gene mutation Flashcards
true or false:
mutation can affect any part of the genome
true
it refers to the process of altering a DNA sequence
mutate
- substitution of a single dna bases
- deletion or duplication of tens, hundreds, thousands bases/ of entire chromosomes
what are the effects of a mutation
“loss-of-function”
gene’s product is reduced or absent
recessive
“gain-of-function”
gene’s activity changes
dominant and toxic
people who have loss of function mutations but are healthy
knockout mutations
- genetic alterations that completely inactivate of a specific gene
a variant present in more that one percent of a population
polymorphism
variant refers to polymorphism and mutations
example:
A polymorphism is just a common change in DNA that lots of people have. It’s so common that at least 1 in every 100 people has it.
Think of it like hair color - having brown or black or blonde hair are all common variations.
this term refers to the
mutation:
mutant:
mutation:
refers to genotype
change at dna or chromosomes level
mutant:
phenotype and also describes and allele
what does the phenotype in the context of diseases describe?
it describes the observable sign and symptoms
this is a major structural protein in connective tissues, skins, bones and tendons
collagen
- provide strength and elasticity
what happens if there is mutations affecting collagen
lead to various connective tissue disorders
mutations in COL7A1 gene that encodes type VII collagen breaks down fibrosis that attach epidermis to dermis
dystrophic epidermolysis buliosa
osteogenesis imperfecta type I signs and symptoms (phenotype)
easily broken bones
blue eye whites
deafness
it is the inactivation of a1 collagen gene (COL1A1 or COL1A2) reduces number of collagen triple helices by 50%
osteogenesis imperfecta type I
difference between germline and somatic mutations
change occurs during dna replication before
meiosis: germline
mitosis: somatic
occur in
reproductive cells: germline
non-reproductive cells: somatic (other than the sperms/ exons)
passed to offspring
can: germline (heritable)
cannot: somatic
*germline affects all cells of an indiv while somatic is limited to specific cells
a person has 2 or more sets of dna in their body rather than just one so this happens when the mutation occurs in some cells but not others and creates patches of genetically diff cells in the body
somatic mosaicism
[The key things to remember are:
Normally all cells have the same DNA
But sometimes a mutation happens in just some cells
That creates patches of cells with slightly different DNA
It’s like having multiple “sets” of DNA in your body]
it is the subset of genetic disorders that arise from mutations in the same gene but can lead to different clinical manifestations or phenotypes
allelic diseases
- diff clinical phenotype caused by mutations in the same gene
[Imagine there’s a gene that controls how your muscles work. A mutation in that gene could lead to one type of muscle disease, but a slightly different mutation in the same gene could cause a different muscle disease.]
[So in simple terms, allelic diseases are genetic disorders tied to the same gene, but with flexibility in how they actually impact a person’s health and body functions. The gene is the same, but the effects can differ.]
how can the mutation occur
spontaneously
induced by exposure to a chemical or radiation
an agent that causes mutation
mutagen
naturally occurring mutations due to errors in DNA replication or repair mechanisms
Spontaneous Mutations
- DNA polymerase errors during replication
- can manifest gonadal mosaicism [a parent has a mutation in some sperm or oocyte bcs spontaneous mutations occurred in the developing testis or ovary and was transmitted only to the cells descended from the original cell burning the mutation]
New mutations not inherited from parents.
De Novo Mutations
occurs due to a new autosomal dominant
mutation.
A new mutation that occurs in an individual
Caused by external agents (mutagens)
Induced Mutation
they r the chemicals and radiation can induce mutations.
induced- to make it happen intentionally
Substances that chemically alter DNA bases cause structural changes.
Chemical Mutagens
- Examples: Alkylating agents, acridines (adding/removing bases).
High-energy particles that can damage DNA
Radiation
- Examples: X-rays, UV light.
- Radiation can cause base deletions or chromosome breaks.
Organisms or their products that cause mutations.
Biological Agents
Certain viruses that integrate into host DNA.
Naturally occurring environmental mutagens. Physical or chemical factors in the environment that can lead to mutations.
