Multiple Alleles and Blood Genetics

Mendel’s Principles – A Review Inheritance of traits is determined by genes. Genes are passed from parents to offspring. Alleles can be dominant or recessive. In sexually reproducing organisms – each adult has two copies of each gene – one from each parent.

Exceptions to Mendel’s Work Some alleles are neither dominant or recessive. Many traits are controlled by multiple alleles or multiple genes.

Multiple alleles Homologous chromosomes Chromosomes occur in pairs. (homologous mean “same”) The different alleles of a gene occupy the same positions on each chromosome

Multiple alleles So far each gene we have discussed has been made of two possible alleles.   Ex. B = blue b= yellow R = red r = white

Multiple alleles However, it is possible to have several different allele possibilities for one gene. Multiple alleles is when there are more than two allele possibilities for a gene. Coat color in rabbits is determined by a single gene with 4 possible alleles.

In rabbits, coat color is controlled by multiple alleles In rabbits, coat color is controlled by multiple alleles. Full color (C), white (c), light-gray or chinchilla (cch) and white with black points or a Himalayan (ch). Full color is dominant to all the other alleles. Chinchilla is dominant to Himalayan and white.

Multiple alleles

Multiple alleles Cross a heterozygous Chinchilla (cchc) with a heterozygous full color with himalayan (Cch). cchc x Cch

Multiple alleles cch c C ch

Multiple alleles cch c C Ccch ch

Multiple alleles cch c C Ccch Cc ch

Multiple alleles cch c C Ccch Cc ch cchch

Multiple alleles cch c C Ccch Cc ch cchch chc

Multiple alleles Genotypic Ratios: 1 Ccch: 1Cc : 1 cchch: 1 chc Phenotypic Ratios: 2 full color: 1 light grey: 1 Himalayan

Blood Genetics The human ABO gene is on chromosome 9. Everyone has two copies of chromosome 9 so you have two ABO genes. One copy is inherited from our mother, the other from our father.

Alleles There are three versions (called “alleles”) of this blood type gene: A, B, and O. A person’s blood type is determined by which allele he/she inherits from each parent.

Pheno vs. Geno The genetic makeup of an organism is called the “genotype”. The “phenotype” is the visible properties of an organism. In this case, the A, B, and O allele combination a person has is their genotype Their blood type is their phenotype.

Dominant vs. Recessive Genes The “A” allele is dominant and so is the “B” allele. Together though, the “A” and “B” alleles are co-dominant. The “O” allele is recessive.

Determining the Genotype Human blood type is controlled by three alleles : IA, IB and i. Alleles IA and IB are dominant over i IA and IB are codominant Phenotype (blood type) Genotypes A IA IA or IAi B IB IB or IBi AB IA IB O ii

Blood Types The alleles we discussed “code” for blood type. What they REALLY “code” for is a specific enzyme. That enzyme creates specific antigens on your RBC.

Antigens An antigen is a protein (encoded from the right enzyme) that “sits” on the surface of your RBC. There are 2 different blood antigens, A and B. If you have the A antigen, you have type A blood. If you have the B antigen, you have type B blood.

Antibodies Blood plasma is packed with proteins called antibodies. The body produces a wide variety of antibodies that will recognize and attack foreign molecules. A person’s plasma does not contain any antibodies that will bind to molecules that are part of his or her own body.

ABO Blood Grouping System                Blood group A If you belong to the blood group A, you have A antigens on the surface of your RBCs and B antibodies in your blood plasma.   Blood group B If you belong to the blood group B, you have B antigens on the surface of your RBCs and A antibodies in your blood plasma. ABO Blood Grouping System

Blood Groups, Blood Typing and Blood Transfusions The discovery of blood groups                       Experiments with blood transfusions, the transfer of blood or blood components into a person's blood stream, have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. Mixing blood from two individuals can lead to blood clumping or agglutination. The clumped red cells can crack and cause toxic reactions. This can have fatal consequences. Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.   What is blood made up of?                        An adult human has about 4–6 liters of blood circulating in the body. Among other things, blood transports oxygen to various parts of the body. Blood consists of several types of cells floating around in a fluid called plasma. The red blood cells contain hemoglobin, a protein that binds oxygen. Red blood cells transport oxygen to, and remove carbon dioxide from, the body tissues. The white blood cells fight infection. The platelets help the blood to clot, if you get a wound for example. The plasma contains salts and various kinds of proteins. What are the different blood groups?                                                       The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies. The antigens are located on the surface of the red blood cells and the antibodies are in the blood plasma. Individuals have different types and combinations of these molecules. The blood group you belong to depends on what you have inherited from your parents. There are more than 20 genetically determined blood group systems known today, but the AB0 and Rh systems are the most important ones used for blood transfusions. Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous or individuals. Nobel Laureate Karl Landsteiner was involved in the discovery of both the AB0 and Rh blood groups. AB0 blood grouping system                Blood group AB If you belong to the blood group AB, you have both A and B antigens on the surface of your RBCs and no A or B antibodies at all in your blood plasma. Blood group O If you belong to the blood group O (null), you have neither A or B antigens on the surface of your RBCs but you have both A and B antibodies in your blood plasma.

