting ill drove both parents to bankruptcy and at the depths of their desperation and depression, they decided to pull the plug and euthanize the poor kid due to insufficient funds.Two years passed and the deteriorating marriage was to be saved by another pregnancy as both parents had finally decided they were over the death of their first child. Of course, this time they didn’t have as much money as they did the first time and ended up at a local hospital with poor facilities. No ante natal treatments or testings were administered. Merely minutes after the baby was delivered, the baby haemolytic reactions which lead to jaundice and other complications killed the baby. It was later diagnosed that Rh incompatibility had lead to the series of complications that killed the child. The essence of this short story is to put forward the notion that no matter how good the relationship is or seems, genotype incompatibility is not an issue to be taken with a pinch of salt before walking down the aisle. The concept of genotyping will be revised in the following passage.Genotype is the genetic composition of an individual.An human genotype consist of two alleles which are a pair of alternative contrasting characters transferable , one from each parent, to the offspring. An homozygous Gene has the same allele from each parent while an heterozygous one has a different allele from each parent.#### Why is this important?.
It is important because each parent donates half of their genetic information to their offspring. This means that each child given birth to is basically half of the father and half of the mother. Several genotype exist for various body functions but the one to be discussed is the genotype for hemoglobin content. The hemoglobin genotypes that are being discussed are AA, AS and SS. Although others exist but these are the most common. A short note on Blood groups and incompatibility is also added at the end. #### AA Genotype
This is an homozygous genotype because the individual inherited the same genetic material for the hemoglobin content. It is the normal hemoglobin genotype. It is homozygous for hemoglobin which has all the constituents of the hemoglobin at the molecular level. People with AA blood group almost never have problems related to blood group anomalies although they show a high susceptibility to malaria. #### AS Genotype
This is an heterozygous genotype in the sense that the individual inherited a different genetic material from each parent- in this case, a normal ‘A’ and an abnormal ‘S’. The ‘S’ allele Is a mutated form of hemoglobin which is believed to have been caused by the body trying to adapt to the malaria parasite. AS blood group is usually called Sickle cell trait because the individual has normal red blood cells and a few abnormal ones showing signs of sickling. People with AS genotype are usually normal with barely any negative effects from the mutated hemoglobin ‘S’. The only effect the mutated *’S’* gene has is that it provides a form of resistance from the malaria parasites. #### SS Genotype
This is another homozygous genotype where no normal hemoglobin genetic material is inherited from each parent. Both genetic materials inherited causing blood sickling. SS genotype is more commonly called the ‘Sickle cell disease’ This is because all the red blood cell constituents of the individual lose their normal biconcave shape and become sickle shaped thereby rendering the red blood incapable of effectively performing it’s functions like oxygen and nutrient transport which could cause problems such as hypoxia or blockage of blood vessels which could cause an infarction. Genetic counseling is an efficient means to sensitive people to the ills that could be wrath by something as trivia as a mismatch of parental genotype mismatch. Usually, the advice given is for the parents to split up but in this article only solutions that do not involve the couple splitting up will be preferred. #### THE TRANSFER
Before you can think of preventing the genotype incompatibility,you should first know how it is passed down from parents. After understanding the basics that each individual has an hemoglobin genotype which could be AA, AS or SS. We are going to be considering the possible outcomes of reproduction by parents with different combinations of genotype. The probability of producing offsprings with certain genotypes is usually calculated via a punnet square of a simple crossing diagram. Consider the table below:AA + AA = AA, AA, AA, AA.AA + AS = AA, AS, AA, AS.AA + SS = AS, AS, AS, AS.AS + AS = AA, AS, AS, SS.AS + SS = AS, SS, SS, SS.SS + SS = SS, SS, SS, SS.It can be seen that the only combinations where offsprings with Sickle cell disease are those where both parents AS,where one parent is AS while the other is SS and when both parents are SS. Although the probability of having a sickle cell offspring is different for each scenario, it is however unwise to test fate because the probability applies per birth. That is,if both parents are AS, they have a 25% chance of producing a child with SS genotype each time the female parent gets pregnant. The solutions for intending couple’s who fall into categories where there is a chance for producing sickle cell offspring are listed in the following sentences. #### CONSIDERING ADOPTION
