Biochemistry I Flashcards
Medical genetics
refers to the applications of genetics to medical practice: studies of inheritance of diseases in families, analysis of molecular mechanisms of disease, molecular techniques for DNA based diagnosis, gene therapy, genetic counseling
Many diseases in children and adults have a?
Genetic component
Genotype
Represents the genetic constitution of an organism. It is the summation of the entire DNA within the cell or organism.
What influences genotypes?
Mutations
In the absence of mutations, the genotype is?
Constant
Mutations can be generated by:
- DNA fails to copy accurately
- Internal/external influences can create mutations
Mutations are…
random
Phenotype is also called
trait
Phenotype represents the
observable character of a cell or organism
What influences phenotype?
genotype and environment
Mutations do not always?
Alter a organism’s phenotype
Phenotypes are in?
constant change, depending on the environmental conditions: diet, T, light, oxygen, drugs, infection.
The same disease could manifest _________ in two different environments
differently
Do you know an example of a metabolic disease in which an environmental factor triggered the disease phenotype?
G6PD deficiency
If there is a change in the genotype, does it mean a change in phenotype?
Not necessarily, it could be silent or just not affect the phenotype.
If there is a change in the phenotype, does it mean there was a change in the genotype?
Not necessarily, it could be from environmental factors.
Mutation definition
alteration of DNA sequence, in either germline cells (cells that produce gametes) or somatic cells (all other cells)
Mutations are based on the _________ nature of the change in DNA
molecular
Point mutations
1bp substituted
Insertions/Deletions
more than 1bp added or removed
Point mutations represent ______ base pair changes in the sequence of DNA
single
Transitions
(type of point mutation) a purine is replaced by a different purine or a pyrimidine is replaced by a different pyrimidine
Tranversions
(type of point mutation) a purine is replaced by pyrimidine or vice versa
Consequences of point mutations (3)
- missense (change in AA)
- nonsense (stop codon)
- silent (no change in AA)
Point mutations do not always affect the phenotype because they can be?
Silent or some missense mutations
Point mutations that affect the phenotype are often the result of either
missense or nonsense mutations, but are not necessarily restricted to the coding region.
Hemophilia B gene
Factor IX
Hemophilia B type of mutation
point mutation in the gene promoter
Hemophilia B gene is in the _____ chromosome
X
Tay-Sachs gene
HEXA
Tay-Sachs type of mutation
point mutation in the splicing site
Tay-Sachs is a what disorder?
Lysosomal Storage disorder
Sickle-cell anemia gene
HBB (B-globin)
SCA type of mutation
missense point mutation in the coding sequence
(transversion)
SCA has a high frequency in
african americans
Neurofibromatosis type 1 gene
NF1
NF type 1 type of mutation
nonsense point mutation in the coding sequence
NF type 1 is highly _______:
variable: cafe au lait spots and neurofibromas
B-thalassemia gene
HBB (B-globin)
B-thalassemia type of mutation
different types of point mutations
B-thalassemia causes decreased production of?
B-globin
Tay-Sachs (most common variant)
HEXA gene
Small insertion of 4 bp in coding sequence
GM2 buildup in neuronal lysosomes
Cystic Fibrosis (most common variant)
gene
CFTR (chloride channel)
CF (most common) is caused by
a small deletion (3bp) in coding sequence. Causes the loss of a single amino acid from the protein, but does not alter the remainder of the amino acid sequence.
CF has more than ________ mutations reported
1,000
a-thalassemia gene
HBA (a-globin)
a-thalassemia type of mutation
large deletion as a result of aberrant recombination
a-thalassemia causes
decreased production of a-globin
Charcot-Marie-Tooth disease gene
PMP22
Charcot-Marie-Tooth disease type of mutation
large insertion as a result of aberrant recombination
Charcot-Marie-Tooth disease is the most common?
inherited neurological disordre
Deletions and insertions can range from?
a few nucleotides to millions of nucleotides
When a small deletion or insertion occurs within the coding region of a gene and is not a multiple of three, it can result in?
significant change in the amino acid sequence of the gene
insertion/deletion of 1-2 bp (or multiples)
frameshift mutation, you lose the meaning of the message/code
insertion/deletion of 3 bp (or multiples)
in frame mutation
large deletions/insertions are usually the result of
aberrant recombination between highly similar or identical sequences of DNA
aberrant recombination
refers to recombination after misalignment, which can create chromosomes with three copies of genes and chromosomes with only one copy of the gene
Example of large deletion in a-thalassemia
Healthy and silent carrier
Healthy: Function genes are 4, a-chain production is 100%, genotype if aa/aa
Silent carrier: Functional genes are 3, 75% a chain production, genotype is aa/a-
a-thalassemia trait
mild anemia, microcytosis
number of functional genes = 2
a-chain production is 50% and genotype is a-/a- or aa/–
HbH (B4) disease
moderately severe hemolytic anemia
functional genes = 1, a-chain production is 25% and genotype is a-/–. Starts becoming more severe here.
