Today: Genomic Imprinting and Epigenetics

haploid diploid X 23 in humans X 23 in humans X 23 in 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: Lamarck was right? Sort of… Image from:

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 a B* a B* A* b A* 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*a bB* A*a bB* a B* a B* A* b A* 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*a bB* A*a bB* A*a bB Aa bB* a B* a B* A* b A* 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*a bB* A*a bB* A*a bB Aa bB* A*b, A*B, ab, aB Ab, AB*, ab, aB* a B* a B* A* b A* 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 7.11 Changes in methylation during gamete development alter the imprint

To date, imprinting has been identified in dozens of mammalian genes 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 7.12 The deletion is the same in males and females, but the expression is different depending on who you received the normal version from.