Imprinting

Question 1

what is the mechanism of imprinting?

Answer 1

covalent modification of DNA

either cytosine –> 5-methylcytosine OR
histone modification

Question 2

How is imprinting important for fetal development?

Answer 2

the paternal genome is important for extraembryonic development

the maternal genome is important for fetal development

Question 3

what are the two types of hydatidiform moles?

Answer 3

complete - no fetus or placenta

partial - remnants of placenta and atrophic fetus

Question 4

what is the genotype of a complete mole?

Answer 4

46,XX

uniparental disomy

Question 5

how does a paternally derived mole get all chromosomes from dad?

Answer 5

endoduplication - haploid sperm fertilizes empty ovum and duplicates its chromosomes
dispermy - two sperm fertilize one egg

Question 6

what is the consequence of paternally derived hydatidiform mole?

Answer 6

trophoblast hyperplasia with absent/disorganized fetus

Question 7

what is the genotype of a partial hydatidiform mole?

Answer 7

69,XXY or 69,XXX

Question 8

what is the consequence of paternally derived partial hydatidiform mole?

Answer 8

abundant trophoblast development, poor embryo development

Question 9

what is the consequence of maternally derived hydatidiform mole?

Answer 9

small fibrotic placenta, severe embryonic growth retardation

Question 10

what is isodisomy?

Answer 10

uniparental disomy where two copies of the exact chromosome are inherited from one parent

Question 11

how does isodisomy happen?

Answer 11

nondisjunction in meiosis II then trisomy rescue after fertilization

Question 12

what is heterodisomy?

Answer 12

inheriting both homologs from a single parents

Question 13

how does heterodisomy occur?

Answer 13

nondisjunction in meiosis I then trisomy rescue after fertilization

Question 14

how could you see chromosome mosaicism of trisomy 15 or 16, with respect to trisomy rescue?

Answer 14

trisomy rescue occurs as late post-zygotic event

Question 15

how can you see confined placental mosaicism in trisomy 15 or 16 with respect to trisomy rescue?

Answer 15

if trisomy rescue occurs as an early post-zygotic event then only placental cells are trisomic

Question 16

what are the clinical features of prader willi syndrome

Answer 16

hypotonia
failure to thrive in infancy
obesity after 2 yrs
behavior and mild MR
obsession w/ food
small hands and feet
short stature
small genitals and undescended testes

Question 17

which parentally derived chromosome do prader willi patients lack?

Answer 17

paternally derived

Question 18

what are three ways one can lack a paternally derived chromosome

Answer 18

1. deletion of paternal 15q11-q13
2. maternal uniparental disomy followed by loss of paternal chromosome by trisomy rescue
3. mutation in father’s imprinting center so female imprint persists

Question 19

angelman clinical features?

Answer 19

prominent jaw
wide mouth
no speech
severe MR
spasticity
seizures
ataxia
inappropriate laughter

Question 20

what parentally derived chromosome do angelman patients lack?

Answer 20

maternal copy

Question 21

what are 4 ways you can lack a maternal chromosome in angelman?

Answer 21

1. deletion of 15q11-q13
2. paternal UPD
3. mutation in mother’s imprinting center so male imprint persists
4. single gene loss of fxn mutation in maternal UBE3A