Genomic imprinting ;

1. Nandana.S
M.Sc.Genetics & Plant Breeding

2.  Genomic Imprinting
 Genomic Imprinting & Mendelism
 Theories of Genomic Imprinting
 Epigenetics
 Mechanism of Genomic Imprinting
 Imprinting Control Regions
 Diseases

3.  The term was coined by Helen Crouse (1960) in the cotext of the
unique inheritance of sex chromosomes in the dipteran insect
Sciara coprophila .
 Genomic imprinting is the process by which only one copy of a
gene in an individual ( either from their mother or father ) is
expressed , while the other is suppressed.
 A gene that exhibits genomic imprinting in both mice and human
is Igf2,which encodes a protein called insulin like growth factor .
 The offsprig inherit one Igf2 allele from their mother and one
from their mother.
 The paternal copy is active but the maternal copy is silent.

4.  Both male and female offspring possess Igf2 genes ; the key
to whether the gene is expressed is the sex of the parent
transmitting the gene.
 It is expressed ony when it is transmitted by a male parent.
 When the paternal copy of Igf2 is deleted in mice ,a small
placenta and low birth weight of offspring results.

5.  A basic tenet of Mendelian genetics is that the parental origin of a gene
doesn’t affect its expression and therefore reciprocal crosses give identical
results .
 Genomic imprinting is an example where Mendel’s laws are not obeyed .
 However maternal and paternal genes are not functionlly equivalent ; a
number of genes have modifications specific to parent of origin and are
said to be imprinted.

6. CONFLIT THEORY
 Haig and westoby [1989] proposed that parent specific gene
expression has evolved because genes of maternal and
paternal origin have conflicting interest with respect to how
much mothers should invest in offspring.
 It predict that paternal genes attempt to acquire more maternal
resources than maternal genes

7.  Genomic imprinting is one form of a phenomenon known as
epigenetics.
 Epigenetics is the field of study focussed on changes in DNA
that do not involve alterations to the underlying sequence.
Example ; DNA methylation

8. Methylation
 DNA methylation is a biological processs by which methyl groups are added
to DNA molecules .
 Methylation can change the activity of a DNA segment without changing the
sequence.
 The pattern of methylation of germ cells is established in each sex during
gametogenesis .
 First the existing pattern is erased by a genomewide demethylation and
then the pattern specific for each sex is imposed during meiosis.
 DNA methylation is successfully established through the activities of
specific enzymes ,DNA methyltransferases ( DNMTs) ,which are capable of
adding methyl groups to the fifth carbon atom of cytosine residues.

9.  Histone proteins and the modifications applied to them are
highly conserved and comprise the most pervasive elements of
imprinting.
 Histone acetylation generally creates an accessible chromatin
conformation while histone deacytelation often coupled to
histone methylation initiates a compressed chromatin
conformation that promotes silencing and the formation of
heterochromatin.

10.  A chromosomal region that acts in a methylation sensitive way , to
determine whether imprinted genes are expressed or not according to the
parent from which the gene derived .
 It regulates the allele–specific activity of imprinted genes in the cluster. ICRs
usually carry a germline derived methylation imprint.
 They have a relatively high level of CpG dinucleotides and have simple
sequence repeats.
 Also called Differently Methylated Region (DMR) and Differently
Methylated Domain. ( DMD).

11.  Beckwith – Wiedemann Syndrome
BWS is a human genomic imprinting disorder that
presents with a wide spectrum of clinical features
incluing overgrowth ,abdominal wall
defects,macroglossia, neonatal hypoglycemia and
predisposition to embyonal tumors.
It is caused by maternally inherited mutation due to
loss of imprinting and regulation at specific site on
chromosome 11.

12.  Angelman syndrome is a disorder of the nervous system
characterised by developmental disabilities.,seizures, speech
deficits and motor oddities.
 The disease is named after English physician Harry
Angelman , who in 1965 happened to see 3 children who
shared a curiously similar constellation of symptoms.
 It occurs when the UBE3A gene is not working properly or is
missing entirely.
 The paternal copy of the gene is imprinted ,or silenced
meaning that only the copy inherited from the person’s mother
is active.
 It occurs due to deletion of maternal chromosome 15 .

14.  The region of chromosome 15 that is involved in Angelman
syndrome also contains another important gene that is imprinted
the other way.
 It occurs when the paternal contribution is lost.
 The patient suffer from extreme feeding problems including
hyperphagia.
 Affected children are also developmentally delayed for motor
skills due to decreased muscle tone .

15.  Tigers and lions don’t normally mate in nature but they can be
done so to produce hybrid offspring.
 The offspring look different depending on who the mother is.
 Paternal imprinting favours the production of larger
offspring and maternal imprinting favours smaller offspring .

16.  A male lion and a female tiger produce a liger –the
biggest of big cat.
 A male tiger and a female lion produce a tigon –a cat that
is about same size as its parents.
 The difference in size and appearance between ligers and
tigon is due to parents differently imprinted genes .