Basic Blood Bank Genetics Flashcards
How does genetics influence blood groups?
- Different genes produce enzymes that add different types of sugars (ABO/ Lewis)
- Different genes produce proteins which are found on the surface of RBC (Duffy system)
Gene
a unit of heredity which is transferred from a parent to offspring and is held to determine some characteristic of the offspring
Allele
one or two more alternative forms of a gene (one from mom and one from dad)
Homozygous
Having two identical alleles of a particular gene or genes
Heterozygous
Having two different alleles of a particular gene or genes
Genotype
-the genetic composition of an individual organism
Phenotype
-the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment
Penetrance
the extent to which a particular gene or set of genes is expressed in the phenotypes of individuals carrying it
-measured in the proportion of carriers showing the characteristic phenotype
Gene modifiers
-elements which affect the phenotypic and or molecular expression of other genes
polymorphic
variants of a particular DNA sequence
-used in the setting of Rh blood groups
haplotype
set of DNA variations, or polymorphisms, that tend to be inherited together
-used in the setting of Rh blood groups
Cis
-when alleles occupy adjacent loci on the same chromosome
Trans
-when alleles occupy adjacent loci on different chromosomes
Mendel’s first law
shows that alleles of genes have no permanent effect on one another when present in the same plant but segregate unchanged by passing into different gametes
Law of segregation (1st law)
-a diploid individual possesses a pair of alleles for any particular trait and each parent passes one of these randomly to its offspring
autosomal dominant
-inheritance of dominant allele results in its phenotypic expression over a recessive allele
autosomal co-dominant
-inheritance of two different alleles which results in the phenotypic expression of both alleles or partial expression of one allele
autosomal recessive
-inheritance of two copies of a recessive allele or one amorph is required for the phenotypic expression of the allele
Amorph
-mutated allele that has lost the ability to encode any functional protein
Dominant (sex-linked)
-inheritance of the allele on the X or Y chromosomes results in full expression of the phenotype
Co-dominant (sex-linked)
-inheritance of two different alleles on an X chromosome results in the phenotypic expression of both the alleles or partial expression of one allele
Recessive (sex-linked)
-inheritance of the allele on the X chromosome resulting in all-male offspring expressing the trait and no females
-or the trait is expressed in all males inheriting the affected X chromosome or females inheriting two X chromosomes with the allele
Codominance
-both alleles are expressed and their gene products are seen at the phenotypic level
-The homozygous type would have a stronger reaction than the heterozygous
Dosage
significant difference in antibody reaction strength depending on the quantity of the target
-JKa JKb antigens will have a decreased quantity of each (single dose)
-JKa JKa antigens will have higher quantity and react stronger (double dose)
Examples that show dosage
-Duffy
-Kidd
-Rh
-MNSs blood group systems
Mendel’s second law (Law of independent assortment)
- genes for different traits are inherited separately from each other
- This allows for a possible combination of genes to occur in the offspring
- Mendel’s law applies to all sexually reproducing diploid organisms
Exceptions to Mendel’s second law
- if genes for separate traits are closely linked on a chromosome they can be inherited together as a single unit
Hardy-Weinberg Equation
p2+2pq+q2 = 1
-describes an idealized state
p = frequency of allele 1
q = frequency of allele 2
What are the criteria that must be met in order to use the Hardy-Weinburg?
- The population studied must be large
- Mating must be random
- No mutations in parents or offspring
- No migration, no differential fertility, and no mortality of genotypes studied
Phenotype frequencies
- found by random testing of a population
- independent phenotypes may be multiplied to give the frequency of the combinations in a population or the lack of the combination phenotype in the population
Pedigree analysis
requires the understanding of various standard conventions in the representation of data figures
-males = squares
-females = circles
-Line joining a male and female indicates mating
-offsprings are indicated by a vertical line
- consanguineous mating is indicated by a double line
Propositus
-the most interesting member of the pedigree indicated by an arrow
Is inclusion certain
-never (but with genetic molecular testing it can be pretty close to certainly)
is exclusion certain
-can be pretty certain in some circumstances but mutation is always a possibility
Direct exclusion
when a genetic marker is present in the child but absent from both the mother and the alleged father
Indirect exclusion
when a genetic marker is/are absent from the child that should have been transmitted by the alleged father given his observed phenotype
What are the criteria for suitable markers?
- well-established inheritance patterns
- reliable phenotype determination
- unhindered expression of the gene (co-dominant without modifier gene or null gene)
- high frequency of common alleles
- able to generate good probability of exclusion
- many alternative alleles
- gene frequencies established in the population in question
Examples of suitable markers
ABO, Rh, MNSs, Kidd, Kell, Duffy, HLA, serum proteins, plasminogen, haptoglobin, transferrin, properdin B
RFLP
restriction fragment length polymorphisms
-very robust system when used with at least 4 probes
-multiple probes and restriction endonucleases required as mutation is common and fragment length varies on both ends
PCR
-used with HLA markers and VNTR and short tandem repeats
-pretty much the standard these days with 99% inclusion and 100% exclusion
-can now be done with pregnant women’s blood utilizing circulating fetal DNA
