Genetics week 6 + clinical info Flashcards
What is another way to write mitochondrial DNA
- mtDNA
Where is mitochondrial DNA inheritied from
- Maternal line
What does the mitochondrial encode and why
- 13 polypeptides
- 2 rRNAS
-22 tRNAs
For oxidative phosphorylation
What are key features of mtDNA(mitochondrial DNA)
- lacks introns
- Has mutation rate 10x higher than nucler DNA
-Susceptible to damage
Why is the mitochondrial DNA susceptible to damage?
- Due to fewer repair mechanisms
- Exposure to free radicals during oxidative phosphorylation
What is heteroplasmy? (in relation to mitochondrial DNA)
- Where cells may contain a mix of normal and mutant mTDNA molecules
- The amount/porportion of mutant mtDNA detrmines the severity of mitochondrial diseases
What type of organs are more severly affected by mtDNA molecules
- Organs with high ATP demands
Name the types of mitochindrial mutations
- Misense mutations
- Single base mutations in tRNA genes
-Duplication and deletions
What does misense mutations lead to
LHON
What does LHON lead to
- Rapid loss of vision in the central field
What does single base mutations lead to
- MERRF
- MELAS
What does duplications and deletions lead to
-Kearns-sayre disease
- Pearson syndrome
- CPEO
What does kearns-sayre disease lead to
- Muscle weakness and heart failure
What is genetic imprinting?
- It is a form of gene silencing, where only 1 allele of a gene is transcriptionally active, depending on the parent of origin
Describe the mechanism for geneomic imprinting
-The transcriptionally inactive alleles is refered to as imprinted.
-The imprinted genes are transcriptionally silent due to epigenetic modifications such as:
- DNA methylation
- Histone hypoacetylation
- Chromatin condensation(preventing transcription factor binding)
What does chromatin condensation do
- Prevent trasncription fators from binding
What is prader willi and angelman syndrome caused by
-Deletion of several megabases(Mb) on the long arm of chromosome 15
How is prader willi syndrome inherited
-Deletion inhertied from the father
How is Angelman syndrome inherited
- Deletion inherited from the mother
What are features of someone with Prader willi syndrome
- Obesity,
- small hands and feet
- Short stature
- poor muscle tissue(hyptonia)
What are the features of someone with Angelman syndrome
- Seizures
- Intelectual disability
What is Mosaicism
- Refers to the presence of 2 or more genetically distinct cell lines within an individual.This can occur do to several mechanism
What are the mechanisms that can cause mosaicism
- Chromosomal nondisjunctions during mitosis
- Gene mutations during development
- Chromosome inactivation in females
What happens in chromosomal nondisjunction during mitosis
- When a chromosome does not separate properly during cell division therefore the daughter cell will have an abnormal number of chromosomes
What are the types of mosaicism?
- Germaline
- Somatic
- Confined placental mosaicism
When does germlin mosaicism occur
- Occurs when a mutation is present in the germ cells(sperm and egg) but not the somatic cells
When does somatic mosaicims occur
= Occurs when there is mutations in some of the body cells but not the germline cells
When does confined placental mosaicism occur
When chromosomal abnormalities are present in the placenta
What are triplet repeats
Sequences of 3 nucleotides that are repeated in tandem within a gene
Explain the concept of normal variation in triplet repeats
- A certain number of triplet repeats is considered normal , but expansions beyond this range can lead to disease
Explain the concept of disease mechanisms in triplet repeats
- The expansion of triplet repeats can disrupt gene function in several ways depending on the location of the repeats within the gene
What is osteogensis imperfecta caused by
- Defects in Type 1 collagen
which leads to weakened bone strength
Whats the most common substitution leading to OI
Sub of glycine in the collagen triple helix
What are they symptoms of OI
- Short stature
- Blue sclerae
- Hearing loss
- Bone deformitites
- Dental issues
What is the most severe type of OI
What is the midelst type of OI
- Type 2
- Type 1
How many different types of OI are there
1,2,3,4,5,6,7,
What is cystic Fibrosis(CF) caused by
- Mutations in the CFTR gene, which encodes chlorine ion channels involved in fluid transport
Whats the most common mutation in CF
and its effect
-F508
- Deletion of 3 nucleotides
resulting in the loss of the amino acid phenylalanine
What type of disorder is cystic fibrosis
- Autosmal recessive disorder
What is retinoblastoma
- Malignant tumor of the retina
What is retinblastoma caused by?
- Mutations in the RB1 gene which is a tumor suppressor gene located on chromosome 13
What is the function of the TSG
regulates cell growth
What type of inheritance pattern is Huntingtons disease
- Autosomal dominant
What is the role of the HTT gene in Huntington’s disease
It encodes for the Huntington protein
What is Huntington’s disease?
- Neurodegenerative disorder characterised by motor, cognitive and psychiatric
What is huntingtions disease caused by
- Expansions of a CAG trinucleotide repeat in the HTT gene that codes for Huntington protein
What does neurofibromatosis effect
- Effects the development and growth of nerve cells
What is neurofibromatosis caused by?
- Caused by mutations in the NF1 gene which encodes a protein called neurofibromin that acts as a tumor suppressor gene
What is Marfan syndrome
- A connective tissue disorder, that affects multiple organ systems
What is the most common form of marfan syndrome
- Marfan syndrome type 1
What is marfan syndrome caused by
- Mutations in the FBN1 gene which encodes the protein fibrillin-1 . This weakens the connective tissues
What are symptoms of marfan syndrome
- Tall stature
- Long limbs
- Scoliosis
- Cardiovascular abnormalities
What are the symptoms of duchenne muscular dystrophy
- leads to muscle weakness and degradation
What is duchenne muscular dystrophy caused by
- Mutation in the DMD gene which encodes dystrophin, which is a protein that is essential for the structure of the muscle fibers
What is Hemophilia A
- A bleeding disorder in the f8 gene which encodes clotting factor V111
What are the symptoms of the Hemophilia A
- Severe bleeding
- Blood clots
- Easy bruising
What type of inheritance is retinoblastoma
Autosomal recessive inheritance
What type of inheritance is Marfan syndrome
Autosomal dominant
