Chapter 4 Genetic Principles in Blood Banking

Question 1

What is a phenotype?

Answer 1

Physical (observed) expression of traits.

In the blood bank, the patient’s phenotype is determined by hemagglutination of RBC antigens using antisera.

Question 2

What is a genotype?

Answer 2

It is the actual genetic makeup and can only be determined by molecular techniques or family studies.

Question 3

Can a pedigree chart help determine genotype?

Answer 3

Yes. A person with phenotype A could have genotype A/A or A/O; family studies can determine which is present.

Question 4

What is a Punnett’s square used for?

Answer 4

A Punnett square is used to predict the probability of an offspring’s genotype. It summarizes every possible combination of maternal and paternal alleles of a particular gene.

Question 5

What is a locus on a gene?

Answer 5

A locus is the site at which a gene is located on a chromosome; e.g. ABO genes are on chromosome 9.

Question 6

What are alleles?

Answer 6

Alleles are alternative forms of a gene found at a locus.

Antigens produced by opposite alleles are antithetical (e.g., Kpa and Kpb antigens)

Question 7

What kind of matching is required for bone marrow and organ transplants? Why?

Answer 7

Bone marrow and organ transplants required HLA matching because the HLA it is quite polymorphic.

Polymorphic means multiple alleles at a single locus.

Question 8

What does codominant mean?

Answer 8

Equal expression of two different alleles. Blood group antigens are codominant. E.g. AB type.

Question 9

What does dominant mean?

Answer 9

Gene that is expressed over another.

Question 10

What does it mean when a gene is recessive?

Answer 10

Gene is expressed only when inherited by both parents.

Question 11

What are amorphic genes?

Answer 11

Genes that do not express a detectable product (“silent genes”) are considered amorphic (e.g. O gene).

Question 12

What does it mean when genes are independent segregation?

Answer 12

Independent segregation occurs when one gene from each parent is passed to the offspring
o E.g., ABO Punnett square exercise

Question 13

What does it mean when independent assortment is demonstrated?

Answer 13

Independent assortment is demonstrated when blood group antigens from different chromosomes are expressed separately, resulting in a mixture of genetic material
o ABO and Kell blood group antigens are inherited independent of each other
o 2 exceptions to this law are linkage and crossing over

Question 14

What is it called when 2 genes are close to each other and inherited together?

Answer 14

Linkage
- too close for independent assortment
- each set of linked genes is called a HAPLOTYPE.

Question 15

What is linkage disequilibrium?

Answer 15

Haplotypes tend to occur at a higher frequency than for unlinked genes, a phenomenon called linkage disequilibrium.

Question 16

What is the difference between inherited genes that are in cis versus trans position

Answer 16

The location of inherited genes in cis or trans positions can affect the expression of the antigen
o Alleles on the same chromosome are cis to one another
o Alleles on opposite chromosomes are in the trans position
E.g. When Ce is inherited in trans to D, it weakens D antigen expression

Question 17

What is the difference between heterozygosity and homozygosity?

Answer 17

• A person who inherits identical alleles is called homozygous AA, BB, MM (M+ N–)
• A person who inherits different alleles is called heterozygous AO, AB, MN (M+ N+)

Question 18

Why is it important to know heterozygosity vs homozygosity in the blood bank?

Answer 18

It is important to know this. When we select controls for phenotyping we want to find panel cells that are heterozygous for the allele we are testing for (antisera we are using). We want to prove that we will detect it, even its it’s weakest form. This is important if the blood group system shows dosage.

Question 19

What is the dosage effect with blood group antigens?

Answer 19

Dosage is a variation in antigen expression due to the number of alleles present
• Not seen with ABO
•In some blood group systems, persons homozygous for an allele have a “double dose” of an antigen on their RBCs compared with those who are heterozygous for an allele
• Homozygous expression of some antigens will show stronger agglutination compared with antigens that are heterozygous

Question 20

What two formulas are used to determine genotype or phenotype occurrence?

Answer 20

To determine genotype or phenotype occurrence, two formulas are used:
o A phenotype calculation enables finding a unit of RBCs with certain antigen characteristics (i.e., antigen negative)
o The Hardy-Weinberg formula calculates a determination of the gene frequencies that produced a trait

Question 21

What are some applications that used molecular genetics in transplantation?

Answer 21

Transplantation
1. HLA antigen-level and allele-level typing for HPC and organ transplants.
2. Engraftment studies for HPC transplants.

Question 22

What are some applications for transfusion that used molecular testing in the blood bank?

Answer 22

Transfusion - molecular testing in the blood bank
1. Red cell typing in multiply transfused patients
2. Determine blood type when the DAT is positive.
3. Complex Rh genotypes, weak D expression.
4. Screen for antigen-negative donor units when antisera are unavailable.
5. Donor antigen screening for prevention of alloimmunization.

Question 23

What are molecular applications for HDFN, donor testing and relationship testing?

Answer 23

HDFN
1. Determine parental RhD zygosity
2. Type fetal blood
Donor Testing
1. Detect virus in donors that may be below detectable levels by antibody detection methods.
Relationship Testing
1. Establish paternity and legal relationships for immigration.