Imprinting Flashcards
Imprinting Definition
Turn off
Imprinting (overall)
In genome = have maternal and paternal chrosmome –> some genes express mom copy and some gene express dad copy
Means = have monoalleleic expression
Effect of Imprinting
Leads to monoallelic expression
Off in mom vs. Off in dad
Off in mom = maternal imprinting
Off in dad = Paternal imprinting
Never have case where both are turned off
Genetic Imprinting vs. Psycology Imprinting
THEY are different
Imprinting
Biologic Phenomena in which certain genes are expressed in a parent of orgin specific manner due to epigenetic modifications
Imprinted gene
Genes are turned off on chromsome
Materna vs Paternal Imprinting
Genes turned off in chromosome inherited by mother = Maternally Imprinted
- Epigenetic modification that silened experession from chromsome from mom – rely on Expression of gene from paternally inherited
Genes turned off in chromsome inherited from father = Paternally Imprinted
How are imprinting patterns established
Imprinting patterns are estblished by DNA methylation
Cytosine –> Meth-Cytosine
- Methyl never occurs on Lone C (occurs at CpG)
How does DNA methylation occur
Find Methyl on S-Adenosine-M
CpG sites clustering
CpG sites cluster in genome – Large number of methylated CpG sequences together = CpG Island
CpG Island
300 - 3,000 BP and >50% of sequences as CpG Sites
- Island tends to be near promoter for genes
- CpG near promoter = inhibit gene expression
- Any subset of CpG = can be imprinted
When are imprinting patterns established
Imprinting patterns are estblished during Gametogenetisis
Imprinting During Gametogenesis
Offspring undergo meosis = earase Imprinting pattern and replace with pattern specific to male or female
Male = erase and replace with paternal pattern
Female = earse and replace based on maternally imprinted pattern
Regardless of orginal methylation patterns – new patterns are established in gametes
Mendelian ratios + Imprinting
Maternal and Paternal are passed in mendelian ratios to offspring regardless of orginal methylation pattern
Egg vs. Sperm
Egg = have chromosomes with maternal CH3 pattern
Sperm = Have paternal CH3 pattern
When unit = can form female or male offspring –> each offspring contains a Maternal (Witg maternal imprinting) and Paternal (With paternal imprinting) chromsome
Imprinting pattern in male vs. female offspring
Imprinting pattern are NOT different between male and female offspring
Different in mom vs. dad
Imprinting example
IGF2 Growth factor = maternally imprinted
Receptor = Paternally imprinted
IMAGE – shows which alleles are methylated/ on and off
- IGF2 will be off in mom chromsomes (methylated)
- receptor = Off in dad chromosome = methylated
Imprinted genes + Transcription
Imprinted genes are transcriptionally silent – gene expression comes from non-imprinted chromsome
Growth Factor vs. Recptor size
Expression level + Phenotypes
GF = receptor –> Normal size mouse
GF > Receptor –> Largeer mice
GF < Receotore –> Smaller mice
Answer: Father
GF = Maternaly imprinted
WT copy is off and we rely on the other copy BUT the other copy is mutated = no GF –> have no GF and have more receptoe = end smaller
- If mutated copy was imprinted (if inherited myuated from mom) = kids would be fine
- Maternal is off because GF is maternally imprinted
Image of Maternal vs. Patternal imprinted
GF = Maternal imoprinted
Receptor = Paternally imprinted
Imprinting in gametogensis
Imprinting patterns are establoshed in a sex specific manner
First – imprinting patterns are earased during the first steps of meiosis
Second – Imprinting patterns are reastblished during later steps of meiosis (done in way specific to sex)
Passing down imprinted genes
Methylated if maternally imprinted genes in female
Methylate if paternally imprinted gene in males
Image – A1 and A2 = imrpinted because that gene is maternally imprint = imprint in ALL egg even in the A2 alelle from Paternal
Answer: Oogensis
Imprinting in Oogenesis vs. Spermogensis
Oogensis = ALL egg get maternal imprinting pattern
Spermogensis = ALL Sperm get paternal imprinting pattern
Answer: Larger than normal
IGF2 – have mom + dad
Receptor – have mom
GF > Receptor = larger
Tiger = have 2 GF and 2 Receptor; Lion 1:1
Paternal lion receptor = off
