Lecture 6: Imprinting and Epigenetics Flashcards
PWS and AS are similar in what way?
Same interstitial microdeletion on prox long arm C 15, but completely diff phenotypes. FISH gives same result, a 15q deletion.
Describe PWS patients
Can get obese, DD but do well in special ed, temper, small hands and feet
Describe AS patients
Severely MR’d, hyperactivity, short stature, microcephaly, seizures, ataxia.
In PWS, the deletion is present on the chromosome inherited from mom or dad? In AS?
PWS = from dad, AS = from mom.
PWS appears to be due to a lack of the paternal contribution of the genes in one region of C 15 (same deal with AS but due to lack of maternal contrib), so what else can give PWS?
Maternal disomy.
Inheritance of a chromosome or chromosomes from 1 parent to the exclusion of the other parent
Uniparental disomy (can’t be detected by std karyo cuz the homologs look alike, detmntion of UPD requires molec probe tech). UPD can be heterodisomic or isodisomic. Isodisomy is the dup of 1 chrom from one parent. Uniparental heterodisomy generally results from meiotic ndj errors.
The only solution to a monosomy that’ll result from a ndj error is to do what to the one existing chrom? This results in uniparental isodisomy.
Duplicate it.
A child shown to have 2 copies of the deltaF508 mutation, paternity is as stated, and only one parent has the mutation, what the hell is going on? You expect examination of both the child’s 7’s reveal he/she is [blank] at all loci on the 7, consistent with [blank]?
Homozygous, Uniparental isodisomy.
Reciprocal to the duplication rescue following ndj to ensure disomy (albeit uniparental), the trisomy can be corrected by random loss of one chrom to give biparental heterodisomy (desired outcome) in what freq, and uniparental heterodisomy in what freq?
2/3, 1/3.
The differential modification of the maternal
and paternal genetic contributions to the
zygote resulting in the differential
expression of parental alleles during
development and in the adult. Recall the t13,14Rob and AW/PWS cases in the notes, these are examples.
Imprinting
What is imprinting usually assocd with? Can it be diff based on sex?
Methylation of cytosine residues of the DNA, which is an epigenetic modification. Yeppers.
How long does imprinting last and when does change occur?
Lasts one generation, can be rewritten each time cells go though meiosis.
What is the third mechanism by which PWS can be caused in addition to a deletion of the paternal 15 and UPD, all three of which result in only active genes being maternal in origin?
An imprinting error, where the complement is comprised of one chrom from mom and dad, but the paternal chrom has a maternal imprint resulting in functionally only maternal alleles.
The neurodevelopmental disorder Rett Syndrome is linked to mutations in the MECP2 txn factor. Disease severity is linked to X-inactivation. How so? Which indiv’s will be more or less severely affected?
MECP2 is located on the distal long arm of the X chrom, so it’s subject to X-inact. Heterozygous indiv’s will be more severely affected if the mutation is present on the active X in the majority of cells.
-The study of heritable changes in gene function that are
not caused by change in the DNA sequence
-Modification of transcription (or transl) that alters gene expression
and thus phenotype
-This is a normal process required for “normal” cell function
-Change in epigenetic effects can result in up- or down-
regulation of genes and this can result in disease.
Epigenetics
