Epigenetic effects; Genome imprinting

Question 1

Genomic Imprinting

Answer 1

expression of some genes depends on parental origin of the gene caused by different epigenetic modifications

Question 2

Epigenetic

Answer 2

change in gene expression without change in DNA sequence

Question 3

Parthenogenesis

Answer 3

form of asexual reproduction where development of embryos occurs without fertilization by a male, they develop from female cells

found naturally in some invertebrate animal species and some vertebrates (fish)

no known cases of naturally occuring mammalian parthenogenesisi in the wild

induced parthenogenesis in mice and monkeys results in malformation

Question 4

Teratomas

Answer 4

3 germ layers
uniparental embryoes
maternal contribution

Question 5

Hydatidiform moles

Answer 5

trophoboblasts
androgenetic constitution
the paternal contribution is important

Question 6

imprinted genes influence

Answer 6

transfer of nutrients to the fetus and the newborn from the mother and affect growth in the womb and behaviour after birth

Question 7

duplication on chromosome 7 results:

Answer 7

maternal duplication: small placenta and embryoo

paternal duplication: giant placenta and embryo

Question 8

Prader Willi Syndrome causes

Answer 8

deletion on chromosome 15
Maternal uniparental disomy
wrong imprinting

Question 9

Angelman Syndrome causes

Answer 9

deletion on chromosome 15
paternal uniparental disomy
wrong imprinitng

Question 10

special of c15

Answer 10

identical genetic change may result different clinical phenotypes depending on the parental origin of alteration

Question 11

Angelman Syndrome

Answer 11

Gene- UBE3A- ubiquitin ligase
in brain only maternal copy is active, paternal inactive

loss of maternal copy by maternal gene mutation, translocation, deletion, Paternal disomy

developmental delay, severe speech impairment, movement or balance disorder, hypermotoric behaviour, frequent laughter/ smilling
Puppet children

Question 12

Prader-Willi syndrome

Answer 12

gene- snoRNA (small nucleolar) and SNRPN
paternal copy is expressed
maternal copy is silenced
loss of paternal copy by paternal deletion, translocation, mutation
maternal disomy
hypotonia, obesity, hypogonadism

Question 13

Whats needed for proper development in embryonic and later life

Answer 13

both maternal and paternal nuclear genomes

Question 14

what is the difference between paternal and maternal genome?

Answer 14

Genomic imprinting

Question 15

genomic imprinting

Answer 15

some nuclear genes of sperm and oocyte are modified differently

called epigenetic marks or genomic imprinting which results parental origin gene expresssion

majority of imprinted genes have role in control of embryonic growth, development, and development of placenta

Question 16

usually genomic imprinting results in

Answer 16

monoallelic expression

Question 17

imprinted genes are often clustered

Answer 17

good to know

Question 18

biallelic expression

Answer 18

when both paternally and maternally expressed

Question 19

what do some germ cell genes influence

Answer 19

growth and development that are differently modified (imprinted) and these genes show parental origin expression

Question 20

Mechanisms of imprinting/epigenetics

Answer 20

Transcription- DNA methylation and Histone modifications

Posttranscription- RNA mediated gene silencing

Question 21

imprinting/epigenetics- Transcription

Answer 21

Transcription- DNA methylation (CpG islands) DNMT1, 3A, 3B
CpG islands at promotors of genes are normally unmethylated, allowing transcription. Aberrant hypermethylation leads to transcriptional inactivation

Histone modifications (acetylation, methylation, phosphorylation, ubiquitination)- effects: activation, histone deposition, euchromatic, silencing, etc

Question 22

Histone code hypothesis

Answer 22

different combinations of covalent histone tail modifications may specify the transcription of a gene = histone code

together with other modifications such as DNA methylation it is part of the epigentic code

