Today: Genomic Imprinting and Epigenetics

1
Today Genomic Imprinting and Epigenetics
2
haploid
X 23 in humans
X 23 in humans
diploid
X 23 in humans
Inheritance The interaction between genes
inherited from Mom and Dad.
3
Sex-linked traits Genes on the X chromosome
A normal a colorblind
No one affected, female carriers
50 of males affected, 0 female affected
50 males affected, 50 females affected
similar to Fig 4.13
4
Human sex chromosomes
Fig 4.14
(includes Mic2 gene)
5
Fig 3.18
males and females may have different numbers of
chromosomes
6
Tbl 7.1
dosage compensation
7
Fig 7.4
The epithelial cells derived from this embryonic
cell will produce a patch of white fur
At an early stage of embryonic development
While those from this will produce a patch of
black fur
8
Mammalian X-inactivation involves the interaction
of 2 overlapping genes.
Promotes compaction
Prevents compaction
9
(No Transcript)
10

• A few genes on the inactivated X chromosome are
  expressed in the somatic cells of adult female
  mammals
• Pseudoautosomal genes(Dosage compensation in
  this case is unnecessary because these genes are
  located both on the X and Y)
• Up to a 25 of X genes in humans may escape full
  inactivation
• The mechanism is not understood

11
Lamarck was right? Sort of
Epigenetics http//www.pbs.org/wgbh/nova/science
now/3411/02.html
Image from http//www.sparknotes.com/biology/evol
ution/lamarck/section2.rhtml
12
Genomic Imprinting

• Genomic imprinting is a phenomenon in which
  expression of a gene depends on whether it is
  inherited from the male or the female parent
• Imprinted genes follow a non-Mendelian pattern of
  inheritance
• Depending on how the genes are marked, the
  offspring expresses either the maternally-inherite
  d or the paternally-inherited allele Not both

13
Genomic Imprinting Methylation of genes during
gamete production.
14
A hypothetical example of imprinting
a B
a B
A b
Acurly hair astraight hair Bbeady
eyes bnormal methylation A in males B in
females
A b
15
A hypothetical example of imprinting
a B
a B
A b
Acurly hair astraight hair Bbeady
eyes bnormal methylation A in males B in
females
A b
Aa bB
Aa bB
16
A hypothetical example of imprinting
a B
a B
A b
Acurly hair astraight hair Bbeady
eyes bnormal methylation A in males B in
females
A b
Aa bB
Aa bB
Aa bB
Aa bB
17
A hypothetical example of imprinting
similar to Fig 7.10
a B
a B
A b
Acurly hair astraight hair Bbeady
eyes bnormal methylation A in males B in
females
A b
Aa bB
Aa bB
Aa bB
Aa bB
Ab, AB, ab, aB
Ab, AB, ab, aB
18

• Thus genomic imprinting is permanent in the
  somatic cells of an animal
• However, the marking of alleles can be altered
  from generation to generation

19
Imprinting and DNA Methylation

• Genomic imprinting must involve a marking process
• At the molecular level, the imprinting is known
  to involve differentially methylated regions
• They are methylated either in the oocyte or sperm
• Not both

20

• For most genes, methylation results in inhibition
  of gene expression
• However, this is not always the case

21
Fig 7.11
Changes in methylation during gamete development
alter the imprint
Haploid female gametes transmit an unmethylated
gene
Haploid male gametes transmit a methylated gene
22

• To date, imprinting has been identified in dozens
  of mammalian genes

Tbl 7.2
23
Tbl 7.2
24

• Imprinting plays a role in the inheritance of
  some human diseases Prader-Willi syndrome (PWS)
  and Angelman syndrome (AS)
• PWS is characterized by reduced motor function,
  obesity, mental deficiencies
• AS is characterized by hyperactivity, unusual
  seizures, repetitive muscle movements, mental
  deficiencies
• Usually, PWS and AS involve a small deletion in
  chromosome 15
• If it is inherited from the mother, it leads to
  AS
• If it is inherited from the father, it leads to
  PWS

25

• AS results from the lack of expression of UBE3A
  (encodes a protein called EA-6P that transfers
  small ubiquitin molecules to certain proteins to
  target their degradation)
• The gene is paternally imprinted (silenced)
• PWS results (most likely) from the lack of
  expression of SNRNP (encodes a small nuclear
  ribonucleoprotein that controls gene splicing
  necessary for the synthesis of critical proteins
  in the brain)
• The gene is maternally imprinted (silenced)

26
Fig 7.12
The deletion is the same in males and females,
but the expression is different depending on who
you received the normal version from.