Blood Transfusions It is important to carefully match the donor and recipient blood types. If the donor’s blood cells have antigen that are different from those of the recipient, antibodies in the recipient’s blood recognize the donor blood as foreign. This triggers an immune response resulting in blood clotting or agglutination.

http://duongchan.files.wordpress.com/2007/05/abobloodsystem.jpg

Blood types and transfusions People who are Type A blood produce antibodies to agglutinate cells which carry Type B antigens. They recognise them as non-self The opposite is true for people who are Type B Neither of these people will agglutinate blood cells which are Type O as they do not carry any antigens for the ABO system. Type O cells pass incognito

Donor-recipient compatibility Type A B AB O Donor Note: Type O blood may be transfused into all the other types = the universal donor. Type AB blood can receive blood from all the other blood types = the universal receivers. = Agglutination = Safe transfusion

Donor-recipient compatibility                  Donor-recipient compatibility Blood group O is called "universal donor" because it has no antigens on RBC. Blood group AB are called "universal receivers” because it has no anti- bodies in the plasma.

Problem 1: Multiple Alleles Show the cross between a mother who has type O blood and a father who has type AB blood. i i GENOTYPES: IA IB IAi IBi - IAi (2) IBi (2) - ratio 1:1 PHENOTYPES: type A blood (2); type B blood(2) - ratio 1:1

Problem 2: Multiple Alleles Show the cross between a mother who is heterozygous for type B blood and a father who is heterozygous for type A blood. GENOTYPES: IA i IAIB (1); IBi (1); IAi (1); ii (1) - ratio 1:1:1:1 IB i IAIB ii IBi IAi PHENOTYPES: type AB (1); type B (1) type A (1); type O (1) - ratio 1:1:1:1

Relative Abundance of Blood Types 40-42% 10-12% 3-5% 43-45%

Rhesus Factor The Rhesus factor gets its name from experiments conducted in 1937 by scientists Karl Landsteiner and Alexander S. Weiner. Involved Rabbits which when injected with the Rhesus monkey’s red blood cells, produced an antigen present in the red blood cells of many humans

Rhesus Factor (Rh) If a person has a positive Rh factor, this means that their blood contains a protein that is also found in Rhesus monkeys.  Most people (about 85%) have a positive Rh factor Rh is expressed as either positive or negative.  The Rh factor, like other antigens, is found on the surface of the red blood cells. 

Rhesus Factor Positive (+) allele is dominant to negative (-) allele Rh +: you have the protein Rh-: you don’t Mother Father Child Rh- Rh+

Rhesus Factor If a person has either two (+) genes for Rh or one (+) and one (-) Rh gene, they will test Rh(+). A person will be negative only if they have 2 (-).

Rhesus Factor One of the basic difference between ABO and Rh systems is that the Rh antibodies are not natural i.e. they are not present at birth but are synthesised in Rh negative persons in response to the presence of Rh-antigen. Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane.

Rh Blood Group and Rh Incompatibility A person with Rh- blood does not have Rh antibodies naturally in the blood plasma Blood Type Genotype Alleles Produced Rh positive RR R Rr R or r Rh negative rr r

                                                                            A person with Rh- blood develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood. If such a person is given Rh+ blood, its anti-Rh antibodies react with the donor’s Rh antigens and aggulate the blood. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.

Why is an Rh incompatibility so dangerous when ABO incompatibility is not during pregnancy? Incompatibility is seen between Rh- woman and her foetus. Rh- woman when married to Rh+ man bears Rh+ foetus. Although the foetal and maternal blood do not come in direct contact due to placental barrier, some foetal R.B.C’s manage to enter the maternal blood stream. The Rh antigen on their surface induces formation of anti-Rh antibodies. These antibodies then cross the placenta and enter the foetus blood circulation and cause a blood disorder known as erythroblastosis foetalis. The reaction of Rh-woman against her Rh+offspring becomes progressively more severe with each subsequent pregnancy.

The “Rh Issue”… Mom = Rh- Baby #1 = Rh+

Relevance of Rh Factor & ABO Typing? It is very important in terms of babies Example: An Rh(-) mother has a Rh (+) baby, she will make antibody against the Rh(+) fetus

Rh Blood Group and Rh Incompatibility P1 : Female Rh- × Male Rh+ Baby is Rh+ because father is. Mother’s blood produces antibodies upon birth, (since blood mixes at birth). First baby is okay. Second pregnancy- mom’s antibodies can now move across the placenta and cause baby’s RBC’s to clump (agglutinate) if second baby is also Rh+. This decreases oxygen delivery in the baby – “blue baby.”

What can be done? Mom can be given an injection of a drug that inhibits antibody production immediately after delivery. What happens if this is undetected? Baby could be given a blood transfusion while in the womb. Fairly uncommon.

Blood Types & Rhesus Factor Question R – dominant allele (Rh+) r – recessive allele (Rh-) Example: A woman homozygous for blood type A and heterozygous for the rhesus allele, Rh+, has a child with a man with type O blood who is Rh-. What is the probability that their child will have blood type A, Rh+? There will be a 50% chance.

Stats O+ 1 in 3 persons O- 1 in 15 persons A+ A- 1 in 16 persons B+ AB+ 1 in 29 persons AB- 1 in 167 persons