Blood Bank Ch. 4

blood banking genetics

gene

• a segment of DNA that encodes for a particular protein

• the basic units of inheritance on a chromosome

locus

the location of a gene on a chromosome (plural: loci)

allele

• alternative forms of a gene

• A, B, and O alleles are found on the ABO gene locus

antithetical antigens

• antigens produced by opposite alleles

• examples:

  • Kp^a and Kp^b (kell) antigens

  • Lu^a and Lu^b (lutheran) antigens

Multiple alleles at a single locus are considered:

polymorphic

• the Rh blood group system is highly polymorphic

blood group system

group of antigens on the RBC membrane that share related serological properties and patterns of inheritance

What is the difference between phenotype and genotype?

• phenotype

  • the outward expression of genes, physical characteristics

  • can be determined by the agglutination of RBCs with antisera

• genotype

  • the actual genetic makeup of an individual (one gene inherited from each parent)

  • genes that code for antigens

  • determined with DNA tests and family studies

What is an amorphous gene?

a gene that does not express a detectable product

• the O gene/antigen

recessive inheritance

a gene is expressed only when inherited by both parents

• example: in order for a child to be type O blood, both parents must pass on an O allele

codominant expression

the equal expression of two different inherited alleles

• example: one parent passes on an A gene, and the other passes on a B gene, this means the child will have type AB blood

• ABO blood group inheritance is autosomal codominant

dominant expression

• only one form of an allele is required to express a trait

• one gene product is expressed over another

• example: One parent passes on an A gene and the other passes on an O gene. The child will have type A blood (A/O) because the A gene is dominant.

null phenotype

• the inheritance of silent genes (amorphs)

• blood group antigens are not expressed

• examples: Rh_null, Lu(a-b-), and group O phenotype

Most blood group system genes are present on autosomes, except for those of the ___ ___.

• XG system

  • XG genes are found on the X chromosome and are inherited in an x-linked dominant pattern

What is the difference between heterozygotes and homozygotes?

• heterozygous

  • individuals that inherit different alleles from their parents

  • ex: genotypes AO, BO, and AB

• homozygous

  • individuals that inherit identical alleles from their parents

  • ex: AA, BB, or OO

What is the dosage effect?

• a phenomenon where an antibody reacts more strongly with an RBC carrying a double dose than an RBC carrying a single dose of an antigen

  • double dose: red cells with homozygous antigens

  • single dose: red cells with heterozygous antigens

• can be the reason for agglutination reactions varying in strength (double dose RBCs show stronger reactions that single dose RBCs)

• example: an individual that inherits the alleles MM (M+N-) has double dose expression, and an individual that inherits the alleles MN (M+N+) has a single does expression

What is a haplotype?

• a linked set of genes that are inherited together because of their close proximity on a chromosome

• example: In the MNSs blood group, M and N are alleles on one gene, and S and s are alleles on another gene. These alleles can be inherited as a haplotype as MS, Ms, NS, or Ns.

What are population genetics?

• the application of genetic principles to calculate blood group genotype and phenotype occurrence in an area

What is the purpose of the phenotype calculation?

• used when finding a unit of RBCs with certain antigen characteristics

• useful for patients who need a transfusion but have several red cell antibodies

  • reduces the delay in providing units and is more cost efficient

• calculation uses the estimated genotype and phenotype percentages from the general population

How do you do a phenotype calculation?

1. Given the antigen frequency for each antibody the patient has, find the negative frequency

2. Convert the negative frequencies to decimals and multiply them

3. IF QUESTION LISTS THE AMOUNT OF UNITS NEEDED: divide the number of units needed by the antigen negative frequency

What are the applications of molecular genetics to blood banking?

• organ transplantation

• transfusions

• donor testing

• detecting HDFN

What is PCR and how does it work?

• molecular testing method that rapidly and precisely multiplies DNA segments for identification

• steps:

  • DNA is denatured

  • a primer is added and attaches to a specific area of DNA

  • primer undergoes extension to create a complementary strand of DNA (DNA is multiplied exponentially)

List 4 types of HLA typing methods with PCR

• sequence-specific primers (SSPs)

• sequence-specific oligonucleotides (SSOs)

• sequence-based typing (SBT)

• short tandem repeats (STRs)

independent segregation

the passing of one gene from each parent to offspring

independent assortment

random behavior of genes on separate chromosomes during meiosis that results in a mixture of genetic material in the offspring

DNA probe

a short sequence of DNA complementary to the target area and attached to a marker (usually fluorescent) read by an instrument, such as a flow cytometer

With which of the following red cell phenotypes would anti-Jka react most strongly?

• Jk(a-b+)

• Jk(a+b-)

• Jk(a+b+)

• Jk(a-b-)

Jk(a+b-)

List 3 situations where molecular red cell antigen typing would be useful

• solving ABO discrepancy

• screening RBC inventory for antigen-negative units

• resolving a weak D phenotype