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

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

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


What is hypothyroidism?

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


What is SNRPN?

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


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


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


Describe the symptoms of Angelman Syndrome

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


What is the difference between PWS and AS?

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


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)


What is the cause of Angelman Syndrome?

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


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


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

Large tongue, larger birth weight, rhabdomyosarcoma


What is the cause of Beckwith-Wiedemann syndrome?

Paternal uniparental disomy of chromosome 11


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


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


What mechanisms are involved in imprinting?

DNA methylation and histone modification


Describe the process of DNA methylation

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


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)


Define epigenetics

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


Describe what is meant by 'uniparental disomy'

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


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


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.


What does non-consanguineous mean?

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


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


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

q11-13 region of chromosome 15


What is the significance of the SNRPN gene?

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


How are histones involved in gene expression?

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


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

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


What is the role of histone deacetylases (HDAC)?

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


What are the characteristics of an imprinted gene?

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


What indicates transcriptional competence?

Binding of transcription complex


What are the characteristics of a transcriptionally active gene?

Opening of chromatin by acetylation and there is demethylation


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)


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