3. Concepts of Genetics and Inheritance in Transfusion Science

What are alternate forms of a gene present at the same locus on a chromosome called?

Alleles

What concept is shown in this diagram regarding gene variations at a specific chromosome locus?

A gene locus containing alleles or gene variations, such as $A$, $B$, or $O$ in the ABO blood group system.

What term describes having identical allelic genes at a given locus versus having different allelic genes?

Homozygous describes identical alleles (e.g., $KK$, $CC$), while heterozygous describes different alleles (e.g., $Kk$, $Cc$).

What genetic state is illustrated in this diagram comparing chromosome pairs?

Homozygous ($M M$) on the left versus Heterozygous ($M N$) on the right.

What is the genome?

The full complement of genes in an organism.

What does polymorphic mean in blood group genetics?

Having $2$ or more alleles at a given locus (e.g., the Rh system).

What does antithetical mean in blood group antigen terminology?

Opposite antigens encoded at the same locus (e.g., $Fy^a$ is antithetical to $Fy^b$, or $K$ is antithetical to $k$).

How are most red blood cell antigens inherited and expressed?

Co-dominantly, meaning both inherited alleles are expressed equally on the red blood cells.

What is Mendel's Law of Independent Segregation?

The passing of one gene from each parent to the offspring.

What is Mendel's Law of Independent Assortment?

The random behavior of genes on separate chromosomes during meiosis, resulting in a mixture of genetic material in the offspring.

What is the dosage effect in blood group testing?

A phenomenon where an antigen demonstrates stronger agglutination when expressed homozygously (double dose) than when expressed heterozygously (single dose).

How does anti-M reaction strength differ between homozygous ($R1R1$) and heterozygous ($R2R2$) cells in this panel?

Homozygous $M+N-$ cells ($R1R1$) show a stronger reaction ($3+$) than heterozygous $M+N+$ cells ($R2R2$) ($1+$) due to dosage effect.

Which blood group systems and antigens demonstrate dosage effect?

Duffy ($Fy^a$, $Fy^b$), Rh (except D; specifically $C$, $c$, $E$, $e$), MNSs, and Kidd ($Jk^a$, $Jk^b$).

What is genetic linkage, and how does it affect independent assortment?

Linkage occurs when genes are located very close together on the same chromosome and are inherited together as a unit; independent assortment does not occur when genes are linked.

What is genetic crossing over?

The exchange of genetic material between paired chromosomes during meiosis, which occurs less frequently when genes are close together.

What is a haplotype?

A unit of genes located very close together on a chromosome that are inherited together as a unit from a parent (e.g., $MS$, $Ms$, $NS$, or $Ns$).

What are the three loci in the Fisher-Race genetic theory for the Rh blood group system?

$D$ or $d$; $C$, $c$, or $C^w$; and $E$ or $e$.

What is the phenotype and genotype shown in this MNSs haplotype diagram?

Phenotype: MNSs; Genotype: $MS, Ns$.

What are the most frequently inherited Rh positive and Rh negative haplotypes?

The most frequent Rh positive haplotype is $CDe$; the most frequent Rh negative haplotype is $cde$ (or $ce$), where $d$ is an amorph.

What is an amorph (silent gene) and what phenotype does it produce when homozygous?

An amorph is a gene with no detectable antigen product; inheriting it from both parents results in a "NULL" phenotype (e.g., $Rh_{null}$).

What is a suppressor gene and what are two examples in blood group systems?

A suppressor gene suppresses the expression of another gene to produce a NULL phenotype. Examples include $In(Jk)$ producing $Jk(a-b-)$ and $In(Lu)$ producing $Lu(a-b-)$.

What is the difference between cis and trans gene positioning?

Cis means genes are on the same chromosome; trans means genes are on opposite homologous chromosomes.

What is the difference between D and C in cis versus D and C in trans?

In cis, $D$ and $C$ are inherited on the same chromosome ($DC/dc$); in trans, $D$ and $C$ are inherited on opposite chromosomes ($Dc/dC$).

How does inheriting C in trans to D affect D antigen expression?

It may weaken the $D$ antigen expression on the red blood cells.

What is an obligatory gene in relationship/paternity testing?

A gene that SHOULD be passed on by the alleged father to prove or disprove paternity.

What is a direct exclusion in paternity testing?

A genetic marker inherited by the child that is NOT found in either the mother or the alleged father.

What is an indirect exclusion in paternity testing, and why is it insufficient on its own?

It occurs when a child lacks a genetic marker that should have been inherited; it cannot be used alone because the absence may be due to a silent gene.

How is phenotype frequency determined for a blood group antigen?

By testing red cells from a large random sample of individuals of the same race and calculating the percentages of positive and negative results.

If $900$ out of $10{,}000$ Caucasians test positive for the Kell antigen, what are the Kell positive and Kell negative phenotype frequencies?

Kell positive frequency is $9\text{\%}$, and Kell negative frequency is $91\text{\%}$.

According to the antigen frequency chart, what are the population frequencies for antigens e, k, and Kpb?

$e = 98\text{\%}$, $k = 99.9\text{\%}$, and $Kp^b = 99.9\text{\%}$.

What is the percent negative frequency for a combination of antigens E (30% pos), c (80% pos), and Fya (65% pos)?

$4.9\text{\%}$ ($0.70 \times 0.20 \times 0.35 \times 100 = 4.9\text{\%}$).

How many units of blood must be screened to find 2 compatible units negative for E, c, and Fya (4.9% negative frequency)?

$40$ units ($\frac{5}{100} = \frac{2}{x} \rightarrow x = 40$).

How many units of blood must be screened to find 4 units negative for K (9% pos), c (80% pos), and Jka (77% pos)?

$100$ units (Negative likelihood = $0.91 \times 0.20 \times 0.23 \times 100 = 4.1\text{\%}$; $\frac{4}{100} = \frac{4}{x} \rightarrow x = 100$).

What type of cell is chosen as a positive control when testing for blood group antigens?

A heterozygous cell (single dose) for the appropriate antigen (e.g., $E+e+$, $C+c+$, $Fy^a+Fy^b+$).

What type of cell is chosen as a negative control when testing for blood group antigens?

A cell negative for the appropriate antigen (e.g., $E\text{ neg}$, $c\text{ neg}$, $Fy^a\text{ neg}$).