Human Genetic Variation Flashcards
Give some applications for human genetics
Cancer prognosis and treatment Antenatal diagnosis Parentage Body identification Forensics Genetic counselling
Which blood type is the “universal donor” and why?
Type O
Because there are no antigens on the surface of RBCs, so nothing to have an antibody against.
Which blood type is the universal recipient and why?
Type AB
Because it has antigens A and B so cannot develop antibodies for either; therefore can accept RBCs from any other type.
Describe and explain the difference between serum donation and blood transfusion
The universal donor and recipient blood types are reversed. This is because antigens for A and B types reside in the serum. Only blood types without A and B antigens present can develop antibodies against them, so the AB type serum contains no antibodies, and is compatible with any other blood type. The O type serum, on the other hand, can have antibodies against both A and B, so can only be given to other O types.
What do the ABO blood types actually represent?
Encode post-translational modifications for antigens on the RBC.
Allele A gives a phenotype where N-acetylgalactosamine is present on the cell surface.
Allele B gives a phenotype where ga;actose is present on the RBC surface.
Allele O encodes no additions, leading us to the conclusion that the ABO locus also encodes for the enzyme which causes these modifications, glycosyltransferase.
What mutations occurred to cause ABO blood groups?
B developed from 4 amino acid substitutions.
O develop developed as a result of a single base pair deletion, leading to a frameshift, which explains why no modifications are present on this cell type.
What is the basis of rhesus blood typing?
The presence or absence of the D antigen on the surface of RBCs.
Describe how haemolytic disease of the newborn occurs
It occurs when a mother is rhesus negative and gives birth to her second rhesus positive child. She would have developed antibodies against rhesus positivity after exposure to the blood of her first rhesus positive child. These antibodies would have passed into the blood of her subsequent children and caused haemagglutination in the child.
How can the child of a rhesus negative mother be rhesus positive?
The D allele is autosomal dominant so if the father is Rh+, the child could be. If he’s heterozygous, 50% of their children will be Rh+, whereas if he’s homozygous, all of their children will be Rh+
How many alleles are there for the rhesus gene and what does each cause?
There are over 50, though the following are most important;
D = Rh+
d = Rh- and is due due to a deletion of D
C/c and E/e cause alternative splicing, 4 amino acids and 1 amino acid respectively. E and C are also usually inherited together.
What are the pros and cons of using protein electrophoresis to detect polymorphisms
Pros;
Simple, cheap
Cons;
Underestimates the extent of genetic variation as some mutations cause little change in mass and charge, so would not appear different on electrophoresis. Also can’t be used for null alleles.
What is Restriction Fragment Length Polymorphism RFLP?
A difference in DNA that results in different gene product mass or charge. This is detected by protein electrophoresis.
What are the pros and cons RFLP?
Pros; can look at specific interesting proteins
Cons; poor sensitivity (need a microgram of DNA aka 0.1 ml of blood); Is restriction enzyme dependent; Many variants undetectable.
What are VNTRs?
Variable number tandem repeat loci.
These are usually hundreds of base pairs long. There are 1000s in the genome, and they have a GC rich sequence. They are also highly variable and polymorphic.
What are STRs?
Short tandem repeat loci.
These are usually tens to one hundred base pairs long and are therefore amplifiable by PCR. There are around 50000 loci in the genome, and are very dispersed (eg one per 10kb)
