FunMed: PBL 3 (Imprinting - Prader Willi Syndrome) Flashcards Preview

(YEAR 1) PBLs > FunMed: PBL 3 (Imprinting - Prader Willi Syndrome) > Flashcards

Flashcards in FunMed: PBL 3 (Imprinting - Prader Willi Syndrome) Deck (33):
1

Define genomic imprinting

Epigenetic phenomenon where certain genes are expressed in a parent-of-origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. Silent gene is methylated

2

What is hypothyroidism?

Abnormally low activity of thyroid gland --> retardation of growth and mental development in children and adults

3

What is SNRPN?

Small nuclear ribonucleoprotein-associated protein N; plays a role in pre-mRNA processing

4

What is a chromosomal microarray?

a set of DNA sequences representing the entire set of genes of an organism, arranged in a grid pattern and used in genetic testing

5

Describe the symptoms of Prader Willi Syndrome

Birth: hypotonia and poor sucking reflex due to lack of muscle tone
Childhood: developmental defects, excessive sleeping, overeating and delayed puberty
Aduthood: hypogonadism and prone to diabetes

6

Describe the symptoms of Angelman Syndrome

"Happy puppet syndrome" - intellectual and developmental disability, speech impairment, seizures, jerky movements and frequent laughter and smiling

7

What is the difference between PWS and AS?

PWS = due to imprinting/silencing of maternal chromosome
AS = imprinting/silencing of paternal chromosome

8

What is the cause of Prader Willi Syndrome?

Deletion of q11-13 region of paternal chromosome 15 OR maternal uniparental disomy (UPD) with lack of paternal chromosome 15. This syndrome occurs because there is imprinting on the maternal chromosome 15 (silencing)

9

What is the cause of Angelman Syndrome?

Deletion of q11-13 region of the maternal chromosome 15 or paternal uniparental disomy

10

What are the proposed reasons for genomic imprinting?

Ovarian time bomb theory - imprinting involved to prevent spontaneous development of unfertilised eggs
Genetic conflict hypothesis - strikes a balance between some genes e.g. paternal imprinting --> larger offspring, maternal offspring --> smaller offspring

11

What are the symptoms of Beckwith-Wiedemann (foetal overgrowth) syndrome?

Large tongue, larger birth weight, rhabdomyosarcoma

12

What is the cause of Beckwith-Wiedemann syndrome?

Paternal uniparental disomy of chromosome 11

13

What support is available to support a child with chronic illness?

Learn about illness, support group, face possibility of early death, maintain open and honest communication, share leadership and include all family members in decision making

14

What treatment is there for Prader Willi Syndrome?

No cure; speech therapy, structurelearning involvement, prevention of over-feeding and growth hormone injections (daily) to support linear growth and increase muscle mass

15

What mechanisms are involved in imprinting?

DNA methylation and histone modification

16

Describe the process of DNA methylation

Attachment of methyl (CH3) groups to the bases of DNA at cytosines that follow guanine (CpG dinucleotides)

17

Describe the process of histone modification

Histone acetyl transferases may acetylate lysine in core histones (transcriptional activation) or histone deacetylases may remove lysine residues (deactivate transcription)

18

Define epigenetics

Study of changes in organisms caused by modification of gene expression rather than alteration of genetic code itself

19

Describe what is meant by 'uniparental disomy'

Receiving two copies of a chromosome from one parent and none from the other

20

Describe how methylation-specific PCR can diagnose PWS or AS.

PCR can be conducted in SNRPN region of q11-13 region of chromosome 15:
PWS: methylation of maternal chromosome in comparison to control
AS: methylation of paternal chromosome in comparison to control

21

What disease can become more prevalent in children whose parents are consanguineous?

Autosomal recessive genetic disorders can become manifest as two heterozygotes can generate a homozygous child.

22

What does non-consanguineous mean?

A union between two individuals who are not related as second cousins or closer

23

Why may there be increased stress in a family where there is a child with chronic illness?

Financial concerns (treatment expense), parent unable to work or relax (constant care), distress from seeing child in pain/suffering, sense of no hope or entrapment if there is no cure

24

Which chromosome is involved in causing both Prader Willi and Angelman syndromes?

q11-13 region of chromosome 15

25

What is the significance of the SNRPN gene?

It's the region which is affected by methylation to produce either AS or PWS

26

How are histones involved in gene expression?

Control coiling and uncoiling of DNA to allow transcription (or not)

27

What is the role of histone acetyl transferases (HAT)?

Acetylate the lysine residues in core histones --> less compact, transcriptionally active chromatin

28

What is the role of histone deacetylases (HDAC)?

Remove acetyl groups from lysine residues in core histones --> condensed, transcriptionally silences chromatin

29

What are the characteristics of an imprinted gene?

CpG islands, nucleosomal condensation (due to deacetylation) and methylation

30

What indicates transcriptional competence?

Binding of transcription complex

31

What are the characteristics of a transcriptionally active gene?

Opening of chromatin by acetylation and there is demethylation

32

How is methylation involved in germ cell development?

Primordial germ cells are demethylated (activated) early in development, and sperm and oocytes are remethylated (prevent spontaneous development)

33

How does methylation-specific PCR work?

Bisulfite is added to a sample of DNA from an individual, and the non-methylated (active)cytosine (C) bases will be converted to uracil, and after PCR will become thymine (T) whereas methylated (transcriptionally active) C is unchanged, and this can be analysed