LEC44: Non-Mendelian Inheritance Flashcards Preview

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Flashcards in LEC44: Non-Mendelian Inheritance Deck (40)
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1

epigenetics is?

study of reverisble heritable changes in gene fxn that occur w/o a change in sequence of nuclear DNA 

gene-regulatory info that isn't expressed in DNA sequences but can be trasmitted from 1 generation to the next 

2

are epigenetic changes heritable? 

mitosis or meiosis related?

yes, heritable 

patterns of expression are across cell mitoses, not meiosis 

3

how does epigenetic change occur?

series of structural modifications to the DNA, or to underlying chromatin that packages DNA, that can affect gene expression without changing primary DNA sequence 

through: DNA methylation, genomic imprinting, X-inactivation, environemnt/nutrition and EWAS, IVF

4

what does epigenetics control?

cell development

thus explains tissue-specific patterns of gene expression that're critical for appropriate development to occur despite cells all having same genomic complement 

 

5

what are transcriptional-level molecular mechanisms that mediate epigenetic phenomena?

1) modifications to DNA via methylation at CpG dinucleotides

2) modifications and variations to histones via methylation, acetylation

3) modifying non-coding RNA 

 

6

what is DNA methylation? where usually occur?

methyl group added at at CpG nucleotide islands or gene promotoers 

if added to C of CpG island, forms methylcytosine, the "5th base of DNA"

7

what does methylation of DNA at CpG islands and gene promoters cause? 

what is usual state of CpG islands? 

methylation = represses transcription 

USUALLY, CpGs are methylated (> 80%)

thus gene is usually OFF

8

if a CpG island or gene promoter is unmethylated, what's the state of the gene?

unmethylated = active gene

 

9

what is X-inactivation

females inactivate 1 copy of X in each somatic cell by random process during embryogenesis

gene-dose compensation strategy mammals use to equalize trascript abundance btwn females who have 2 copies of X-linked genes and males who have single copy

10

why does x chromosome inactivation occur?

b/c there's an inequality of gene content between males and females, since females are 46,XX and males are 46,XY

X chrom is large, ~1000 genes, Y is small, ~50 genes

females thus "compensate" by inactivating 1 X chromosome to make a single "dosage" of X-linked genes

11

which X is inactivated and when for X chromosome inactivation?

inactivation occurs randomly in somatic cells during 100-200 cell stage of embryogenesis

12

what is result of X inactivation in offspring?

progeny cells all have same inactivated X chromosome as their ancestor 

this creates mosaic females with some cells having paternal X inactive, other cells have maternal X inactive

13

what does calico cats' fur patterning demonstrate?

all calico cats are female and heterozygous for an X-linked gene that codes for either black or orange fur

2 colors represent skin cells that've inactivated different X chromosomes

X-linked inactivation results in mosaic coloration

14

what is anhidrotic ectodermal dysplasia? what does it show about X linked inactivation?

an X-linked recessive disease caused by mtuations in the EDA gene 

disease severity in females is dependent on proportion of cells that've inactivated the normal EDA copy 

if female has the mutant EDA allele, X with the mutant EDA allele is active some places; X without mutant is active elsewhere; thus have normal skin in some areas and regions without sweat glands in others

this is mosaicism

15

when do X-linked diseases phenotypically manifest?

when cells that have inactivated the wild-type X 

explains why X-linked diseases more commonly manifest in males than females

16

how does X-linked inheritance occur?

cannot be male-to-male transmission 

female carriers are affected if X-chromosome carrying normal allele is inactive in nearly all cells

17

genomic imprinting?

epigenetic phenomenon where expression status of a gene is dependent on its parental origin 

18

when does imprinting occur?

generated in germline cells so chromosomal regions are marked as being maternally or paternally derived and differentially expressed in fertilized zygote

19

what kind of expression do non-imprinted genes show?

bi-allelic expression 

 

20

what kind of expression do imprinted genes exhibit?

mono-allelic expression & epigenetic marks 

 

21

if the same mutation (i.e. deletion) on the maternal and paternal chromosome causes different phenotypes in offspring, what does this suggest?

confirms the presence of imprinted gene(s) influencing phenotype within the mutation (deletion) region 

 

22

what are "imprinted domains"? what do they exhibit?

clusters of imprinted genes 

~80% of imprinted genes occur in clusters 

 

23

how many imprinted genes do we know?

~80 in humans, >100 in mouse 

there are many unidentified imprinted human genes

24

what genes are imprinted in cancer/BWW syndrome? 

in prader-willi/angelman syndrome?

IGF2 and IGF2R - growth regulators - BWW/cancer 

UBE3A and MAGEL2 - brain development - PW/angelman

25

what causes both prader-willi and angelman syndrome?

what is difference between them?

both: inheritance of deletion of proximal chr15, causing absence of genes expressed from maternal or paternal allels, causing disease b/c of functional nullisomy

ANGELMAN: MATERNAL deletion 

P-W: PATERNAL deletion

26

what is the locus effected in P-W/angelman syndromes?

imprinted genes in 15q11-q13

occurs b/c some genes are only expressed from paternally-derived allele, some from maternal; thus where deletion occurs determines if you get prader willi (PATERNAL deletion) or Angelman (MATERNAL deletion)

27

what are the possible molecular causes of Prader-Willi syndrome?

15q13 locus mutations: 

65-75%: paternal deletion 

20-30%: maternal uniparental disomy 

2-5%: imprinting defects

 

28

what are the possible molecular causes of Angelman syndrome?

all result in loss of the maternally-expressed imprinted gene UBE3A

65-75%: maternal deletion 

3-7%: paternal uniparental disomy (UPD) 

5-11%: UBE3A mutation 

3%: imprinting defects

 

29

parental conflict hypothesis?

hypothesis: inequality btwn parental genomes due to imprinting is a result of differing interests of each parent in terms of evolutionary fitness

PATERNAL genes: promote offspring growth, at expense of mother 

MATERNAL genes: limit growth, to conserve resources for survival, to produce more offspring

30

what is relationship between imprinted genes and environmental influences?

environmental cues thought play a role in gene expression patterns via imprinted regions of genes

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