Genetics week 3,4,5 Flashcards
Where does genetic variations arise from?
From mutations, which are changes to the DNA sequence
Where do mutations occur in?
Germaline cells( that produce gametes) which can affect gametes
Somatic cells( Can lead to cancer)
What is an allele
Variations of a gene that difers in DNA sequence
What is the locus
specific location of a gene on a chromosome
What are mutations
changes in the DNA sequence
NAME the type of single-gene mutations
- Base pair substitutions
- Silent substitutions
NAME the 2 types of base pair substiutions that alter amino acids
Missense Mutations
Nonsense Mutations
Describe the 2 single gene mutations
- Base pair mutations:When a base pair is replaced with another
Silent mutations: No change in amino acid sequence due to genetic code redundancy
Describe the 2 basic types of muations
-Missense mutations: Alters one amino acid, potentially affecting protein function
-Nonsense Mutations: Creates a stop codon, leading to early termination of translation or mRNA decay
What is insertions and deletions
adding or removing base pairs
What is the frameshift mutation
It alters reading frame if the number of bases is not a multiple of 3 changing downstream amino acids
What is gene duplication
It is duplicating entire genes
What is Mobile Element insertions and name the diseases it has been linked to
Certain DNA sequences can copy themselves into new locations, causing frameshift mutations.
This has been linked to diseases like neurofibromatosis and muscular dystrophy
What is Tandem Repeat Extensions
Repeated DNA sequences may expand causing genetic diseases. Theses expand repeats can be passed to offspring, contributing to conditions like huntingtons disease.
Name the 3 consequences of mutations
- Gain of function mutations
2.Loss of function mutations - Dominant negative mutations
Explain the gain of funtion mutation and the consequences
- Leads to an increased or innapropriate protein activity, resulting in a novel protein product( which can lead to huntingtons disease) and it results in overecpression (which can lead to Charcot-Marie-Tooth disease)
Explain the loss of funtcion mutation and the consequences
- Results in a reduced or eliminated protein activity, often associated with recessive disorders where 50% of protein functions remain sufficent.
And it can lead to hapiloinsufficency, which occurs when 50% functions is insufficent causing domina disorders like familial hypercholesterolemia
Explain the Dominant Negative mutations and the consequences
Results in an abnormal protein that interferes with the normal protein in heterozygotes. This is common in multimeric proteins such as Type 1 Collagen( which leads to distorted protein structure)
What does gain of function mutatins result in
- Novel protein prodcut which can lead to huntingtins disease
- Overexpression which can leas to Charcot- Marie-Tooth disease
What does loss of muation result in?
- Hapilosuffiency, which occurs when 50% function is insufficent causing dominant disorders like familial hyppercholesterolemia
Name the three types of hemoglobin disorders
- Structural abnormalities
- Thalassemias
- Hereditary Persistence of fetal hemoglboin(HPFH)
Explain structural abnormalities as a hemoglobin disorder
- Mutations that alter the hemoglobin molecule
Explain Thalassemias as a hemoglobin disorder
- It reduces the quantity of structurally normal a and b globin chains keading to imbalanced hemoglobin synthesis
Explain HPFH as a type of hemoglobin disorder
- It causes the continued production of fetal hemoglobin after birth which can compensate for reduced adult hemoglobin without causing diseases.
Describe the structure of hemoglobin
- Tetramer with 2 alpha and beta polypeptide chains
- The beta chains are encoded on chromosome 11 and the alpha chains are encoded on chromosome 16
- Equal production of alpha and beta chains is tightly regulated for normal oxygen transportation by hemoglobin
What is sickle cell caused by?
- It is caused by a single missense mutation, that substitutes valine for glutamic acid at position 6 of the glboin chain, leading to abnormal hemoglboin strutcure.
Explain the mechanism of sickle cell disease
- Under low oxygen, hemoglobin aggregates, causing erythrocytes to take on a sickle cell shape
- Sickled cells are rigid amd they get stuck in capillaries and adhere to vascular walls
What are the two types of Thalassemia
A- thalassemia
b - thalassemia
Explain what results in Thalassemia
- It results from mutations that reduce the amount of a and b globin chains , leading to excess chains of the other type
Explain alpha Thalassemia and what it is caused by
- caused by deletions of a globin genes
- Loss of 1 or 2 genes have minimal effect but the loss of 3 genes cause HbH disease with anemia
- Loss of 4 a genes leads to hydrops fetalis , which is fatal before or shortly after birth
Explain beta Thalassemia and what it is caused by
It results from single base mutations rather than gene deletions
- individuals w 1 mutated beta globin genes have beta thalassemia minor( mild or no symptoms)
- indivdulas w 2 mutated beta globin genes may develop b thalassemia major
What are symptoms of thalassemia
- anemia
- growth reduction
- increased infection risk
bone deformities
What is genotype?
- An individuals genetic makeup at a specific locus
What is phenotype
Observable or clinical traits
Explain the envirnomental influences on genotype-phenotype
They can affect how the phenotype is expressed
What is the basic pedigree structure used for?
