Genetic imprinting

Question 1

Genetic imprinting

Answer 1

Monoallelic expression of autosomal genes depending on the sex of transmitting parent.

Question 2

How does a gene get silenced in genetic imprinting?

Answer 2

epigenetic modification such as DNA methylation

or any other changes in proteins that bind to DNA (cytosine methylation and histone modifications.)

Question 3

androgenetic

Answer 3

Fertilized egg (zygote) with all paternal chromosomes

Question 4

gynogenetic

Answer 4

Fertilized egg (zygote) with all maternal chromosomes

Question 5

Why do androgenetic and gynogenetic embryos fail to complete development?

Answer 5

because of imprinted genes, which are expressed differently during development depending on their parental origin. Even though they are autosomal and present in two copies, one maternal and one paternal, only one of the two alleles is expressed.

Question 6

Are the same paternal imprint kept on the offsrpting and passed down?

Answer 6

no, imprints are erased and reapplied in the germline so that only maternal imprints are seen in oocytes and only paternal imprints are seen in sperm

Question 7

Disorders caused by disruption of imprinted genes

Answer 7

Prader-Willi

Angelman

Question 8

How do gynogenones develop?

Answer 8

They have poorly developed extraembryonic tissues, differentiated fetal tissues (Like ovarian teratoma)

Question 9

How do Androgenones develop?

Answer 9

They have poorly developed embryonic tissue but extensive extraembryonic tissue (hydatidiform mole

Question 10

Examples of imprinted genes

Answer 10

Examples include IGF2, IGF2R, H19, Insulin, Some G proteins

Question 11

How are imprinted genes positioned on the DNA

Answer 11

Imprinted genes oftentimes cluster but different genes within the same cluster may be imprinted in opposite direction (Mat vs Pat)

Question 12

Prader-Willi

Answer 12

Cause: deletion (5-6 Megabases) at 15q11-q13 (paternal allele deleted)
Symptoms: 
Initial feeding problems
Later hyperphagia
Obesity
Short stature
Small hands and feet
Mild-moderate MR
Hypogonadism

Question 13

Angelman

Answer 13

Cause: deletion (5-6 Megabases) at 15q11-q13 (maternal allele deleted)
symptoms: Ataxic gait (unsteady walking)
Absent speech
Prominent jaw
Inappropriate laughter
Moderate-severe MR ( mental retardation)

Question 14

What can cause imprinting disorders?

Answer 14

Deletion
point mutation
Unnniparental disomy (innheritance of two copies from one parents -> caused by trisomy rescue)

Question 15

Beckwith Wiedemann syndrome

Answer 15

Cause:
Mutations in one of 11p15.5 alleles

(IGF2 is a fetal growth factor and is paternally expressed
H19 is an untranslated RNA that is maternally expressed
Only one of the 2 genes can be expressed at any given time from the same chromosome)

Clinical phenotype: 
overgrowth
Large for gestational age
Macroglossia
Nephromegaly and adrenomegaly
Omphalocoele
Some predisposition to kidney/liver/adrenal tumors

Question 16

Waht are histones?

Answer 16

Histones are globular proteins with a flexible N terminus tail that bind to DNA to form nucleosomes

Question 17

How are histone modification implemented?

Answer 17

acetylation of specific lysine residues by histone acetyltransferases and deacetylation by histone deacetylase

The methylation of lysine and arginine residues by histone methytransferases and the demethylation of lysine residues by histone demethylases

Question 18

What kind of DNA configureation does trimethylation cause?

Answer 18

Generally, tri-methylation at H3-K4, H3-K36, or H3-K79 results in an open chromatin configuration and is therefore characteristic of euchromatin.

Question 19

What are some types of histone modification?

Answer 19

Methylation
Acetylation
phosphorylation of specific serine groups by histone kinases
attachment of ubiquitin, small ubiquitin-like modifiers, and poly ADP-ribose (PAR) units

Question 20

How do you read H3K27me3?

Answer 20

histone 3
aminno acid lysine, 27th position from the N terminus
trimethylation

Question 21

What type of disease does mutation in many of the histone modification and chromatin configuration genes result in?

Answer 21

ntellectual disability syndromes such as Weaver syndrome, Sotos syndrome, Kabuki syndrome