Chapter 4 - Genetic Principles in Blood Banking

Blood Group Systems

groups of antigens on the RBC membrane that share related serologic properties and genetic patterns of inheritance

• composed of antigens that are produced by alleles at a single gene loci

• ex = ABO, Rh, Lewis, Kidd, Duffy, MNS, Lutheran

ABO antigens

A, B

Rh antigens

D, C, c, E, e

Lewis antigens

Le^a, Le^b

Kidd antigens

Jk^a, Jk^b

Duffy antigens

Fy^a, Fy^b

MNS

M, N, S, s

Lutheran

Lu^a, Lu^b

Blood group systems Ag characteristics

structure and location on RBCs

antibodies that they elicit

• develop Ab to the Ag you lack if exposed

genetic control of expression

classified as:

• proteins

• carbohydrates linked to a lipid or a protein

Blood group genetics

genetic material found in DNA

DNA is contained in chromosomes that are in the nucleus of every cell

genetic material is replicated either by mitosis (somatic cells) or meiosis (gametes)

Phenotype vs. Genotype

Phenotype

• physically (observed) expression of traits

• the patient’s phenotype is determined by hemagglutination of RBC antigens using antisera

• Ex. a person who shows no agglutination with anti-A or anti-B antisera is considered to have type O blood

Genotype

• actual genetic makeup

• can only be determined by molecular techniques or family studies

• Ex. a person with phenotype A could have the genotype A/A or A/O; family studies would be necessary to confirm which is present

Punnett Square

used to predict probability of an offspring’s genotype

summarizes every possible combination of maternal and paternal alleles of a particular gene

Genes

basic units of inheritance on a chromosome

locus is the site at which a gene is located on a chromosome

alleles, which are alternative forms of a gene, are found at each locus

• Ags produced by opposite alleles are antithetical (Kp^a, Kp^b antigens)

• multiple alleles at a single locus are considered polymorphic (Rh system)

  • 2 or more alleles at same gene locus

Inheritance

Recessive = gene expressed only when inherited by both parents

Codominant = equal expression of two different alleles, blood group antigens

Dominant = gene that is expressed over another gene

Amorphic genes

genes that do not express a detectable product

ex = O blood gene

amorphic gene results in a ___ genotype and a ___ phenotype

amorphic genotype

null phenotype

• Jk^a - and Jk^b -

Mendelian principles

independent segregation occurs when one gene from each parent is passed to the offspring

independent assortment is demonstrated when blood group antigens from different chromosomes are expressed separately resulting in a mixture of genetic material

• two exceptions = linkage and crossing over

Linkage

occurs when 2 genes that are close to each other are inherited together

• each set of linked genes is called a haplotype

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

• independent assortment does not occur

Crossing over

occurs when 2 genes on the same chromosome combine and produce 2 new chromosomes

• rarely occurs in blood group systems because they are so close or on different chromosomes

Chromosomal Assignment

most blood group system genes are on autosomes, except for those of the Xg system

Xg genes are found in the X chromosome

• if father carries Xg allele, he will pass it to all of his daughters but not to any of his sons

• if mother carries Xg allele, all of their children will express Xg

Heterozygosity and Homozygosity

a person who inherits identical alleles is called homozygous

• stronger reactions

• AA, BB

a person who inherits different alleles is called heterozygous

• AO, AB

Dosage

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

dosage is a variation in antigen expression due to the # of alleles present

• MNS, Duffy, (some) Rh

Homozygous expression of some antigens will show ____ agglutination compared with antigens that are heterozygous

stronger

Genetic interaction

the location of inherited genes in cis or trans positions can affect the expression of the antigen

• alleles on the same chromosome are cis to one another

  • expression on RBCs strengthen

• alleles on opposite chromosomes are in the trans position

  • expression on RBCs weaken

Population genetics

to determine a genotype or phenotype occurrence, two formulas are used:

• phenotype calculation = enables finding a unit of RBCs with certain antigen characteristics

• Hardy-Weinberg formula = calculates a determination of the gene frequencies that produced a trait

Relationship testing

if maternity is assumed, paternity can be excluded by either indirect or direct exclusion

• direct = child inherits a genetic marker that is not found in mother or alleged father

• indirect = child lacks a genetic marker that the father should have transmitted to all offspring

  • obligatory gene, gene that should be inherited from father to prove paternity

*Phenotype calculations

patient with multiple antibodies (anti-C, anti-E, anti-S needs blood)

70% C positive - 30% - 0.30

30% E positive - 70% neg - 0.70

55% S positive - 45% neg - 0.45

0.30 × 0.70 × 0.45 = 0.10 (10%)

Hardy-Weinberg Formula

gene frequency: p + q = 1

p = allele #1

q = allele #2

what is the frequency of q if p = 0.3

0.3 + q = 1

q = 0.7 or 70%

genotype proportions: ( p² + 2pq + q² = 1.0 )

0.9 (AA) + 0.42 (Aa) + 0.49 (aa) = 1.0

Molecular Genetics Applications (table 4.3)

Applications of Molecular Testing in the Blood Bank

Transplantation

• HLA antigen-level and allele-level typing for HPC and organ transplants

Transfusion

• red cell typing in multiply transfused patients

HDFN

• determine parental RhD zygosity

• type fetal blood

Donor testing

• detect virus in donors that may be below detectable levels by anti-body detection methods

Relationship testing

• establish paternity and legal relationships for immigration