- Show family relationship and who is affected or not affected by a genetic disease
Explain the degrees of relationships
1st- Parents, offspring,siblings
2nd- Grandparents, grandchildren,uncles,aunties, nieces and nephews#
3rd- cousins, great grand children
What are the characteristics and transmission pattern of Autosomal Dominant Inheritance?
- The affected offspring usually results from 1 hetergozygous parent and one unaffected parent
Transmission pattern: - Both males and females are likely to inherit
- There is no generation skipping
- Father to son transmission is possinle
What is the reccurence risk?
This is the probability that parents with a genetic disease will produce affected offspring
What is the autosomal dominant recurrence risk?
When one parent is affected and the other is unaffected so each child has a 50% recurrence risk
What is the inheritance pattern for autosmoal recessive diseases + the % of affected, unaffected and carriers
-From 2 heterozygous carriers
- Punnet square shows how 25% of offpring will be affected, 25% unaffected and 50% will be carriers
What is the Transmission characteristics(1) of autosmal recessive inheritance?+ where is this disease seen more in
- Both males and females have equal chance of inheritance
- The diseases is typically seen in syblings than cross multiple generations
What is quasidominant inheritance+ the reccurence risk?
- When a carrier of a reccesive allele mates with an affected homozygote
The reccurence risk is 50%
What is De Novo mutation?
A mutation that can cause a genetic disease in a child with no family history
What is Germaline Mosaicism
When a mutation affects a parents germaline cells but not somatic cells, allowing them to pass the mutations to multiple offsprings without being affected themselves
What is Age-dependent penetrance + example
When there is a delay in the onset of a gentic disease causing the symptoms to appear late in life rather than at birth.
e.g Huntingtons
What is Variable expression + example
refers to the differing severity of the genetic diseases phenotype
-neurofribromatosis
What is pleitropy
When a single gene has multiple effects on different body systems
What is Anticipation?
Genetic diseases that have an earlier onsent in more recent generations
What is imprinting?
Certain genes are expressed only if inherited from a specific parent
Why are female stomatic cells inactivated?
- To balance the levels of X-linked gene products between male and femals
What happens once a x chromosome is inactivated?
- It will remain inactive and It leads to a permenant mosaic pattern of X chromosome activty in females
X inactivation
Why does the Lyon hypothesis state?
- It states that X inactivation occurs early in female embryonic development
- And the X chromosomes contributed by the father is inactivatedd in some cells
and the cells that the X chromsome contributed by the mother is inactivated.
Where is the XIST gene and role
-It is in the X inactivation center, which is crucial for X chromosomes inactivation.
- XIST,produces a long noncoding RNA (lncRNA) that is transcribed only on the inactive X chromosomes in females.
Where is the IncRNA(long noncoding RNA) and its function
-Remains in the nucleus
-coating the inactive X chromosomes and recruiting proetins to inhibit transcription
Where are sex linked genes located and where is the main focus?
-On the x or y chromosomes
- Main focus is on the x linked genes as y chromosomes contain few genes
what is X-linked inheritance categorised as
- X-linked Recessive or dominant
Why is the classfication of X-linked inheritance ambigous?
-Due to variable expression of traits
- incomplete penetrance
- Effects of random x inactivation in females
What is incomplete penetrance?
When not all carriers show symptoms
Name the diseases caused by X-Linked reccesive genes
- Hemophilia A
- Duchenne Muscular dystophy
- Red - green colour blindness
What is the inheritance pattern of X-linked recessive inheritance
- The females inherit 2 X chromosomes so they can be:
- Homozygous normal,heterozygous (carrier) or homozygous for the diesease allele
- The males inherit one x chromosomes and they are hemizygous, so they will express an x linked disease if they inherit a disease causing allele
What are the inheritance characteristics of X linked recessive diseeases?
- Generation skipping (when a female carrier passes the genese without expressing it)
- No father to son transmisson ( as the father passes the Y chromosome)
- Affected males pass the gene to all daughters(who are carriers)
By using the common mating pattern in X linked resseive disorders give the percentages of the offspring being carriers and etc
50% daughters are carriers
50% sons are affected
50% of daughters and sons are normal
Name 3 examples of X linked dominant diseases
- Rett syndroome
-Incontinentia Pigmentic Type - Hypophosphatemic rickets
Explain the difference in the effect of the Xlinked dominant disorders in males vs females
-Males are hemizygous and they experience severe effects
- Females have milder symptoms due to then have one noermal x chromosome
What is the inheritance pattern in Xlinked dominant inheritance.
Affected females: There is a 50% chance of passing the allele to offpsings
Affected males:the affected allele is passed to all daughters
What are the inheritance characteristics of Xlinked Dominant inheritance
- Both male and females can be affcted, but females are more likely
-No father to son transmission - Affected fathers pass the trait to All daughter
Generation skipping is rare/uncommon
What are barr bodies
Dense chromatin masses in the femal nuclei
What do Barr bodies show?
- Reduced Transcriptional activity
- Delayed DNA replication during the Sphase
Explain the biochemical evidence supporting the lyon hypothesis
-They enzyeme G6PD being coded on the X chromosome in equal amounts in amels and females due to doasge compensation