Adoption is the first and most easy solution. All that is required is to sign some legal documents after qualifying for the role. The draw backs of adoption could be the stigma of not being able to have one’s own biological offspring due to a chance of having an illness and the fact that most people are not able to show enough live to the adopted child like they would have done if it were their own kid. #### PRENATAL TESTING
Another profitable solution would be prenatal testing such as amniocentesis or choruonic villi samplinh which is done by aspirating fluid from the conceptus and testing for any genetic malformations. If the fetus has sickle cell genotype the parents have a chance of whether to abort or not but if the fetus doesn’t have the sickling genotype, the pregnancy is kept. It should be noted however that marriage between SS parents should not be attempted because there is an 100% probability of having offsprings with sickle cell disease. #### RHESUS FACTOR
Rhesus incompatibility, another form of genetic mismatch which could cause fatal complications is worthy of note. ## *What is Rhesus factor?*Rhesus factor is a blood cell antigen found on red blood cell membrane, saliva and pancreatic secretions. It was first discovered in the rhesus monkey, hence the name rhesus factor. Individuals with the D antigen present in the body are said to be Rhesus positive while those without the antigen are said to the Rhesus negative. #### How does Rhesus incompatibility work? You would remember from the story illustrated at the outset of this article that the lady was Rhesus negative while the husband was Rhesus positive. The Rh antigen is inherited from the father by the baby despite the mother not having the Rh antigen. The body’s immune system produces antibodies which are like soldiers that fight of invasion of both toxic and foreign substances. The Rh antigen is a foreign substance in the body of An Rh negative individual so the immune system of the Rh negative individual would produce antibodies against the Rh antigen which would lead to a clotting reaction and/or hemolytic reactions. During the first pregnancy(Rh negative mother with Rh positive baby), the fetus is usually safe because there is no flow of blood from the fetus to the mother and thus there is no formation of antibodies. But during detachment of placenta at birth, part of the fetal blood is deposited into the maternal circulation and Rh antibodies are produced. A second pregnancy is however not as lucky as the first because the antibodies produced by the mother remain in circulation for a long period. During fetal life there is flow of blood from maternal circulation into the fetus and along with the blood being passed across, the Rh antibodies of the mother are also being taken up by the fetus. If the second conceptus is Rh positive( which almost always the case if the father is Rh positive),the baby develops an hemolytic reaction as a result of the mother’s anti Rh antibodies attacking its D antigen and causing destruction of the blood cells. ### JAUNDICE
Jaundice is the first sign of hemolytic disease in a new born. It occurs due to excessive hemolysis of red blood cells. It presents as yellowness of the sclera and pallor of the lips and limbs. Kernicterus could also occur. This is a form of fetal brain damage where bilirubin formed from the hemolyse blood cell cross the poorly developed blood brain barrier and causes irreparable brain damage and death. Fetal hydrops also presents in the form of premature red blood cells in the blood stream. This is caused by the spleen trying to compensate for the excessive loss if red blood cell due to hemolysis. The spleen produces red blood cell and when they become extremely low in circulation, erythropoiesis which creates red bleed cell is stimulated. However,the red blood cells are needed immediately and the body can’t wait for the red blood cells to mature and cells at different stages of development are released into circulation. Premature red blood cells,except reticulocytes cannot perform the function of mature red blood cells. Preventive measures and treatments for Rh incompatibility disease (hemolytic disease of newborn) include the following. Prenatal should be carried out to determine the Rh status of both the mother and the child. If the mother tests negative for Rh antigen and the fetus is positive, anti Rh antibodies should be introduced into the mother at 28th and 34th weeks of gestation as prophylactic. Rh antibodies are then administered to the mother 48hours after delivery of first Rh positive baby so that the mother develops passive immunity which fades over time while preventing the formation of Rh antibodies by the mother. On the other hand, if the baby is born with hemolytic disease, exchange transfusion could be done whereby the infant’s Rh positive blood is replaced by Rh negative one. It will now take at least 6 months for the infant’s own Rh positive blood to replace the transfused Rh negative blood. At this time, all traces of Rh antibodies gotten from the mother would have gotten destroyed.The role of genetic counseling and knowledge of blood group and genotype cannot be overestimated and it’s importance is quite significant. Therefore,before you say yes to that marriage proposal,visit a geneticist to test for compatibility and for counseling.