Have GF (from Tiger) + R (from toger) + GF (from lion but no receptor) = GF > Recptor = larger
Answer: Angelman – because get Angleman genes from neither
Paternally imprinted = Methylated/off in paternal
Answer: Prader Willi
No PW gene (methylaed/off in mom and deleted in dad) = get PW
***Lack of gene = get syndorme
Answer: C
In generation 1
- Know one A1 is methylated in mom because got one allele from mom that must be methylated
- Know A1 is methylated in dad because he has the trait = express A2 = A1 is methylated
Example:
Have carrier mom in generation 1 (mom = AA’)
- Know mom is carrier - so if A’ is what leads to trait themn A’ must be silenced because she does not have the trait
- Mom passes A’ allels to her son and her second dauhter - because both are carriers but not expressing the trait = know they have to be silenced copy of the alelle
Carrier son in genertion has a son that is affected
- Son must have inherited the A’ alelle leading to the trait and that allele must be expressed
- Carrier daughter in second generation that doesn’t have the trait has 2 children that are carriers –> these children muct have inherited the same A’ alelle and teh A’ must be silenced or they would have phenotype
Overall: have a female that passes down silenced copies of A’ and her daughter also passes silenced copies = consistent with maternal imprinting AND son who is carrier who does not imrpint allele so wehn pass down allele it is expressed
Paternal Imprinting
Have a carrier male in genration 1 (A’) – A’ must be methylated –> passed A’ to two offspring and each are Methylated
The son in generation 2 passes down A’ to one of his offspring –> offspring is also affected = the offspring inherite methylated
Carrier daughter in genration 2 passes A’ allele in mendelian ratios to her offspring –> because this is paternally imprinted the A’ allele passed on by female is not imprinted = active = both offspring in genration 3 are affected
Patterns of Phenotype from maternal imprinting
Have an affected female with A’ allele that leads to phenotype – she expresses phenotype = know A’ is active in ger = her copy of A must be methylated; patner is AA (one copy is methylated)
Have 4 kids – mendelian ratios apply
- Affected female passes A’ to 2 offpsirng and passes A top 2 offspring –> because maternally imprinted gene = all alles that she passes down is methylated and silenced ( A and A’ she passes down - all silenced)
Offspring in generation 2 have a silenced copy of maternally inherited allele - even though have A’ its is silenced
- A’ in second generation will be phenotypically normal because methylaed = carriers
- Father in generation one - passes A to all offspring - because maternally imprinted he will pass down active copies of A
In generation 3:
- carrier female pass her A’ allele to half of her offspring and her WT A to half of offspring
- Maternally imprinted alelle = she will sielnce each copy of alelele that she passes down
- 1/2 offspring have A’ – they are both silenced = carriers
- All 4 children will be normal while 2 carriers
- carrier male in generation 2 gives A’ alelle to 1/2 of his offspring and A to other half –> maternally imprinted alelle so all of his contrubition remain active; his Wt partner gives A allele that will be silenced because maternally imprinted – offspring that inherit A’ alelele = express diases alelle = diseased
- Other two offspring are phenotyoically WT and genotypically WT
- female AA pass down impronted copyt of A to each offspring – partner will pass down active A locus
- Wt male offspring will pass down Active A alelles while his partner will pass down imrointed copy of her allele
***For maternaly imrpinted genes – feamkes always pass down silencec copies of alelles wheras males will pass down activce copies of alelles
Example - Paternal Imprinting
Patenrally imrpted green A = silenced in the next generation
A and A’ alleles that are inherited in Generation 2 = active
- Indiviual with A’ express disease phenotype
Patenral imprinting means that the males will pass down silences cpopies of their alleles to their offspring
Indiviuals with A’ allele from mom = express disease phenotyoe
Offspring that get A’ allele =from affected foather have a silenced opy of diseased allele = they will be cacriers
