Angelman syndrome A. A defect on which 15th chromosome, maternal or paternal, le
ID: 77991 • Letter: A
Question
Angelman syndrome
A. A defect on which 15th chromosome, maternal or paternal, leads to Angelman syndrome? A defect on the other copy leads to which syndrome?
B. How is the paternal copy of Ube3a silenced?
C. What are the different subtypes of Angelmans’ syndrome?
D. Explain the results of the methylation assay if somebody has Angelman’s syndrome
E. If a FISH analysis comes back abnormal, then what defect has caused AS in that individual?
F. How does Topotecan/Irinotecan work to turn on the paternal copy ofUbe3a?
G. What is the other approach being used to activate gene expression of Ube3a?
Explanation / Answer
(A) The Prader-Willi syndrome is caused by loss of active gene in a specific part of the chromosome 15 i.e. tge 15q11-q13 region. When the sequence is deletes frm the paternal chromosone, the genes are active on paternal copy and inactive on the maternal copy.
(b) Silencing of the paternal copy of Ube3a gene:
The evaluation of the phenotypic effects can be done by the activation of silenced paternal alleles of Ube3a gene by depleting its antisense RNA i.e. the Ube3a-ATS in mice. Prematuretermination of this antisense RNA by poly(A) cassette insertion activatesexpression of Ube3a from paternal chromosome and ameliorates many disease relates symptoms.
(c) Subtypes of Angleman Syndrome:
(1) deletion subtype: 70% of the individuals havea deletion of maternal copy of 15q 11.2 - q13 sequence. most delet ons are of same size however they may be grouped in two types class 1 and class 2. Class 1 deletions are larger than class 2 deletions.
(2) Unipaerntal disomy subtype: in 7% of the individuals; both the copies are inherited from tge father and maternak copy is missing.
(3) Ipairing defect:
In 3% of the individuals. The individuals inherit a copy of chromosome15 from each parent but region q11-q13 inherited from the mother is not expressed.
(4) Ube3a mutation subtype: mutation of Ube3a gene lying with 15q11-q13 sequence. The loss of I've a functin acuses the syndrome.
(d) Methylation assay:
Most useful diagnostic test of AS. There are3 major loci i.e. Znf127, PW71 and 5' SNRPN. The specimen to be examined are obtained from anmiotcentesis and chorionic villus sampling. Correct parental diagnosis are obtained in 24 out of 24 samples using 5' SNRPNs, 4 from ZNF127 and 10 using PW71 locus. The data indicates that although the SMS methylatin imprints of ZNF127 and 5' SNRPN are present in brain.
I can't answer the last 3 parts of this question because i don't want to give you incomplete knowledge. SORRY.