Lecture 8 Flashcards
what are the 5 atypical patterns of inheritance
- genetic/ genomic imprinting
- uniparental disomy
- anticipation
- mosaicism
- mitochondrial inheritance
Genetic Imprinting
some parts of the human genome are imprinted to show that they originate from their father or mother
what are imprinted regions in the human genome
areas of chromosomes 6, 7, 11, 14 and 15
explain what is an imprinting region
a region where multiple imprinted genes are in close proximity to each other in clusters or domains within the genome
if a person loses the 15q11 that they inherited from their normal father what will they develop
Prader Willi syndrome
if a person loses the 15q11 they inherited from their normal mother they will develop
Angleman’s syndrome
what are the clinical features of angelman syndrome
- Developmental delay
- Intellectual disability
- Lack of speech
- Unsteady or jerky movements
- Happy demeanour, fits of laughter
- Seizures
what are the clinical features of Prade - Willi Syndrome
- small hands and feet
- obesity
- hypotonia ( weak muscles)
- hyperphagia (insatiable appetite)
- delayed sexual development
how are two clinically different disorders caused by the same chromosome 15q11 deletion
it depends on whether the deletion affects the maternal or parental copy of chromosome 15q11 because
the maternal copy expresses UEB3A and the absence of this leads to Angelman syndrome
the paternal copy expresses SNPRN and the absence of this causes Prader-Willi Syndrome
uniparental disomy
individual inherits both copies of a chromosome from one parent
uniparental isodisomy
two identical chromosome both from the same parent
uniparental heterodisomy
two different chromosomes both from the same parent
how can an isodisomic chromosome cause disease
can cause disease if isodisomy chromosome has an autosomal recessive disease mutation
how can a uniparental disomy cause disease
can cause disease if the uniparental disomy occurs in an imprinted chromosomal region
what is the initial event in uniparental disomy
a non disjunction: when the chromosomes do not seperate properly during meisos
trisomic embryo
an embryo which has an additional copy of one embryo
Prader Willi syndrome caused by uniparental disomy
can occur if a baby has uniparental disomy for 2 maternal chromosome 15s. there is no parental copy of SNPRN
Angelman syndrome caused by uniparental Disomy
can occur if a baby has two parental chromosome 15s. there is no maternal copy of UBE3A
Genetic Anticipation
the manifestation of a genetic disorder at an earlier age or with severity in succeeding generation
why does the severity of the genetic disorder increase generation after generation
disorders are caused by unstable trinucleotide repeat expansions in specific genes.
As the number of trinucleotide repeats increases beyond a certain threshold, the severity of the disorder may increase at symptoms may manifest at an earlier age
Myotonic dystrophy - Steinert’s disease
autosomal dominant disorder with marked genetic anticipation - unstable triple repeat disorder
mild late onset form of Steinert’s disease
mild muscle weakness
cataracts
typical form of Steinert’s disease
muscle weakness
cardiomyopathy
cataracts
frontal hair loss
Childhood/infantile form of Steinert’s disease
profound muscle weakness
global developmental delay