Imprinting Flashcards
what is the mechanism of imprinting?
covalent modification of DNA
either cytosine –> 5-methylcytosine OR
histone modification
How is imprinting important for fetal development?
the paternal genome is important for extraembryonic development
the maternal genome is important for fetal development
what are the two types of hydatidiform moles?
complete - no fetus or placenta
partial - remnants of placenta and atrophic fetus
what is the genotype of a complete mole?
46,XX
uniparental disomy
how does a paternally derived mole get all chromosomes from dad?
endoduplication - haploid sperm fertilizes empty ovum and duplicates its chromosomes
dispermy - two sperm fertilize one egg
what is the consequence of paternally derived hydatidiform mole?
trophoblast hyperplasia with absent/disorganized fetus
what is the genotype of a partial hydatidiform mole?
69,XXY or 69,XXX
what is the consequence of paternally derived partial hydatidiform mole?
abundant trophoblast development, poor embryo development
what is the consequence of maternally derived hydatidiform mole?
small fibrotic placenta, severe embryonic growth retardation
what is isodisomy?
uniparental disomy where two copies of the exact chromosome are inherited from one parent
how does isodisomy happen?
nondisjunction in meiosis II then trisomy rescue after fertilization
what is heterodisomy?
inheriting both homologs from a single parents
how does heterodisomy occur?
nondisjunction in meiosis I then trisomy rescue after fertilization
how could you see chromosome mosaicism of trisomy 15 or 16, with respect to trisomy rescue?
trisomy rescue occurs as late post-zygotic event
how can you see confined placental mosaicism in trisomy 15 or 16 with respect to trisomy rescue?
if trisomy rescue occurs as an early post-zygotic event then only placental cells are trisomic
what are the clinical features of prader willi syndrome
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
which parentally derived chromosome do prader willi patients lack?
paternally derived
what are three ways one can lack a paternally derived chromosome
- deletion of paternal 15q11-q13
- maternal uniparental disomy followed by loss of paternal chromosome by trisomy rescue
- mutation in father’s imprinting center so female imprint persists
angelman clinical features?
prominent jaw wide mouth no speech severe MR spasticity seizures ataxia inappropriate laughter
what parentally derived chromosome do angelman patients lack?
maternal copy
what are 4 ways you can lack a maternal chromosome in angelman?
- deletion of 15q11-q13
- paternal UPD
- mutation in mother’s imprinting center so male imprint persists
- single gene loss of fxn mutation in maternal UBE3A
