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
Maternal vs. Patternal imprinted in gametogensis
Maternal imprinting – genes that are methylated/silenced during oogensis (egg cells)
- All eggs get the same imprinting pattern
Patneral imprinting – Genes are truned off during spermogensis (sperm cells)
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)
Imprinting pattern in cells
Pattern in all cells in body is the same until go to gameteogensis
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
Imprinting in gametogensis (overall)
All of the gametes form an indiviuals receive the same imprinting pattern
The pattern depends on the sec of the person creating the gametes
All members of the same sex produce the same imprinting patterns
Imprinting is indepentdent of the alleles
Are all genes imprinted
NOT all genes are imprinted
Only 1% of mammales and flowering plants
Where has genomic imprinting been identified
Genomic imprinting has been identified in mammals + insects + flowering plants
1% of mammalian genes are imprinted
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
Hypothesis for why imprinting occurs?
Parental conflict
dad = wants to put all resources in kids to grow big and strong = use all maternal resources –> turn off receptor = have more GF hormone than receptor
Mom = Wants kids to grow big enough to be healthy BUT leave some resources for mom and future kids = turn off hormone and turn receptor on
Imprinting Disorder
- Prader Willi
- Angelman’s syndorme
Prader Willi
Maternally Imprinted –> rely on expression of paternal
- Occurs when have problems with paternal PW genes
Prader willi + Angleman’s syndrome
Linked to the same imprinted region on Chromsome 15
Some silence in egg = maternally imprinted
Some silence in sperm= paternally imprinted
Imprinting + Development
Imprinting is required for normal development
Individuals normally have one active copy of imprinted gene
If have improper imprinting = leads to individual with 2 active copies or 2 inactive copies = develop abnormalities or cancer
Angleman syndrome
Patenrally imprinted = Transcript is silenced from paternal allele –> caused when have probelms with maternal Angelman genes
Cause of PW and Angleman
A common cause of PWS and AS is a de novo delation of a region of Chromosome 15 that removes both the PW genes and teh AS genes
- Mutation occurs during gamnetogensis
Delection occurs in oogensis –> PW genes are fine because have paternal; chrosmome BUT the genes for Angelman are off on the paternal and rely on the maternal = gene is missing if have deltion in oogensis = result of deltion is Angleman
Deletion in Spermogensis = Angelman genes are fine (expressed on maternal) BUT PW are silenced in maternal and paternal are missing = get PW syndrome
Inheritance of the same deletion can lead to different disease depending on the parent or origin
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
Hypothesis for Reason for Imprinting (Panapto)
Overall: Parental Conflict
Males want offspring tp use all maternal resources to get as big as possible (not interested in long term success of partner because can always find another partner)
- Accomplish their goals by passing an active copy of Growth factor and turn off receptor – receptor nuetralizes the effect of growth factor
Females have a vested interest in having healthy kids but they want children to leave some resources for them and future kids
- Accomplish goals by turning off growth hormone (GF is imprinted and recptor is on)
IGF2 GF is maternally imprinted
Receptor = Paternally imprinted
In combination = monoalleleic expression of both genes –> 1:1 ratio
Expression after Imprinting
In combination of both parents = mono-allelic expression of both genes -
Expression of GF and recptor
Under most circumstances IGF2 is maternally imprinted and receptor is paternally imprinted = 1:1 expression ratio of the hormone and receptor
- When have equal expression = get normal size individuals
- GF > recptor = get larger size
- GF < Receptor = get smaller size
Are imprinting patterns conserved between animals
NO imprinting patters are not necessarily conserved between all animals
Example:
Tigers = do not imprint GF or receptor
Lions = Maternally imprint GF and paternally imprint recepyor
Female Tiger + Male lion = Make liger
- Female tiger = privides gametes with both GF and recprtor on and lion gives gametes where GF is turned on and the receptor is off
END = 2 copies of GF and 1 copy of receptor = GF > recptor = larger
Effect of monoalleleic expression
Means that there is no backup allele = imprinted genes are particularly sensitive to envirnmental stress
- Additional epigentic modifications may reduce gene expression leading to phenotyoe
- Envirnmnetal stessed
Effect of envirnmental stressors
Environmental stressors are known to interfere with DNA methyltransferases involved in imprinting process
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
Mendelian ratios + imprinting
Mendelian Ratios should apply
Example - Mom AA’ –> Should gives A to 1/2 offspring and A’ to 1/2 offspring – get 50% A and 50% A’
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
Imprinting Summary
Imprinting genes are those that are silenced (methylated) during gametogensis
Imrpinting patterns are specific to oofgenesis/spermogensis
Imprints are earased then re-established during gametogenesis
Imrpinting leads to monoalleleic expression
Imrpinted genes are senistive to envirnmental modifications
Imrpting may be the result of gentic conflict between female and male