Hydrops fetalis or homozygous a-thalassemia
number of functional genes is 0, a-chain production is 0%, and genotype is –/–, not comptablie with life - miscarriage.
Silent carriers of a-thalassemia are
asymptomatic
A mating between two silent carriers has a _______ chance of a newborn with a-thalassemia (mild anemia)
1/4
A mating between a silent carrier an individual with a-thalassemia trait has a ______ chance of a newborn with HbH disease
1/4
Epigenetic changes are not true
mutations
Epigenetic changes represent
heritable alterations in phenotype without a true alteration in genotype
Example of epigenetic change
altered methylation of cytosine resides in the DNA
Highly methylated DNA is transcriptionallly
silent
Heavy methylation could cause genes that are normally expressed to be?
silent
Epigenetic modifications, triggered by environmental factors, can contribute to alter gene expression in a
heritable manner
Methylation does not equal
Mutation. It allows modulation of gene expression without modifying the actual DNA sequence.
Polymorphism definition
genome variations are differences in the sequence of DNA among individuals (changes in the nucleotide sequence). Changes in the DNA sequence that are frequent (more than 1%)
Mutation and polymorphism represent changes in the DNA sequence but differ in
frequency they are present in the population
A polymorphism is a _________ ______ mutation.
Commonly seen mutation, with a frequency of 1% or higher. Represent the presence of two or more variants of a specific DNA sequence in the population.
Polymorphisms do not affect the?
fitness of the organism
if the polymorphism is deleterious…
natural selection would keep them at very low frequencies
if the polymorphism is advantageous, their frequency would be expected to be…
very high, much higher than 1%
Much of the interindividual variation seen in people is attributed to
polymorphism
SNPs refer to
single nucleotide polymorphisms, where different people have one different nucleotide at given location on a chromosome
We can differentiate __________ or more types of polymorphisms, based on the length of?
Three or more types of polymorphisms, based on the length of the repeats (not the number of repeats)
Each repeat is typically present in at least ___ to more than ____ repeats
in at least two to more than 20 repeats
STRPs are
micro-satellites that are repeats of 2-6 bp
VNTRs are
mini-satellites that are repeats of 20-70 bp
CNVs are repeats of
> 1,000 bp to about 2 million bp
When polymorphisms are present in both parents
those children are their biological children
When one child has a polymorphism of one parent, but not the other the child is probably
a stepchild
Human populations are typically in ___________ ___________ ________ for most loci. However, deviations from equilibrium can be produced by a number of reasons.
Hardy Weinberg Equilibrium.
Natural selection
increases the frequency of favorable mutations, and decreases the frequency of variants that are unfavorable in a given environment.
ex: heterozygote advantage for the sickle cell mutation, cystic fibrosis (CFTR mutation) and resistance to typhoid fever, PKU and resistance to fungal infecitons
Genetic drift
refers to the change in frequency of some genotypes in a population where, BY CHANCE, not natural selection, some individuals leave behind a few more descendants (and genes) than others
Bottleneck effect
a type of genetic drift. a catastrophe kills a large portion of the population. genetic drift happens to all populations, but has a more significant effect on small population
ex: achromoatopisa in 1/10 population in Micronesian atoll of Pingelap
Founder effect
a small group separates from a larger population to establish a new population
ex: BCKD deficiency (maple syrup urine disease) in the Mennonite community of Lancastershire, PA occurs in 1/176 live births, compared to only 1/180,000 in the US population.
Gene flow (migration)
refers to the exchange of genes among populations
ex: sickle cell disease in African Americans vs African populations, ex: B allele int he ABO blood type
Non-random mating
consangunity
Genetic shuffling is?
crossing over during meiosis
New mutations
Ultimately the source of all new genetic variation in populations. In general, mutation rates are comparable from population to population.
2 identical twins
100% identical = 0% difference
2 unrelated humans
99.9% identical –> 0.1% difference = 1 in 1,000 bp
Why do we have so little variation but are still unique
We are a relatively new species. Prior to 80-100,000 years ago there were no modern humans outside of Africa, and we only had about 4,000 generations to introduce cahgnes in our genome.
0.1% difference out of 3+ billion base pairs is over…
3 million bases being commonly variable in humans
