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
molecular diagnostic detection of expanded triplet repeat disorders
detection by southern blot for larger expansions
Detection by PCR for smaller expansions /
fragile X syndrome
2nd most common genetic cause of learning disability after down syndrome
- affects males more then females
- easier to recognize in older men
fragile X symptoms in affected males
learning disability,
usually special education,
often behavior disturbance
fragile X syndrome symptoms in adult males
tall
large ears
long face
loose joints
Fragile X syndrome clinical genetics
only carrier females have affected children
mosaicism
a mixture of 2 genetically different cell lines in a person derived from a single embryo
somatic mosaicism
two different cell lines exist in several parts of the body
gonadal mosaicism
two different cell lines present in only ovary or testis
what is the most common chromosomal mosaicism disorder
Turner Syndrome
symptoms of tuners syndrome
- short stature
- webbed neck
- delayed or absent puberty
mitochondrial inheritance as an atypical pattern of inheritance
mutations can occur in the mitochondrial genome independent of the cell mitosis
some mitochondrial mutations can be inherited
heteroplasmy
the mixture of normal and mutant mitochondria in a cell
examples of mitochondrial inherited disease
Leber’s hereditary optic neuropathy
- onset visual loss in late teens, remission and then progressive visual loss
MELAS
deafness
