UPD and imprinting

What is UPD isodisomy? and what causes it?

both homologs are identical.
caused by nondisjunction at meiosis II or mitotic error

causes of UP

gamete complementation, trisomic rescue, monosomic rescue, mitotic error

interchange 3:1 segregation

full autosomal trisomy or full monosomy

if a parent is a carrier of a balanced or rob translocation, asymmetric segregation of the chromosomes could lead to _________________ ____________. This could result in the __________ chromosome and one of the ___________ homologs being transmitted into the fetus and post-zygotic correction could result in ______

-interchange trisomy
-derivative
-normal
-UPD

in the case of an acrocentric chromosome with a parent who has a rob t, the chromosome could replicate as a(n) _______________ and has been reported in UPDs for chromosomes ______, _______, and ______

-isochromosome
-13, 14, and 15

how does segmental UPD arise and where does the segment lay on the chromosome?

caused by post zygotic somatic recombination and the segment lies distally. The rest of the chromosome will have normal biparental inheritance

phenotypes caused by UPD

IUGR/post natal growth retardation, ID, congenital defects, dysmorphia

UPD isodisomy can cause _________ of an AR gene

homozygosity

what does UPD look like on karyotype

normal karyotype

what do polymorphic DNA markers show with UPD isodisomy

markers show both homologs with the same haplotype from one parent.
large runs of homozygosity spanning most or all of the affected chromosome

what is UPD heterodisomy

different homologs

what do polymorphic DNA markers show with UPD heterodisomy

2 chromosomes that have the same haplotypes as the chromosome pair form one parent

cause of UPD heterodisomy

nondisjunction at meiosis I

define epigenetics/imprinting

same genotype will produce a different phenotype depending on the sex of the transmitting parent due to methylation error

imprinting mechanisms function _____________________

mono-allelically (meaning, when imprinting happens, only the paternal OR maternal segment will be active)

what happens of both imprinted segments originate from one parent

there would be either double the amount of expression or no expression at all, resulting in the phenotypic defects seen in people with UPD

What does paternal UPD of all 46 chromosomes cause

complete hydatidiform mole

what does maternal UPD of all 46 chromosomes cause

benign teratoma (type of ovarian cyst)

what forms from one maternal and two paternal chromosome complements

triploid fetus

what is gamete complementation

This is when you have a gamete with two copies of a chromosome (should have only one), and it gets fertilized with a gamete that happens to have no copies of that chromosome.

what is the most common mechanism that causes UPD and how does it work

trisomic rescue:
a trisomy that looses the extra chromosome, restoring the zygote to disomy. when the wrong chromosome is lost, this can cause maternal or paternal UPD

what is monosomic rescue and how does it work

monosomic zygote (only one copy of a particular chromosome – the other parent’s dropped out), and that chromosome duplicates itself. replication of the normal homolog can cause UPD isodisomy

what is mitotic error

normal conception that leads to trisomy or monosomy.
trisomy: the wrong chromosome is lost producing either maternal or paternal UPD
monosomy: the chromosome is duplicated

what are some rare mechanisms that cause UPD

- correction of interchange trisomy
- correction of interchange monosomy
- isochromosome formation
- correction of imbalance due to extra structurally abnormal chromosomes.

tertiary 3:1 segregation

trisomy or monosomy dependent on combined content of the der chromosomes
causes tertiary trisomy, tertiary monosomy

what does a karyotype look like when there is a segmental UPD

normal karyotype

examples of conditions that can be caused by segmental UPD

BWS, russell sliver syndrome, transient neonatal diabetes (TNDM)

condition that comes from UPD on chromosome 6

transient neonatal diabetes (TNDM)

condition that comes from UPD of chromosome 7

russell silver syndrome

condition that comes from UPD of chromosome 11

BWS

conditions that comes from UPD/imprinting/deletion on chromosome 15

PWS
AS

majority of PWS and AS cases are caused by _________ on chromosome 15

deletions

PWS is caused by ___ deletion, while AS is caused by a ___ deletion

PWS= paternal deletion

AS= maternal deletion

what gene is usually effected in AS

UBE3A

what gene is usually effected in PWS

SNRPN