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)
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)