Chromatin’s rolein eukaryotic gene regulation

Question 1

Genomic imprinting

Answer 1

Certain genes are expressed in a parent-of-origin-specific manner.

It is an inheritance process independent of the classical Mendelian inheritance.

Imprinted genes are either expressed only from the allele inherited from
- the mother (eg. H19 or CDKN1C).
- or from the allele inherited from the father (eg. IGF-2).

Question 2

CpG islands

Answer 2

CpG islands are DNA methylations regions in promoters known to regulate gene expression through transcriptional silencing of the corresponding gene.

Question 3

Prader-Willi syndrome

Answer 3

A genetic disorder that affects many parts of the body and their growth. It causes mental and behavioral problems.

Condition Highlight
- Urgent medical attention is usually recommended by healthcare providers

Can be dangerous or life threatening if untreated

How common is condition?
- Extremely rare (Fewer than 1,000 cases per year in US)

Is condition treatable?
- Treatable by a medical professional

Does diagnosis require lab test or imaging?
- Often requires lab test or imaging

Time taken for recovery
- Can last several years or be lifelong

Question 4

Prader-Willi syndrome: Pedigree Pattern

Answer 4

The syndrome can caused by mutation of the paternally derived SNRPN allele and imprinting of the maternally derived SNRPN allele

Question 5

Prader-Willi syndrome: Consanguineous mating

Answer 5

Rare recessive phenotype

Question 6

Prader-Willi syndrome: Transmission of a recessive PWS allele

Question 7

Genomic imprinting} more

Answer 7

Theepigeneticphenomenon by which certaingenesareexpressedin a parent-of-origin-specific manner.
— Whole chromosomes: Dosage compensations
— Angelman Syndrome
— Prader-Willi Syndrome

If thealleleinherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed.

If the allele from the mother is imprinted, then only the allele from the father is expressed.

Forms of genomic imprinting have been demonstrated in fungi, plants and animals.

Genomic imprinting is a fairly rare phenomenon in mammals; most genes are not imprinted. (Wiki)

Question 8

Developmental verbal dyspraxia (verbal dyspraxia / apraxia of speech)

Answer 8

is a neurological motor disorder that impacts upon the child’s ability to plan and execute the movement that is required to produce speech.

Cause: mutations in the Human FOX P2 Gene.

Frequently associated with Uniparental disomy.
(UPD).

Question 9

Disomy:

Answer 9

The condition of having a chromosome represented twice in a chromosomal complement.

Question 10

Uniparental Disomy(UPD)

Answer 10

A person receives two copies of achromosome, or part of a chromosome, from one parent and no copies from the other parent

Two types

-heterodisomy
(meiosis I error)

-isodisomy
(meiosis II error)

Potential medical
consequences
-expose recessive alleles
-parental
imprinting problems

Question 11

Human FOX P2 gene

Answer 11

Absence of a Paternally Inherited FOXP2 Gene in Developmental Verbal Dyspraxia

Question 12

Parthenogenesis

Answer 12

A form of asexual reproduction found in females;

Growth and development of embryos occurs without fertilization by a male.

In animals, parthenogenesis means development of an embryo from an unfertilized egg cell.

Question 13

The IGF2 gene

Answer 13

Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin.

In humans, on chromosome 11p15.5,

In mice, at distal chromosome 7.

In both organisms, Igf2 is imprinted, with expression resulting favorably from the paternally inherited allele.

Question 14

Parthenogenesis is not seen in mammals
Hypothesis:

Answer 14

Hypothesis:
Genomic imprinting may play a significant role in suppressing parthenogenesis.

Question 15

Kaguya Mouse

Answer 15

using one egg from an immature parent,
thus reducing maternal imprinting,

– modifying it to express the gene Igf2 (maternally active),
(which is normally only expressed by the paternal copy of the gene).

Even with this, only two of 457 eggs developed to maturity.

Deletion of Cpg islands —> targeted mutagenesis

Question 16

Virgin birth:

Answer 16

Fatherless mouse born from unfertilised egg survives to adulthood and gives birth to healthy litter

Question 17

The Tug-of-war hypothesis

Answer 17

Imprinting has evolved in mammals because of the conflicting interests of maternal and paternal genes in relation to the transfer of nutrients from the mother to her offspring.

Question 18

Mysteries of Epigenetics: There’s More to Genes Than DNA

Answer 18

A normal 4-day-old mouse embryo (L) and an embryo of the same age that has been manipulated to contain maternal chromosomes only (parthenogenote). At this stage, the embryos (blastocysts) appear similar, but the parthenogenote will soon die, underscoring the importance of inheriting imprinted genes from both parents. Different cell types are stained green or red.

Question 19

Epigenetic changes to last for 300 generations

Answer 19

Researchers from UMD found that the same gene for expressing a red fluorescent protein is always expressed (ON), when it is inherited from the mother, but when inherited from the father can lose expression (turn OFF) forever if the mother lacks the gene.

Question 20

Scientists successfully induced a virgin birth in fruit flies by manipulating specific genes