Genetic Variations in Individuals and Populations Flashcards
What is the difference between a genome mutation and a chromosome mutation?
Genome mutations involve chromosome misaggragation (for example: Aneuploidy) resulting in abnormal numbers of chromosomes
Chromosome mutations are smaller scale mutations due to errors in rearangements (for example: translocation)
Translate m.8393C>T into laymans terms
A point mutation on mitochondrial DNA base number 8393 occured in which a C was converted into a T
Translate c.1257_1261delACGTC into layman’s terms
A deletion of bases 1257 to 1261 (sequence: ACGTC) occured on cDNA
What does IVS stand for ?
Intervening sequence
What parameters impact the likelihood that a germline mutation will occur?
Gene size (larger genes, greater risk)
Presence of CG sequences
Mutation phenotype
Parental age
Parental gender
Why is there an increased risk for nondisjunction in the germline with age of a female?
The oocytes are sitting from puberty until fertilization, so with more time there is a greater risk for an abnormal crossing over event to occur.
Which meiotic division contributes a greater percentage of the total germline mutations in females?
The first meiotic division
Nondisjunction during meiosis I results in 4 gametes with abnormal number of chromosomes (2 with n+1 and 2 with n-1)
What type of mutation is most common in male germline production?
Replication errors
What are polymorphisms?
Variant sequences that occur in more than 1% of the population
What is the difference btween a STRP indel and a VNTR indel?
STRP indel = short tandem repeat polymorphism, 5-25 copies of a 2-3 nucleotide repeat
VNTR indel = variable number tandem repeat sequence, up to 1000s of copies of a 10-100 nucleotide tandem repeat
What are microsatellites and why are they useful for identifying individuals?
Microsatellite markers are stretches of DNA containing tandem repeats of 2, 3, or 4 (STRPs)
Different people have different number of repeats, so they can be used for forensic purposes
What are minisatellites?
Multiple copies of DNA sequences of 10-100 basepairs present in tandem
Larger segments than microsatellites. Difficult to detect with PCR.
What are the different possible blood types?
O, A, B and AB
How do the sugars attached to galactose in the H-protein oligosaccharide differ between blood types?
O: none
A: N-acetylgalactosamine
B: Galactose
AB: both types are present
How do antibodies in serum differ between individuals with different blood types?
O type: anti-A and anti-B
A type: anti-B
B type: anti-A
AB: no antibodies
Which blood type is considered universal donors? Universal recipients?
O is universal donors (no sugars present)
AB is universal recipients (no antibodies present)
What is the rhesus factor?
RhD is found on the surface of red blood cells
Mutations are inherited as an autosomal recessive trait
Rh+ individuals do have the D antigen on their RBCs, wheras Rh- individuals do not.
Rh- individuals have antibodies agains Rh+ red blood cells, which can be problematic in Rh- mothers carrying Rh+ children
Where are the MHC genes found?
In a gene rich region on chromosome 6p
Why is the variability in the MHC gene problematic for transplantation?
Because there are so many different possible genes, it is very difficult to find a match between donor and recipient
What is the role of MHC class I?
It presents intracellular proteins including viral proteins
These proteins are degraded and presented to HLA I molecules in the endoplasmic reticulum, they are then expresed on the cell surface and if the presented protein is considered foreign, an immune response would be triggered
What is the role of MHC class II?
Extracellular proteins and bacteria can be taken up and presented on MHC class II
Professional antigen presenting cells express MHC II on their surface, help immune system to detect when foreign protein is present extracellularly
What is a haplotype?
A group of alleles in coupling at closely linked loci that are inherited as a unit
Because of the proximity of genes, there is a very low chance that a cross over event will separate them.
Example: MHC genes
What are the odds that a sibling will inherit the same two copies of MHC genes?
1/4
Simple mendellian genetics, group of MHC genes are inherited as a haplotype
What is the Hardy-Weinberg equilibrium equation?
Estimates the genotype frequencies from allele frequencies and vice versa
p2 + 2pq + q2 = 1
Assuming brown eyes are dominant over blue eyes, in a population of 200 people, 168 have brown eyes.
What is the value of p? q?
Blue eyed people are homozygous recessive (q2), q = sqrt((200-168)/200) = sqrt(0.16) = 0.4
p+q = 1, so p = 0.6
For an X-linked disease, how is the incidence of disase among males calculated?
The incidence of disease among males equals q because males only have 1 X chromosome
Males with the gene will all have the disease
What are the exceptions to the Hardy-Weinberg equilibrium?
Genetic drift
Founder effect
Reduced fitness
What are the assumptions for meeting Hardy-Weinberg equilibrium?
Large population: not influenced by chance fluctuations
Random mating: no preference based on phenotype similarities
No mutation: no conversion of P allele to Q allele
No selection: all genotypes are equally capable of mating and producing offspring
What can compensate for reduced fitness to lead to population equilibrium?
The new mutation rate can compensate for reduced fitness
M=sq, where M=mutation rate, s= selection coefficient = 1-f
