Imprinting in mammals Flashcards

1
Q

What is genetic imprinting?

A

epigenetic phenomenon that causes genes to be expressed or not depending on whether they are inherited from the female or male parent

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2
Q

Maternal imprinting

A

gene from mother is transcriptionally silent
phenotype governed by paternal allele

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3
Q

Paternal imprinting

A

gene from father is transcriptionally silent
phenotype governed by maternal allele

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4
Q

What was the first evidence of genetic imprinting?

A

enucleated mice oocytes → control diploids + gynogenetic diploids implanted into mice
control → embryo viable
bimaternal → embryo inviable

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5
Q

Transmission of IGF-II mutation through male germline

A

heterozygous offpsring that are growth deficient

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6
Q

Transmission of IGF-II mutation through female germline

A

heterozygous offspring that are phenotypically normal

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7
Q

What did studies on IGF-II imprinting in mice show?

A

phenotype depends on the gamete contributing the mutation
paternal + maternal members of some autosomal gene pairs are functionally non-equivalent

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8
Q

How was it proven that only the paternal IGF-II allele was expressed?

A

nuclease protection + in situ hybridisation

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9
Q

How have bimaternal mice been generated?

A

stem cells extracted + cultured in medium that causes global DNA methylation
paternally imprinted loci deleted using CRIPSR

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10
Q

Bimaternal vs bipaternal reproduction in mice

A

bimaternal a lot easier to produce than paternal
paternal requires more steps + deletion of more imprinted genes required
paternal mice generated but died before adulthood

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11
Q

Examples of imprinting disorders

A

Beckwith-Weidemann syndrome
Prader-Willi syndrome
Angelman syndrome

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12
Q

Beckwith-Weidemann syndrome

A

large birth size
predisposition to tumours

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13
Q

Prader-Willi syndrome

A

obesity
behaviour + cognitive problems
deficiencies in sexual development

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14
Q

Angelman syndrome

A

developmental deficiencies
sleep disorders
seizures
happy disposition

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15
Q

What is BWS caused by?

A

abnormal regulation of genes on paternal 11p15.5 chromosome
leads to hypomethylation of ICR

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16
Q

What is ICR?

A

imprinting control region (1 and 2)
1 controls expression of IGF2 + H19 genes
2 controls expression of CDKN1C + KCNQ1

17
Q

What is PWS caused by?

A

abnormal regulation of genes on paternal 15q11-q13 chromosome
maternal uniparental disomy

18
Q

What is angelman syndrome caused by?

A

abnormal regulation of genes on maternal 15q11-13 chromosome
deletion of PW region
paternal uniparental disomy

19
Q

What does uniparental disomy mean?

A

maternal- inheritance of both copies of a chromosome from the mother
paternal- both from father
underlies many imprinting disorders

20
Q

What is the molecular basis of gene imprinting?

A

epigenetic regulation
methylation → gene silencing
acetylation → gene stimulation

21
Q

Euchromatin

A

transcriptionally active
chromatin loosely coiled
HAT targets H3 tail
stimulates nucleosome accessibility

22
Q

Heterochromatin

A

transcriptionally repressed
chromatin tightly coiled
KMTs methylate H3 tail
impairs nucleosome accessibility

23
Q

What group of enzymes reverse histone acetylation?

A

histone deacetylases (HDACs)