Modes Of Inheritance Flashcards
What is dominant autosomal?
A characteristic is dominant if it manifests in a heterozygote (ie 2 different alleles at a locus)
- dominance refers to the phenotype
What gene is responsible for brown eyes and how?
The gene responsible OCA-2 controls amount of melanin in melanocytes. Active OCA-2 means brown, inactive OCA-2 means blue.
What is an autosomal dominant condition?
A condition where only one faulty allele/ gene is needed for the condition to be expressed
Can the autosomal dominant disorder arise de novo?
Yes it may, possible mosaicism
Where do autosomal dominant conditions manifest in?
They mainfest in heterozygotes
What are the effects of autosomal dominant conditions?
- Gain of function
- Insufficient amounts of protein being produced (rare)
- Dominant negative effect
What is an example of an autosomal dominant condition?
Huntingtons
What type of pedigree pattern do autosomal dominant conditions show?
Vertical pedigree pattern
What causes Huntingtons disease?
mutation, expansion of a CAG (glutamine) repeat huntingtin
which results in abnormal intracellular huntington protein aggregates
It gains a pathological function and is toxic to neurons resulting in cell death
What are the symptoms of huntington’s disease?
Symptoms usually start 30-50 y/o
Difficulty concentrating, depression, stumbling, involuntary jerking, problems swallowing
What is meant by gain of function?
gene now makes a protein with a new function e.g., constitutively active, aggregates
What is meant by a dominant negative effect?
The mutated form interferes with the activity of proteins it binds e.g., dimers or multimers which reduces activity
How do autosomal dominant conditions effect men and women?
They affect men and women equally and they are equally likely to pass on the condition
Is osteogenesis imperfecta a recessive autosomal disease?
No, it is dominant autosomal
What is osteogenesis imperfecta?
Brittle bone disease
Group of genetic disorders mainly affecting bones
Bones break easily
Mild to severe
What are the symptoms of osteogenesis imperfecta? (4)
hearing loss, breathing problems, short height, blue tinge to white of eyes
What is Type I osteogenesis imperfecta?
insufficient quantities of collagen
What are type II, III, and IV osteogenesis imperfecta?
mutation of collagen results in an abnormal protein has an altered structure and interferes with the function of the normal protein (expressed from the normal gene)
What is the overall result of osteogenesis imperfecta?
Weakening connective tissue particularly bone
What are autosomal recessive conditions?
where carriers of recessive disease have lost a single copy of a gene but the normal one is sufficient to maintain normal function
What does recessive mean?
2 copies of the abnormal gene must be present in order for the disease or trait to develop
What are the usual effects of autosomal recessive conditions?
Loss of function - having both copies results in a completely malfunctioning protein e.g., deletions
Are children usually affected with recessive disorders?
No, normally unaffected, each subsequent sibling of an affected child has a 1 in 4 chance of being affected
What type of pedigree pattern do autosomal recessive conditions show?
Horizontal pedigree
What can increase the risk of autosomal recessive conditions?
Consangious marriages
Why can autosomal recessive conditions skip generations?
Due to the high chance of being a carrier
How are men and women affected with autosomal recessive conditions?
They are affected equally
What type of chromosomes are autosomal recessive genes located on?
Non-sex chromosomes
What percentage of DNA is shared between first cousins?
12.5%
Is cystic fibrosis a recessive disorder?
Yes
What are symptoms of cystic fibrosis? (4.5)
Failure to thrive
The defective chloride ion channel results in impaired Airway defense
Prone to respiratory infections
Digestive issues e.g., meconium ileus
Largest cohort of chronically infected patients
What causes cystic fibrosis?
Mutation, various mutations in gene encoding chloride ion channel (CFTR gene on chromosome 7)
What does the mutation in cystic fibrosis result in?
Defective chloride ion channel
Loss of function, degraded faster or present in inadequate amounts
Who do X-linked recessive conditions mainly affect?
Men (as it is effectively dominant)
How can females have an X linked recessive condition?
They have to be homozygous for the condition
What is the chance of a daughter of an affected male being a carrier of an X Linked recessive condition?
100%
What is an X linked recessive condition?
Where the alleles are located on the sex chromosomes, and since males have XY, a portion of their second chromosome is missing, meaning males have an increased risk of the condition as they only need the one recessive allele to have the condition
What are the probabilities of X linked recessive disorders?
Brothers of affected son have 1 in 2 risk of having disorders
Sisters 1 in 2 chance of being a carrier
What happens to the daughters and sons of an affected father and unaffected mother of an X linked dominant condition?
Daughters - They are all affected
Sons - none affected
What is an X-linked dominant disorder?
Similar to autosomal dominant pattern (seen in both sexes)
Condition is often milder and more variable in females than in males
some diseases only present in female as males not viable
what is the possible mechanism of a dominant x-linked disorder?
gene mutation
causes overproduction of protein
inhibit a function
what is an example of an x-linked recessive disorder?
Haemophilia- more frequent or severe bleeds, different levels of severity, factors VIII or IX
Can female carriers exhibit subtle signs of an x-linked recessive disorder?
yes
Who do Y linked disorders affect?
Only men as females do not have Y chromosome
What type of pedigree pattern do Y linked disorders show?
Vertical pattern with only males affected
What can a y-linked disorder cause?
Mutation in gene cells to produce a defective protein
What are mitchondria?
Specialized organelle of eukaryotes
Share an evolutionary past with bacteria
Have their own DNA
Majority mitochondrial proteins encoded by nuclear genes
- Mutations in these genes cause most mitochondrial disease
Some disease caused by mutations mitochondrial DNA
Who are all your mitochondria inherited from?
Mother
What type of pedigree pattern does mitochondrial inherited disorders show?
Vertical
A mother has a mitochondrial condition. What happens to her children?
They are all affected
Why do mitochondrial disease vary in general?
Mitochondria have multiple copies genome some normal, some mutant (heteroplasmy)
Only express the disease effects if above a threshold
Due to mitochondria endosymbiosis (bacterial origin) they replicate by binary fission
Can lose or gain mutated genes in the process
What causes most mitochondrial diseases?
not all mitochondrial diseases are caused by mutations in mitochondrial DNA
Most are caused by mutations in cell genome and have medalian or sex chromosome linked inheritance
Why do the expression of mitochondrial conditions vary massively in a family?
When the mitochondria replicate, genes can be lost or gained meaning there is an enormous amount of variation
How does severity vary with mitochondrial diseases?
Random segregation
Number of affected mitochondria
Symptoms develop once threshold is reached
Cells different number of mutant mitochondria can change with time
Develops with age due to accumulation of mutant mitochondria
What are normally affected with mitchondrial diseases?
Motor and nerve function
Can present as unrelated multi-system symptoms
Are mitochondrial conditions variable within a family?
Yes
What type of inheritance is it when children of unaffected parents are affected?
X Linked recessive
