Inheritance of human disease Flashcards
what is penetrance ?
the likelihood of having a disease if you have a gene mutation
what level of penetrance is mendelian disorder ?
high penetrance
what mendelian inhertance are there ?
autosomal dominant
autosomal recessive
X-linked
mitochondrial
what is expression ?
variation in disease severity if you have the mutation
what does PCR allow you to do ?
select one small piece of human genome from a patient and amplify it
pieces can be sequenced to find mutations
what are the different types of mutations ?
Promotor and splice site sequence changes
Base changing causing amino acid change
Base change causing premature stop codon
Insertion or deletion of bases
what can happen when a promoter and splice site sequence changes ?
stop transcription
cause abnormal splicing
what can happen when base changing causes amino acid change ?
change in protein sequence
may or may not reduce protein function
main points for autosomal dominant
- Disease seen in all generations
- 50% risk of affected child if parent affected
- Disease severity variable
- Males and females equally likely to be affected
main points for autosomal recessive
- 2 faulty copies of the gene required to cause
disease - Often only one generation affected
- 1 in 4 risk of an affected child if parents are carriers
- Increased likelihood in consanguineous
(incestuous) families - Usually causes loss of function
main points for X-linked
- Y chromosome almost irrelevant
- Haemophilia
- If mother carrier, 50% chance daughter carrier,
50% chance male affected - No male-male transmission
main points for mitochondrial
- Mitochondrial DNA contains important genes for
mitochondrial metabolic pathways and ribosomal
RNAs - Inherited almost exclusively maternally
- Point mutations and deletions occur
- has symptoms
what are the symptoms of mitochonrdrial
Myopathy
Diabetes
Deafness
Optic atrophy
Stroke like episodes
Encephalitis
what are common genetic diseases ?
polymorphism
mendelian disorders
multifactorial disease
Polymorphism
- Promotor – less protein
- Exon – change in protein function or no effect
Mendelian disorders
- High penetrance
- Small environmental contribution
Multifactorial disease
- Genetic change just another risk factor
- Penetrance for any one mutation is low
- Individual genetic factors can be treated the same
way as other environmental risk factors
what are non-mendelian inheritance ?
imprinting
Angelman syndrome
heteroplasmy
what does DNA methylation lead to ?
modification of histones which represses transcription
imprinting
- Differences in gene expression depending on whether a gene is maternally or paternally inherited
- Specific chromosomal regions contain imprinted genes
- Such regions usually contain both maternally and paternally imprinted genes
angelman disease
- Neuro-genetic disorder
o Developmental delay
o Intellectual disability
o Ataxia
o Epilepsy
o Happy demeanour
o Frequent laughing and smiling - Chromosome 15
heteroplasmy
- Different daughter cells contain different proportions of mutant mitochondria
- Severity and nature of phenotype depends on proportion and level of mitochondria and the type of mutation
