Epigenetics, Imprinting, and Uniparental Disomy

Question 1

epigenetics

Answer 1

the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence

Question 2

pronuclear transplantation

Answer 2

androgenetic - combining male nuclei with another male nuclei, leads to good membranes and placenta by hydatidiform moles

gynogenetic - two female nuclei, good embryo, poor membranes and placenta, forms teratomas

Question 3

genomic imprinting

Answer 3

the differential expression of allels determined by the sex of the parent from whome each allele was inherited

Question 4

mechanisms involved in imprinting

Answer 4

methylation/demethylation of cytosines

acetylation/de-acetylation of histones

methylation/de-methylation of histones

interference RNAs

Question 5

Symptoms of Prader-Willi Syndrome

Answer 5

hypotonia and failure to thrive in infancy

obesity and hyperphagia

characteristic facies

small hands and feet

hypogonadism

Question 6

Cause of Prader-Willi Syndrome

Answer 6

70% of cases due to deletion of 15q11, always the paternal chromosome 15

can also be uniparental heterodisomy or isodisomy

Question 7

Symptoms of Angelman Syndrome

Answer 7

postnatal growth deficiency

severe mental retardation

paroxysms of inappropriate laughter

ataxia and jerky arm movements

seizures

Question 8

Cause of Angelman Syndrome

Answer 8

deletion of 15q11-13 in 70% of cases

chromosome with deletion is always the matrnal chromosome 15

point mutations UBEA3A in about 10% of cases

Question 9

PWS-Angelman Region of 15q11-13

Answer 9

depending on which genes are activated or repressed in this region, different diseases can arise when there are deletions

Question 10

Symptoms of Beckwith-Wiedemann Syndrome

Answer 10

macrosomia, macroglossia, visceromegaly, omphalocele, renal abnormalities, ear creases, neonatal hypoglyciemia, tumors

Question 11

Causes of Beckwith-Wiedemann Syndrome

Answer 11

mutations of imprinting centers 1 or 2, paternal uniparental disomy

many other mechanisms, but the end result is altered imprinting

Question 12

determinants of epigenetic variation

Answer 12

nutrition, smoking, environmental exposures, alcohol, medications, early experiences based on parental behavior

Question 13

Dutch Hunger Winter of 1944-1945 and epigenetics

Answer 13

famine around the time of conception caused reduced IGF2 methylation

60 years later the altered levels of methylation persisted, and these individuals developed insulin resistance

children of these individuals were also smaller than expected

Question 14

bariatric surgery and epigenetic effects

Answer 14

children born after dramatic maternal weight loss are less prone to obesity compared with their siblings born before surgery

increased maternal weight gain between two pregnancies is associated with increased body weight in the second child

Question 15

Overkalix Study

Answer 15

situated in isolated community in Sweden

studied the effects of food shortage and abundance on the slow growth period before puberty

found that shortage food during father’s SGP protected child from CV disease mortality, and shortage during grandfather’s SGP protected child from diabetes

abundance of food during grandfather’s SGP associated with increased diabetes related mortality

Question 16

pesticide exposure and epigenetics

Answer 16

mice exposed to vinclozolin early ingestation results in offspring with impaired spermatogenesis

impairment in spermatogenesis persists in multiple subsequent generations

Question 17

licking, grooming, and epigenetics

Answer 17

study showed that offspring mother mice that lick and groom tend to have more demethylation of Nr3c1, increased serotonin, increaced NGF1-A expression, and increased glucocorticoid receptor expression in hippocampus

this led the mice themselves to have more hippocampal glucocorticoid receptor and have lower glucocorticoid levels in response to stress

addition of methionine that promotes methylation caused these mice to behave like mothers who do not groom and lick offspring

Question 18

acquired diseases affected by epigenetic changes

Answer 18

asthma, allergy, obesity, diabetes, cancer, fetal alcohol effects, autism spectrum disorder