Genetics Flashcards
Histones
Proteins that DNA wrap around
Chromatin
Repeating units of nucleosomes
Characteristics of euchromatin
Relaxed, loosely packed, genes are highly expressed
Characteristics of heterochromatin
Tightly packed together, genes are poorly expressed
Harder for enzymes to move past the tightly packed genes
During cell division, chromatin tightly condenses into _____
Chromosomes
What is a centromere?
The constriction point of a chromosomes that divides it into two sections
The location of the centromere gives the chromosome its characteristic shape and can be used to help describe the location of specific genes
Short arm –> p arm
Long arm –> q arm
What is a promoter? - Basic Structure of a Gene
Base-pair sequence that specifies where transcription begins
What is RNA coding sequence? - Basic Structure of a Gene
Base-pair sequence that includes coding information for the polypeptide chain (protein - although not yet in final form) specified by the gene
What is terminator? - Basic Structure of a Gene
Sequence that specifies the end of the mRNA transcript
What direction does nucleic acid synthesis occur in?
Synthesized in a 5’ to 3’ direction
DNA and RNA polymerases can only add nucleotides to the 3’ carbon on the previously incorporated base
What enzyme is responsible for the process of DNA replication?
DNA polymerase
Do all replication errors become mutations?
NO
Only when they are not corrected
What is the “end problem” in DNA replication?
The newly synthesized lagging strand has a gap of about 100 bases
This gap can start to eat into the chromosome, causing it to get shorter and shorter –> eventually lose functionality
What are telomeres? What do they do?
Complex of noncoding DNA & binding proteins at ends of linear chromosomes
Act like a cap on chromosomes
Maintain its structural integrity –> “solve” the end problem
What does a telomerase enzyme do? What kind of cells is it present in?
It maintains telomeric length by adding more tandem repeats to chromosomes
Present only germ cells, stem cells, and cancer cells
What is transcription?
Process of making an RNA copy of a gene sequence
In preparation for synthesizing the protein that gene codes for
3 Steps of Transcription
Initiation
Elongation
Termination
What does RNA polymerase do?
Initiates synthesis
lacks proofreading capabilities
What is an exon?
expressed sequence, translated protein
What is an intron?
intervening sequence removed during splicing, not found in mature mRNA
What is translation
Process by which mRNA is used to direct synthesis of a specific protein
tRNA Structure and Function
Carries amino acid to ribosome to lengthen the growing peptide chain
Recognition between mRNA codon and tRNA anticodon with complementary base pairing
What is the ribosomes job in translation?
Find starting place on mRNA
Line up tRNA on mRNA
Set correct reading frame for codon triplets
Catalyze peptide bonds that hold together amino acids
Releases newly synthesized protein chain when a stop codon is reached
What are Post-Translational Modifications? Why are they important?
Modifications of the polypeptide product of translation, after the translation process, is complete
NOT encoded in DNA, but are essential for the proper functioning of the protein
Increase protein functionality and diversity, regulate activity, localization, and interaction of proteins with other cellular molecules
Central Dogma
DNA
transcription
RNA
translation
Polypeptide
Folding or Post-Translational Modification
FINAL PROTEIN
What is a wild-type allele?
The allele that encodes the phenotype most common in a particular population
The “normal” allele
What is a mutant allele?
Any form of an allele other than the wild type
What is penetrance?
A measure of proportion of individuals in a population who carry a disease-causing allele AND express the disease population
What is complete penentrance?
ALL people with the allele display the disease phenotype
What is incomplete penetrance?
SOME people with the allele do not display the disease phenotype
What is expressivity?
The degree to which a genotype is expressed phenotypically in individuals
Not every mouse expresses purple tail pigment in their phenotype, despite having the requisite allele in their genotype.
What is this an example of?
Incomplete penetrance
Every mouse expresses purple tail pigment in their phenotype, but some tails are dark purple and some are light; pigment intensity varies
What is this an example of?
Variable expressivity
Some mice have dark purple tails, some have light purple tails, and some have tails with no purple pigment
What is this an example of?
Both incomplete penetrance and variable expressivity
Familial Adenomatous Polyposis (FAP) – if you inherit the disease-causing allele, you will get colon cancer, usually at an early age
What is this an example of?
Complete penetrance
Hereditary Non-Polyposis Colorectal Cancer (HNPCC) – if you inherit the disease-causing allele, there is an 80% chance that you will get colon cancer, and can cause cancer in other organ systems
What is this an example of?
Incomplete penetrance with variable expresivity
In people who have the allele coding for the mutation that causes achondroplasia, 100% of them will display the phenotype. This is known as _____
Complete penetrance
In people who have the allele coding for a mutation that causes osteogenesis imperfect, some will have mild disease and some will have severe disease. These differences in disease severity are also known as __________
Variable expressivity
What are the two common types of mutation at the single gene level?
Frameshift mutation
Point mutation
What is a frameshift mutation?
The addition or removal of one or more bases changes the “reading frame”
Alters the primary structure of a protein
Deletion, insertion
What is a point mutation?
Single base (and thus, base pair) substation
May cause affected codon to signify an abnormal amino acid
What are the three subtypes of point mutations?
Missense –> wrong amino acid is made (ex. sickle cell anemia)
Nonsense –> a premature codon is inserted
Silent Mutation –> same amino acid is made (bc redundancy)
Germ cell vs Somatic cell Mutations
Germline Mutation:
- Originates in germ cells
- Entire organism carries the mutation
- Half of the gametes carry the mutation
Somatic Mutation:
- Originates in body cells
- Affects a patch of area
- None of the gametes carry the mutation
What is a monogenic disease?
