8.23.16 Lecture Flashcards
Genetic variation defines ___ (phenotypic variation) and ethnic differences, provides us with markers of ___, and defines susceptibility to disease.
Inter-individual differences; disease
What is the general format of mutation notation?
Type of sequence, nucleotide number, nucleotide, > replacement nucleotide
What are the abbreviations for the 5 types of sequence?
g: genomic
c: cDNA
m: mitochondrial
r: RNA
p: protein
The nucleotide is capitalized for which type of sequence? Lowercase for which type of sequence?
Genomic; RNA
In introns, a mutation is noted as ___#, where the donor splice site G is assigned position ___.
IVS (Intervening Sequence); +1
How are deletions and insertions notated?
By start and stop nucleotide # separated by _ then del or ins followed by affected nucleotides
How are translated mutant sequences notated?
Original aa in 3 letter code, position in protein, replacement aa or X for stop codon
What are polymorphisms?
Variant sequences (not necessarily deleterious) occurring at an allele frequency >1%
What are the 5 types of typical polymorphisms?
- Single nucleotide polymorphisms (SNP; 2 alleles)
- Simple insertions or deletions (indols; 2 alleles)
- Short tandem repeat sequences (STRP; 5+ alleles)
- Variable number tandem repeat sequences (VNTR; 5+ alleles)
- Copy number polymorphisms (CNP; 2 alleles)
What are three examples of polymorphisms?
ABO, Rh, and MHC
How are ABO blood groups defined?
By glycosyltransferase that adds either N-acetylgalactosamine residues (A) or D-galactose residues (B) or no sugars (O) to the H-antigen on RBC.
What are the phenotypes, attached sugars, inheritances modes, and antibodies in serum for the 4 blood groups?
O - no sugar - recessive inheritance - anti-A, anti-B
A - N-acetylgalactosamine - dominant inheritance, anti-B
B - galactose - dominant inheritance, anti-A
AB - both types of sugar - co-dominant inheritance - neither
What is the universal blood donor?
O
What is the universal blood recipient?
AB
The Rhesus factor, expressed on RBC, is encoded on chromosome ___. Mutations are inherited ___.
1; autosomal recessive
What are the two Rhesus phenotypes, the corresponding presence of Rh-D polypeptide on RBC surface, mode of inheritance, and antibodies Rh-D in serum?
Rh negative - Rh-D polypeptide absent - recessive inheritance - antibodies to Rh-D present
Rh positive - Rh-D polypeptide present - dominant inheritance - antibodies to Rh-D absent
What are MHC class I and class II and what do they do?
Major histocompatibility complexes; define expression of human lymphocyte antigen (HLA) needed to present antigen to specific T-cells.
MHC complexes are encoded on which chromosome?
6p
Matching ___ is pivotal for transplants.
HLA
The MHC cluster is inherited as a haplotype - what does this mean?
These genes are mapped in close proximity to another another and are thus inherited together; very dense part of the genome, highly polymorphic, many alleles
Disregarding crossing over, siblings have a ___ chance of sharing both alleles of the MHC haplotype.
25%
Knowing ___ and ___ frequencies in a population allows us to calculate risk.
Genotype; allele
What does the Hardy-Weinberg equilibrium do?
Describe the relationship between allelic frequencies and genotype frequencies in a stable population
What is the Hardy-Weinberg equilibrium equation?
(p+q)^2 = p^2 + 2pq + q^2; p and q must remain constant, p + q = 1
What is the Hardy-Weinberg equilibrium equation for 3 possible alleles?
(p+q+r)^2
Disease frequency = ?
q^2
How does the Hardy-Weinberg equilibrium change for sex-linked diseases?
Genotype frequency = allele frequency in males
What are the 4 conditions necessary for 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/producing offspring)
Generally, random mating means what 3 things?
- No stratification (subpopulation exists that remains genetically separate)
- No assortative mating (choice of mate determined by common trait)
- No consanguinity
What are the three major exceptions to Hardy-Weinberg equilibrium?
- Gene flow: slow movement of genes between populations
- Genetic drift: chance changes with the environment favoring a genetically defined subpopulation
- Founder effect: small population with different allele frequency breaks away from general popualtion
What is fitness?
Ability to procreate
Reduced fitness occurs in conditions that affect the ability of diseased individuals to ___.
Procreate
f (fitness) usually = ___ in dominant disease
For a population in equilibrium, the new mutation rate (mu) = ?
sq; s (selection coefficient selection against mutation) = 1-f
What is positive selection of heterozygotes?
In a balanced polymorphism, forces exist to remove affected alleles from the population as well as to maintain them. In this situation, equilibrium is affected by a heterozygous advantage favoring viability over homozygotes.
What is an example of positive selection of heterozygotes?
Heterozygosity for sickle cell allele offers protection from malaria and beta-thalassemia
What are AIMs?
Ancestry Informative Markers - alleles that show large differences among populations of different geographic origins