Natural Mutagens Environmental Factors
- Cosmic rays, sunlight, and radioactive substances in the Earth’s crust.
- Pollution, certain dietary factors, and temperature changes.
what is the primary characteristics of gonadal mosaicism
mutations that exist only in some sperm or oocytes of a parent
what is the best known way to test the biological agents
ames test
- assess the mutagenicity of substance using bacteria
Change in a single DNA base.
Point Mutations:
silent mutations
- Transitions: Purine Purine (A G) or
Pyrimidine Pyrimidine (C T). - Transversions: Purine Pyrimidine (A or G T or C).
Change in a DNA base that does not alter the amino acid sequence
silent mutations
No change in protein function due to redundancy in genetic code.
Change in a DNA base that results in a different amino acid.
Missense Mutations
May lead to altered protein function. Example: Sickle cell disease due to hemoglobin mutation
Changes a codon that specifies an amino acid into a stop codon (UAA, UAG, or UGA).
Nonsense Mutations
Results in truncated proteins, e.g., factor XI deficiency.
Caused by insertions or deletions that alter the reading frame.
Frameshift Mutations:
insertion
deletions
Alters the entire amino acid sequence downstream.
Insertions vs Deletions
Insertions:
add of 1 or more dna bases
Deletions
of 1 or more dna bases
- both frameshift altering downstream aa
Mutation type where small parts of the DNA sequence are copied and added, leading to increased repeat number across generations.
Expanding repeats
Example: Myotonic dystrophy; repeat numbers increase severity over generations.
- add stretches of the same amino acid to a protein.
Alteration of sites where introns are normally removed from mRNA.
Splice-Site Mutations
may cause exon skipping or inclusion of introns,
e.g., cystic fibrosis due to intron retention.
DNA sequences similar to functional genes but not translated into proteins. May interfere with gene expression.
pseudogenes
[old, non-functional copies of genes that are still part of our DNA but don’t actually do anything anymore.]
“Jumping genes” that can disrupt gene function by moving to different locations in the genome
transposons
Specific DNA sequences that vary in the number of copies among individuals, can range from a few bases to millions.
Copy Number Variants (CNVs)
[sections of DNA that are repeated a different number of times in different people. These sections can be short or very long, ranging from just a few DNA bases to millions.]
mitochondrial DNA vs nuclear DNA
mitochondrial DNA:
higher mutation rate
have less efficient dna repair mechanism
nuclear DNA:
not dangerous UV wavelengths:
dangerous UV wavelengths:
not dangerous UV wavelengths:
longer - UVA
dangerous UV wavelengths:
shorter - UVB
damage dna by forming an extra covalent bond btwn adjacent (same strand) pyrimidines, particularly thymine
what are the types of dna repair
- photoreactivation
- photolyases
- bind and break bonds in pyrimidine dimers using energy - excision repair
a. nucleotide excision repair
- removes and replace the pyrimidine dimer and a few surrounding bases
b. base excision repair
- only target oxidative damage
- mismatch repair
-enzymes excise the mismatched nucleotide n replace it with the correct one
how does the human dna damage by UV light is corrected
specifically by nucleotide excision repair
this check and correct errors that occur during dna replication
mismatch repair
this causes dwarfism, intellectual disability, and brittle hair and scaly skin, both with low sulfur content
Trichothiodystrophy
people with this type of colon cancer have a breakdown of mismatch repair, which normally keeps a person’s microsatellites all the same length
Inherited Colon Cancer
Hereditary nonpolyposis colon cancer (HNPCC)
autosomal recessive, and results from mutations in any of seven genes
Xeroderma Pigmentosum (XP)
seven gemnes:
XPA
XPB
XPC
XPD
XPE
XPF
XPG
A child with XP must stay indoors in artificial light, because even the briefest exposure to sunlight causes
painful blisters. Failing to cover up and use sunblock can cause skin cancer
This multisymptomatic condition is the result of a defect in a kinase that functions as a cell cycle checkpoint
Ataxia Telangiectasia (AT)
symptoms include:
poor balance and coordination (ataxia)
red marks on the face (telangiectasia)
delayed sexual maturation
high risk of infection
diabetes mellitus
