Lecture 8

Question 1

what are the 5 atypical patterns of inheritance

Answer 1

1. genetic/ genomic imprinting
2. uniparental disomy
3. anticipation
4. mosaicism
5. mitochondrial inheritance

Question 2

Genetic Imprinting

Answer 2

some parts of the human genome are imprinted to show that they originate from their father or mother

Question 3

what are imprinted regions in the human genome

Answer 3

areas of chromosomes 6, 7, 11, 14 and 15

Question 4

explain what is an imprinting region

Answer 4

a region where multiple imprinted genes are in close proximity to each other in clusters or domains within the genome

Question 5

if a person loses the 15q11 that they inherited from their normal father what will they develop

Answer 5

Prader Willi syndrome

Question 6

if a person loses the 15q11 they inherited from their normal mother they will develop

Answer 6

Angleman’s syndrome

Question 7

what are the clinical features of angelman syndrome

Answer 7

• Developmental delay
• Intellectual disability
• Lack of speech
• Unsteady or jerky movements
• Happy demeanour, fits of laughter
• Seizures

Question 8

what are the clinical features of Prade - Willi Syndrome

Answer 8

• small hands and feet
• obesity
• hypotonia ( weak muscles)
• hyperphagia (insatiable appetite)
• delayed sexual development

Question 9

how are two clinically different disorders caused by the same chromosome 15q11 deletion

Answer 9

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

Question 10

uniparental disomy

Answer 10

individual inherits both copies of a chromosome from one parent

Question 11

uniparental isodisomy

Answer 11

two identical chromosome both from the same parent

Question 12

uniparental heterodisomy

Answer 12

two different chromosomes both from the same parent

Question 13

how can an isodisomic chromosome cause disease

Answer 13

can cause disease if isodisomy chromosome has an autosomal recessive disease mutation

Question 14

how can a uniparental disomy cause disease

Answer 14

can cause disease if the uniparental disomy occurs in an imprinted chromosomal region

Question 15

what is the initial event in uniparental disomy

Answer 15

a non disjunction: when the chromosomes do not seperate properly during meisos

Question 16

trisomic embryo

Answer 16

an embryo which has an additional copy of one embryo

Question 17

Prader Willi syndrome caused by uniparental disomy

Answer 17

can occur if a baby has uniparental disomy for 2 maternal chromosome 15s. there is no parental copy of SNPRN

Question 18

Angelman syndrome caused by uniparental Disomy

Answer 18

can occur if a baby has two parental chromosome 15s. there is no maternal copy of UBE3A

Question 19

Genetic Anticipation

Answer 19

the manifestation of a genetic disorder at an earlier age or with severity in succeeding generation

Question 20

why does the severity of the genetic disorder increase generation after generation

Answer 20

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

Question 21

Myotonic dystrophy - Steinert’s disease

Answer 21

autosomal dominant disorder with marked genetic anticipation - unstable triple repeat disorder

Question 22

mild late onset form of Steinert’s disease

Answer 22

mild muscle weakness
cataracts

Question 23

typical form of Steinert’s disease

Answer 23

muscle weakness
cardiomyopathy
cataracts
frontal hair loss

Question 24

Childhood/infantile form of Steinert’s disease

Answer 24

profound muscle weakness
global developmental delay

Question 25

molecular diagnostic detection of expanded triplet repeat disorders

Answer 25

detection by southern blot for larger expansions
Detection by PCR for smaller expansions /

Question 26

fragile X syndrome

Answer 26

2nd most common genetic cause of learning disability after down syndrome

• affects males more then females
• easier to recognize in older men

Question 27

fragile X symptoms in affected males

Answer 27

learning disability,
usually special education,
often behavior disturbance

Question 28

fragile X syndrome symptoms in adult males

Answer 28

tall
large ears
long face
loose joints

Question 29

Fragile X syndrome clinical genetics

Answer 29

only carrier females have affected children

Question 30

mosaicism

Answer 30

a mixture of 2 genetically different cell lines in a person derived from a single embryo

Question 31

somatic mosaicism

Answer 31

two different cell lines exist in several parts of the body

Question 32

gonadal mosaicism

Answer 32

two different cell lines present in only ovary or testis

Question 33

what is the most common chromosomal mosaicism disorder

Answer 33

Turner Syndrome

Question 34

symptoms of tuners syndrome

Answer 34

• short stature
• webbed neck
• delayed or absent puberty

Question 35

mitochondrial inheritance as an atypical pattern of inheritance

Answer 35

mutations can occur in the mitochondrial genome independent of the cell mitosis

some mitochondrial mutations can be inherited

Question 36

heteroplasmy

Answer 36

the mixture of normal and mutant mitochondria in a cell

Question 37

examples of mitochondrial inherited disease

Answer 37

Leber’s hereditary optic neuropathy
- onset visual loss in late teens, remission and then progressive visual loss

MELAS

deafness