Imprinting disorders Flashcards
What usually happens in diploid species if defective copy of gene is inherited? and in what circumstance is this not the case?
Usually in diploid species (like humans), if a defective copy of a gene is inherited there is a second (functioning) copy from the other parent that can compensate for this loss
This is not true of imprinted genes
Even though there are two copies of the gene, as only one copy is expressed, mutations affecting this copy will result in disease.
So what would happens if two defective imprinted genes were to be inherited?
Situations that result in both copies of a gene being silenced will also lead to expression of the disease.
How is Beckwith-Weidermann syndrome caused?
An imprinted region of the human genome that contains Ifg2 (the human homologue of IGF-II mouse gene) causes an inherited disease: Beckwith-Weidemann syndrome
Hypermethylation
SIlver-Russell syndrome
hypomethylations of chromosome 15
State the database for genetic diseases in humans?
Online Mandelian Inheritance in Man (OMIM)
What is Beckwith-Weidermann syndrome?
A pediatric overgrowth disorder invovling a predisposition to tumour development.
Family study the showed paternal inheritance of BWS.
Paternal UPD causes people to have two active copies of paternally inherited genes rather than one active copy from the father and one inactive copy from the mother.
The pedigree of the family under investigation is illustrated in fig 1. Two phenotypically normal half sisters (patients II.2 and II.8) who have a common father (I.2) have each produced three offspring with the characteristic clinical manifestations of BWS. Two affected boys (III.2 and III.5) died in early infancy. They showed conclusive evidence of the disorder at necropsy. The remaining five affected relatives are all female, the oldest of whom (III.4) has had a daughter with BWS.
Learn the table given in slides.
CHosen disorder
Clinical defects of chosen disorder
Chromosome where gene is located in chosen disorder
Referecne of chosen disorder?
What are the genetic mechanisms of PWS - draw them out.
Deletion of the paternal Prader-Willi region (70%)
Maternal unipaternal disomy 15 (25%)
Mutations in the imprinting control region (ICR)
Translocation that separates the ICR from the Prader-Willi region.
Self-assessment questions.
Briefly outline the experiment(s) from the 1980s that demonstrated that the paternal and maternal genomes are not equivalent in mice
Give an example of a paternal imprinted gene (and a disease associated with that gene)
Give an example of a maternally imprinted gene (and disease)
Sketch out two different ways that Prader-Willi Syndrome can occur. Indicate which is the most common.
The imprinting cycle
Epigenetic marks are erased during gametogenesis
After fertilisation the epigenetic marks are replaced with the appropriate epigenetic signature for the sex of the developing embryo (which will always be different from one of its parents!)
