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G and H > Epigenetic and genetics of Development > Flashcards

Epigenetic and genetics of Development Flashcards

week 11

1
Q

Epigenetics

A

study of changes in phenotype or gene expression caused by mechanisms that do not involve changes in underlying DNA seq

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2
Q

How do embryonic cells become different if they are exact copes of a parent cell?

A

Differentiated cells arise from a sequence of increasingly specialized progenitor cells intermediates via epigenetic changes

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3
Q

How does chromatin change to euchromatin or heterochormatin?

A

epigenome controls the switching between these states.

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4
Q

what two mechanisms induce epigenetic change?

A

Histone modification

DNA methylation

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5
Q

How does Histone modification act as a mechanism for epigenetic change?

A

Sets a genes expression state (modifies activity of DNA wrapped around them)

Increased methylation of histone tail = repressed gene expression (promotes heterochromatin formation)

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6
Q

What is DNA methylation?

A

Covalent addition of a Me group at C5 of cytosine ( = 5-methylcytosine=5MEC)

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7
Q

What is a CpG island and how does it affect gene expression?

A

region of DNA containing high freq of CpG sites

methylation around gene promoters silence gene expression

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8
Q

How does DNA methylation repress transcription?

A

directly interferes with transcription factor binding, indirectly attracts specific repressor proteins.

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9
Q

Epigenetic Reprograming

A

Time during early embryonic development where all epigenetic tags are erased and remodelled.

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10
Q

Steps of epigenetic reprogramming

A

Parental epigenetic tags erased in formation of germ cells

Aprox 100 genes are reset. Their expression of allele depends on parent of origin.

Fertilization

Erasure of epigenetic tags so that all genes are available for embryonic development

As cell becomes more specialized, methylation increases.

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11
Q

What are imprinted genes?

A

genes that show expression of only maternal OR paternal allele

one copy is epigenetically silenced

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12
Q

is imprinting transmitted?

A

yes

Mitosis: epigenetic modifications are reproduced in new strands

Meiosis: imprints are removed and reset such that sperm is rewritten with paternak arks and oocytes rewritten with maternal marks.

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13
Q

Epigenetic traits vs trait caused by DNA mutation

A

Epigenetic traits DONT change the nucleotide seq but DO affect how genes behave.

Epigenetic trait = stable phenotype from change involving chemical modification of DNA bases or histone proteins

Mutations = change in DNA sequence

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14
Q

influence of diet in epigenome

A

Nutrient folic acid, VB and SAM-e are key components of methyl-making pathway

Diet high in these nutrient rapidly alter gene expression, especially during early development

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15
Q

intergenerational: transmission of epigenetic marks from one generation to another

Transgenerational: germ-line mediated inheritance of epigenetic information between generations in the absence of continued direct environmental influence. (not directly exposed).

A

Intergenerational: transmission of epigenetic marks from one generation to another

Transgenerational: germ-line mediated inheritance of epigenetic information between generations in the absence of continued direct environmental influence. (not directly exposed).

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16
Q

What ages are males and females sensitive to environmental exposure that leads to a transgenerational response?

A

Males: around age 10 when puberty begins with the production of sperm

Females:  while still in the womb as eggs are being formed
17
Q

what is the function of HOX genes?

A

Genes that direct formation of many body structures during early embryonic development

Controlled expression of a unique combination of homeobox genes = formation of each body segment

18
Q

What is a complication of mutation in a HOX gene?

A

syndactyl

19
Q

How is sex genetically determined?

A

SRY gene = transcription factor

SRY encodes TDF (Transcription factor protein)

TDF = HMG box that binds to DNA = initiates male sex determination and regulates male development.

20
Q

What are regions of homology on each arm of the X and Y chromosome called?

A

pseudoautosomal regions (bind in meiosis)

21
Q

How are XX males and XY females possible?

A

SRY is near telomere and PAR

Telomere region is prone to damage

Incorrect repair of this region = SRY being lost to X via crossing over

22
Q

PAX6

A

Master control gene of ocular and neural tube development

11p13

23
Q

What is Aniridia and what gene does it impact?

A

development of the eye but without an iris (aniridia) → cannot control light entering the eye

Pax6 gene 11p13

24
Q

What is a critical period?

A

Time when organs are developing = emryois are most vulnerable to toxins, viruses and genetic abnormalities (due to elevated cell division during organogenesis)

25
Q

Tetratogens

A

Agents that disrupt normal cellular development during embryogenesis = malformations and birth defects

26
Q

3 categories of tetraogens

A

Drugs

Nutrients

Infection

27
Q

What condition can arise from exposure to thalidomide

A

Phocomelia (seal limb) = total absence of long bones in limb

The difference in phenotype due to how early in the critical period of mother started it, for low long and dose

28
Q

Describe the cause of willi prader syndrome

A

loss of paternal 15q11-13 region so only MATERNAl is remains, however these are switched off = disease

29
Q

describe the cause of angleman disease

A

loss of maternal genes so only PATERNAL genes remains, however, these are switched off = disease

30
Q

clincial features of willi prader syndrome

A
  • chronic feeling of hunger → hyperphagia
  • life-threatening obesity
31
Q

compare Angleman And WP syndrome

A

both =methylation defect

AM= paternal uniprental disomy
WP = maternal uniparental disomy

32
Q

epigenome

A

all chemical compounds that have been added to entire DNA as a way to regulate genes

33
Q

methylome

A

set of nucleic acid methylation modification in genome or particular cell

34
Q

Phocomelia clinical features

A

affects upper and lower limbs
-bones of affected limb missing/unaffected
-limb extremely short
-severe = hand/foot attaches to trunk

35
Q

haploinsufficiency

A

only a single functional copy of a gene does not produce enough [product to produce wild-type = abnormal or disease state

36
Q

What is the affect of histone acetylase on chromatin structure and gene trabscription

A

histone acetylase = increased histone acetylation = acetyl group is added = decreases the binding between histones and DNA = open structure (euchromatin)

G and H (16 decks)

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