Lecture 17 Flashcards
mitochondrial inheritance as seen on a pedigree?
- all offspring of affected female are affected
- only females transmit the disease
- can occur in both genders
Explain heteroplasmy?
The severity of the disorder depends on the number of mitochondria that have the mutant gene
explains variable expression
Examples of mitochondrial diseases
- Leber hereditary optic neuropathy
- MELAS
- MERRF
example of a digenic disorder?
Retinitis pigmentosa
Imprinting disorders
Prader Willi syndrome
Angelman syndrome
Triplet repeat disorders
Huntington disease (autosomal dominant) Myotonic dystrophy (autosomal dominant) Fragile X syndrome (X-linked)
How do digenic disorders occur?
Mutations in two genes (A, B) are additive and necessary to produce the disorder
retinitis pigmentosa
digenic disorder
progressive visual impairment
a result of a mutation in two independent genetic loci (ROM1 and peripherin)
Heterozygotes for gene A and gene B have retinitis pigmentosa
Prader- willi syndrome
microdeletion of paternal chromosome 15
microdeletion of the paternal SNRPN gene
no active copy of the SNRPN gene (maternal copy is silenced)..but has two active copies of the UBE3A gene
symptoms of prader-willi syndrome
Children are usually obese, have mental and developmental delay and underdeveloped genitalia
how can methylated DNA be analyzed?
southern blot
PCR and DNA sequencing
angelman syndrome
deletion of the maternal gene UBE3A
two copies of the SNRPN gene and no UBE3A gene functioning
symptoms of angelman syndrome
Severe intellectual disability
seizures
Puppet like posture of limbs
What basepairs are repeated in fragile X syndrome
CGG
What basepairs are repeated in Friedrich ataxia
GAA
What basepairs are repeated in HD
CAG
What basepairs are repeated in Myotonic
dystrophy
CTG
What is anticipation?
The larger the repeat, the greater is the chance for it to be unstable and it tends to expand from one generation to the next
What diseases are anticipation found?
- HD
- myotonic dystrophy
- Fragile X syndrome
What gene mutation leads to fragile X syndrome
FMR1
symptoms of fragile X syndrome
Intellectual disability learning difficulties prominent ears elongated face macro orchidism
females are less impacted
shows anticipation
more repeats = increased severity
Fragile X syndrome diagnostic test
southern blot analysis
