Imprinting disorders

Effect depends on whether maternal or paternal chromosome is affected.

Specific counselling

Imprinting effects -

example of parental sex-

dependent influence on

phenotype

• mare x donkey =mule,
• stallion x donkey = hinny (shorter

ears, a thicker mane and tail, and
stronger legs than the mule)

Imprinting - the differential expression of alleles depending on the parent of
origin

An imprinting defect is an abnormality of the parent-of-origin-specific gene
regulation, such that a maternal allele or genomic domain has the resulting
pattern of gene expression) of a paternal allele or genomic domain, or vice versa.

Imprinted genes are often differentially methylated!

EPIGENETICS..

Genetic imprinting - principles of

inheritance

Idealized pedigrees for maternal and paternal imprinting. These figures are meant to diagram
what a pedigree of human disease that had imprinting effects might look like. The term
"imprinting" implies a modification in expression of a gene or allele. An "imprintable" allele will be
transmitted in a Mendelian manner, but expression will be determined by the sex of the
transmitting parent. In these idealized pedigrees the term "maternal imprinting" is used to imply
that there will be no phenotypic expression of the abnormal allele when transmitted from the
mother, and paternal imprinting is used to imply that there will be no phenotypic expression when
transmitted from the father. Because there will be a phenotypic effect only when the gene in
question or chromosome segment in question is transmitted from one or the other parent, there
are a number of nonmanifesting carriers.

link

Paternal imprinting

Maternal imprinting

Pathway for the

Methylation of Cytosine in

the Human Genome

A family of three active enzymes, the DNA

methyltransferases (DNMTs), catalyzes the methylation

of the 5 position of the cytosine ring, using S-adenosyl-

methionine as the donor molecule for the methyl group

(CH3).

Methylation is imposed only on cytosines that precede a

guanosine in the DNA sequence (the CpG dinucleotide).

NEJM 349:2042

DNA (CG) methylation

A methylating
enzyme
(white) binds
to its target
site (red) on
DNA;

the

methyl donor
is shown in
green

Distribution of CpG Dinucleotide and

Differences in Methylation Patterns between

promoters and the rest of DNA

NEJM 349:2042

Life cycle of methylation

imprints

IC -Imprinting control element. Grey indicates modification and

white indicates no modification at the corresponding alleles.

Parental chromosomes are marked according to their sex in blue

(male) or red (female). The reading (transcriptional interpretation

of the primary imprints) in the developing embryo is indicated by

arrows.

Nature Rev Gen

Prader-Willi

Syndrome:

phenotype

Am J Med Gen

http://health.allrefer.com/

75% of the patients have large

chromosomal deletions of +/- 4

Mb of 15q11-13 region, Always,

the deletion is on the

paternally inherited

chromosome.

sou

Angelman Syndrome

• Developmental delay,

functionally severe

• Speech impairment, none or

minimal use of words;

receptive and non-verbal

communication skills higher

than verbal ones

• Movement or balance

disorder, usually ataxia of

gait and/or tremulous

movement of limbs

• Behavioral uniqueness: any

combination of frequent

laughter/smiling; apparent

happy demeanor; easily

excitable personality, often

with hand flapping

movements; hypermotoric

behavior; short attention

span

• „HAPPY PUPPET”

appearance

http://www.asclepius.com/

70% of the patients have

deletions of +/- 4 Mb in the

15q11-13 region. The deletion is

always on the maternally

inherited chromosome.

Causes for

Prader-Willi

Syndrome (PWS) and Angelman

Syndrome (AS)

Red -maternall chrmosome genes,

Blue- paternall chromosome

Ann Rev 2001

No single gene muations.
A polygenic defect?

Imprinting -

podsumowanie

• Forma monoallelicznej ekspresji genu, w

której wyciszeniu ulega kopia od rodzica
zawsze tej samej płci

• Niespójna nomenklatura
• Niejasne pochodzenie ewolucyjne – być

może związane z antagonizmem
płód(ojciec)-matka

• Inaktywacja często (zawsze?) związana z

metylacją DNA