4.

14 Genomic (Parental) Imprinting and Gene Silencing

• Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed in a parent-of-

origin-specific manner
• It can occur as a random event during the formation of egg or sperm cells and early fetal
development. In germline cells the imprint is erased and then re-established according to the sex of the
individual, i.e. in the developing sperm (during spermatogenesis), a paternal imprint is established,
whereas in developing oocytes (oogenesis), a maternal imprint is established
• Genes or regions of a chromosome are imprinted on one homolog but not the other
Normal Igf2 allele
is expressed.
Paternal
chromosome
Maternal
chromosome Normal-sized mouse
Normal Igf2 allele (wild type)
is not expressed.
(a) Homozygote

Mutant Igf2 allele Mutant Igf2 allele

inherited from mother inherited from father

Normal-sized mouse (wild type) Dwarf mouse (mutant)

Normal Igf2 allele Mutant Igf2 allele
is expressed. is expressed.

Mutant Igf2 allele Normal Igf2 allele

is not expressed. is not expressed.
(b) Heterozygotes
 Prader-Willi and Angelman syndromes

• The involved region of chromosome 15 is imprinted differently in male and female gametes ..
This is not usual in the genome as for most genes both copies work!
• Prader-Willi syndrome (PWS) is due to a deletion in the long arm of chromosome 15 (15q1)
which comes from the father, and the mother’s chromosome has no deletion. This leads to the
loss of genes including SNRPN. Normally, the paternal gene is expressed while
the maternal gene is silenced - https://www.youtube.com/watch?v=8CKN6idlE80
• If the maternal segment is deleted and an undeleted paternal chromosome remains, an entirely
different disorder, Angelman syndrome (AS) occurs due to loss of other genes including UBE3A.
Normally, the maternal gene is expressed while the paternal gene is silenced

Uniparental disomy
 4.15 Extranuclear Inheritance Modifies Mendelian Patterns

• Extranuclear inheritance involves genes not found in the nucleus but rather in cytoplasmic
organelles
• An organism’s phenotype can be affected by genes contained in the DNA of mitochondria
and chloroplasts (organelle heredity)
• Following fertilization, the developing zygote’s phenotype is determined not by the
individual’s genotype but by gene products directed by the mother’s genotype

• A cell’s energy supply is largely dependent on aerobic cellular respiration, and disruption
of any mitochondrial gene by mutation may potentially have a severe effect on that
organism

• Mitochondrial DNA (mtDNA) is vulnerable to mutations since the repair mechanism is

not very effective and free radicals from cellular respiration increase the mutation rate

• Myoclonic epilepsy and ragged-red fiber disease (MERRF) is a mitochondrial human

disorder wherein only the offspring of affected mothers inherit the disorder while
offspring of affected fathers are normal. Symptoms include ataxia (lack of muscular
coordination), deafness, dementia, and epileptic seizures; muscle fibers appear red and
ragged