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.

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.

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

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

Multiple alleles

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.

               Blood group AIf 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 BIf 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 group ABIf 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 OIf 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

Recipient

Type A B AB O

A

Donor B

AB

O

= Agglutination

= Safe transfusion

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.

              

 

• 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.

Donor-recipient compatibility

Problem 1: Multiple Alleles

Show the cross between a mother who has type O blood and a father who has type AB blood.

- IAi (2) IBi (2)- ratio 1:1

- type A blood (2); type B blood(2)- ratio 1:1

GENOTYPES:

PHENOTYPES:

i i

IA

IB

IAi

IBi

IAi

IBi

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.

-IAIB (1); IBi (1); IAi (1); ii (1)- ratio 1:1:1:1

-type AB (1); type B (1) type A (1); type O (1)- ratio 1:1:1:1

GENOTYPES:

PHENOTYPES:

IA i

IB

i

IAIB

ii

IBi

IAi

Relative Abundance of Blood Types

A B AB O

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. 

Mother Father Child

Rh- Rh+ Rh+

Rh- Rh- Rh-

•Positive (+) allele is dominant to negative (-) allele

•Rh +: you have the protein Rh-: you don’t

Rhesus Factor

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 (-).

• 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.

Rhesus Factor

BloodType

GenotypeAllelesProduced

Rh positiveRR R

Rr R or r

Rh negative rr r

Rh Blood Group and Rh Incompatibility

A person with Rh- blood does not have Rh antibodies naturally in the blood plasma

                                                                           

• 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+

It is very important in terms of babies Example: An Rh(-) mother has a Rh (+) baby, she

will make antibody against the Rh(+) fetus

Relevance of Rh Factor & ABO Typing?

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.”

Rh Blood Group and Rh Incompatibility

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+ 1 in 3 persons

A- 1 in 16 persons

B+ 1 in 12 persons

B- 1 in 67 persons

AB+ 1 in 29 persons

AB- 1 in 167 persons