Question 23

histone modifcations:
erasing
writing
reading

Answer 23

erasing- demethylases, deacetylases and phosphatases

writing- methyltransferases, acetyltransferases, kinases, and ubiquitin ligases

reading- proteins with domains such as bromo, chromo, tudor

Question 24

H3 funtions

Answer 24

transcriptional competence- euchromatin

inhibition of transcription- heterochromatin

inhibition of transcription- facultative heterochromatin

Question 25

interaction of DNA and histone modifications (1)

Answer 25

DNA methylation induces hisstone de-acetylation MeCP2 binds methylated DNA --> then recruits HDAC --> which de-Acetylates histones (heterochromatin/repressed euchroamtin)

Question 26

interation of DNA and histone modifications (2)

Answer 26

histone H3-K9 methylation induces DNA methylation HP1 targets methyl H3-K9 --> then recruits DNMT --> which methylates DNA

Question 27

imprinted domain of maternal 15th chromosome

Answer 27

DNA cytosine methylation Histone H3 tail methylation at lysine (H3-K9) histone deacetylating enzymes -- histone deacetylation inactive chromatin maternally expressed UBE3A

Question 28

Imprinted domain of paternal 15th chromosome

Answer 28

no DNA cytosdine 5- methylation histone H3 is lysine 4- methylation (H3-K4me) histone acetyltransferase (HAT) and H4 is acetyulated active chromatin paternally expressed SNRPN and antisene UBE3A

Question 29

main genomic imprinting mechanisms (influencing expression)

Answer 29

DNA methylation histone modifications RNA interference

Question 30

Beckwith- Wiedemann syndrome

Answer 30

``` overgrowth disorder increased risk of childhood cancer macroglossia (large tounge) macrosomia (higher birth weight and lenght) midline abdominal wall defects ear creases or ear pits neonatal hypoglycemia ``` location: 11p15 genes: IGF2 (paternal expression) H19 (maternal expression-noncoding RNA) hypermethylated maternal ICR1 paternal disomy and other mutations may cause this disroder

Question 31

silver russel syndrome

Answer 31

RSS opposite growth disroder- dwarfism maternal disomy hypomethylated paternal ICR1

Question 32

IGF2

Answer 32

insulin like growth facotr 2 major fetal growth factor paternally expressed

Question 33

H19 non coding RNA

Answer 33

mainly prenatally | maternally expressed oncogene

Question 34

Rett syndrome

Answer 34

progressive neurodegenerative disroder XD male lethality characteristic hand wringing mainly cuased by mutation of MeCP2 (Methyl-cPG-bindign protein) so there is no inhibition of transcription

Question 35

Fragile X syndrome

Answer 35

XD with incomplete penetrance ``` CGG repeats FMR-1 fragile x mental retardation protein normal: 5-55 CGGS premutation: 55-200 CGGs full mutation: over 200 CGGS ```

Question 36

uncorrect imprinting may cause

Answer 36

diseases | duh.

Question 37

how is genomic imprinting established

Answer 37

somatic cells have to retain epigenetic marks germ cells ahve to become epigenetically different from somatic cells (erase and reprogramming)

Question 38

maintance of parental marks through somatic cell division

Answer 38

DNMT1- maintenance | DNMT3a,b de novo

Question 39

genetic imprinting needs different mechanisms in somatic (retained) and germ cells (erased and sex-dependently reprogrammed)

Answer 39

ok

Question 40

conflict hypothesis

Answer 40

maternal imprinting: limits use of maternal resources by baby in utero less growh down regulates growth factors paternal imprining maximizes use of maternal resources by baby in utero more growth down regulates suppressive factors IgF2 (growth stimulation)

Question 41

possible significance of genomic imprinting

Answer 41

mothers gene keeps mothers power in store for forthcoming offsprings fatehrs genes use up mothers power to ensure their transmission

Question 42

assisted reproductive technologies

Answer 42

in vitro fertilization intra-cytoplasmic sperm injection ooplasm donation could disrupt the correct maintenance of imprinting, may be associated with imprinting defects