One gene is mutated and is responsible for the disease
example: Sickle-cell Anemia (HBBgene)
Classification –> location: autosomal or sex chromosomes
What are polygenic and multifactorial diseases?
More than one gene is mutated
Environmental factors may also play a role
example: T2DM
Autosomal Dominant Diseases
Due to a mutation of a specific autosomal gene
1 mutant allele sufficient for disease phenotype to be expressed
Autosomal Recessive Diseases
2 mutant alleles needed for the disease phenotype to be expressed
Unaffected may transmit to offspring
Sex-Linked (X-linked) Disease
Mutation of sex chromosome (X)
Almost all are recessive
Males ALWAYS express // females when XX
If G6PD were deficient in RBC, why would that be especially problematic? What is it about RBCs, in particular?
RBC have no nucleus
When undergoing large amounts of hemolysis, they cannot synthesize more
What are Single-Nucleotide Polymorphisms (SNPs)?
DNA sequence variations where a single nucleotide is altered
What are Genome-wide Association Studies (GWAS)?
seek to identify distribution of SNPs, across diff population, and associations of SNPs, rearrangements and copy number variants with various diseases
Can be used to predict an individual’s risk of developing a disorder
When is/can a gene be expressed?
A gene is expressed when the protein for which it codes is created/synthesized
What is gene regulation?
The process of turning genes on and off
What is the role of miRNAs in gene expression?
Regulate proteins produced, prevent protein from being made
What is epigenetics?
Modifications in gene expression without alteration of genetic structure
does NOT involve mutation, NO change in DNA sequence
What is DNA methylation?
Most common modification in epigenetics
addition of methyl groups
low DNA methylation –> high level of expression
high DNA methylation –> low level of expression
Polymerase Chain Reaction (PCR)
Takes short fragments (10,000 - 40,000 base pairs) and amplifies them to be studied
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)
Used for gene knockout, repression, or editing of a stretch of DNA within a gene
DNA replication is:
Both continuous and discontinuous
You would expect to find telomerase enzyme in which of the following cell types?
Liver cancer cells
Stem Cells
Sperm
Which type of point mutation would result in a protein that is too short?
Nonsense
Sickle Cell Disease is an autosomal _____________ disease and requires _________ copies of the mutated allele for the phenotype to be expressed
Sickle Cell Disease is an autosomal RECESSIVE disease and requires TWO copies of the mutated allele for the phenotype to be expressed
In people who have the allele coding for a mutation that causes Marfan Syndrome, an autosomal dominant disease, some people have mild symptoms, such as being tall and thin with long, slender fingers. Others also have life-threatening dysfunction involving the cardiovascular system. These differences in disease severity are also known as ___________
Variable expressivity
T/F
Offspring with XY chromosomes always express the disease if they inherit the mutated gene on the X chromosome
X-linked/Sex-linked Diseases
True
T/F
All the offspring with XX chromosomes born to a father who has the disease will also have the disease.
X-linked/Sex-linked Diseases
False
We do not know the genetic status of the mother
T/F
Offspring with XX chromosomes always express the disease if they inherit 1 copy of the mutated gene on the X chromosome.
X-linked/Sex-linked Diseases
False
Offspring with XX chromosomes would have to inherit 2 copies of the X chromosome with the mutated allele in order to express the disease. If they inherit 1 X chromosome with the mutation, their other X chromosome (without the mutation) can function normally
T/F
Offspring with XY chromosomes, born to an affected father and a mother with no mutated gene on an X chromosome, will never inherit the disease.
X-linked/Sex-linked Diseases
True
What is the clinical significance of familial hypercholesterolemia?
Atherosclerotic plaques would be expected to form in an affected person’s coronary arteries
An affected person will have very high blood levels of LDL cholesterol
Adolescents who are affected may have coronary artery calcification
What is true of micro RNAs (miRNA)?
They provide a feedback system when a gene is expressed.
CRISPR is a technique that can be used to:
Edit a gene
Silence a gene
Missense Mutation Result
Wrong amino acid is made
ex. sickle cell anemia
Nonsense Mutation Result
Premature stop codon inserted
Shorter protein
Silent Mutation Result
Same amino acid is made
Bc redundancy
Autosomal Dominant Example: Familial
Hypercholesterolemia (FH) –> autosomal dominant or recessive?
Autosomal dominant
Patho of Familial Hypercholesterolemia (FH)
The gene that is mutated in Familial Hypercholesterolemia codes for a receptor in the liver that removes LDL cholesterol from the blood
Now cannot remove LDL-C from the bloodstream
Reduced clearance of LDL-C from circulation –> high levels of plasma LDL-C from birth
Increased atherosclerotic plaque formation w/ subsequent calcification
Sickle Cell Disease is autosomal ____
recessive
SCD Patho
the specific mutation found in sickle cell disease is a missense
causes a single amino acid substitution
causes the sickling shape
Results in ischemia, jaundice, anemia, destruction of the spleen, increased infections,
G6PD Deficiency is a _____ disease
X-linked recessive disease
G6PD Deficiency S/Sx
Jaundice, fatigue, tachycardia 2/2 acute hemolytic anemia
Which disease appears to be protective against progression to severe malaria in about 2/3 of males?
G6PD Deficiency
