Today: Genomic Imprinting and EpigeneticsToday: Genomic Imprinting and Epigenetics

haploid

diploid

X 23in humans X 23

in humans

X 23in humans

Inheritance = The interaction between genes inherited from Mom and Dad.

Sex-linked traits: Genes on the X chromosome

No one affected, female carriers

50% of males affected, 0 % female affected

50% males affected, 50% females affected

A= normal ; a= colorblind

similar to Fig 4.13

Human sex chromosomes

(includes Mic2 gene)

Fig 4.14

males and females may have different numbers of chromosomes

Fig 3.18

Tbl 7.1

dosage compensation

At an early stage of embryonic development

The epithelial cells derived from this

embryonic cell will produce a patch of

white fur

While those from this will produce a patch of black fur

Fig 7.4

Promotes compaction

Prevents compaction

Mammalian X-inactivation involves the interaction of 2 overlapping genes.

The Barr body is replicated and both

copies remain compacted

Barr body compaction is heritable within an individual

• 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

Epigenetics: http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html

Lamarck was right? Sort of…

Image from: http://www.sparknotes.com/biology/evolution/lamarck/section2.rhtml

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-inherited or the paternally-inherited allele **Not both

Genomic Imprinting:Methylation of genes during gamete production.

A hypothetical example of imprinting

A=curly hair

a=straight hair

B=beady eyes

b=normal

*=methylation

A* in males

B* in females

aB*

aB* A*

bA*b

A hypothetical example of imprinting

A=curly hair

a=straight hair

B=beady eyes

b=normal

*=methylation

A* in males

B* in females

A*abB*

A*abB*

aB*

aB* A*

bA*b

A hypothetical example of imprinting

A=curly hair

a=straight hair

B=beady eyes

b=normal

*=methylation

A* in males

B* in females

A*abB*

A*abB*

A*abB

AabB*

aB*

aB* A*

bA*b

A hypothetical example of imprinting

A=curly hair

a=straight hair

B=beady eyes

b=normal

*=methylation

A* in males

B* in females

A*abB*

A*abB*

A*abB

AabB*

A*b, A*B,ab, aB

Ab, AB*,ab, aB*

aB*

aB* A*

bA*b

similar to Fig 7.10

Thus genomic imprinting is permanent in the somatic cells of an animal

–However, the marking of alleles can be altered from generation to generation

• 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

Imprinting and DNA Methylation

• For most genes, methylation results in inhibition of gene expression

–However, this is not always the case

Haploid female gametes transmit an unmethylated gene Haploid male gametes transmit

a methylated gene

Fig 7.11Changes in methylation during gamete development alter the imprint

To date, imprinting has been identified in dozens of mammalian genes Tbl 7.2

Tbl 7.2

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

• 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)

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