UPD

Question 1

What mechanisms can cause an imprinting disorder

Answer 1

1) UPD of imprinted region.
2) Deletion: del of gene or del of ICR
3) Duplication: ↑ expression of imprinted genes
4) Mutation on active allele
5) Epimutation: hypomethylation / hypermethylation @ ICR alters expression of imprinted gene.

Question 2

Name 2 imprinting disorders

Answer 2

Prader-willi
Angelmans
Beckwith weideman
Russell silver
Transient neonatal diabetes
UPD 14 mat/pat
UPD 20

Question 3

What causes a complete hydatidiform mole

Answer 3

UPDpat diploid complement

Question 4

What causes a partial hydatidiform mole

Answer 4

triploidy (46 of pat origin)

Question 5

What’s causes a benign cystic ovarian teratoma

Answer 5

UPDmat diploid complement

Question 6

What disorder is associated with a segmental UPD

Answer 6

Beckwith weideman 15-20% cases

Question 7

For carrier of structural rearr, rob, reciprocal translocation what are the mechanisms that cause a risk of UPD

Answer 7

postzygotic correction of an interchange trisomy.
monosomy rescue of monosomy from a 3:1 segregation
Acrocentric chrom isochrom formation.

Question 8

What are the mechanisms for complete chromosome UPD

Answer 8

Gamete complementation
Trisomy rescue **
Monotony rescue
Mitotic error

Question 9

Describe gamete complementation

Answer 9

Mitotic NDJ in both parents results in a disomic gamete from one parent & a nullisomic gamete for the same chrom from the other parent.

result in a diploid zygote with UPHD

Question 10

Describe trisomy rescue

Answer 10

Mitotic NJD in one parent results in a disomic gamete.
Fertilisation of a haploid gamete results in a trisomic conceptus.

Rescue͟ through loss of one homologue (perhaps anaphase lag)
at a very early postzygotic stage (poss in zygote)

UPD in 1/3 cases.
Meiosis I nondisjunction :UPHD
Meiosis II nondisjunction :UPID

Question 11

Describe monosomy rescue

Answer 11

Meiotic NDJ results in a nullisomic gamete.
Fertilisation with a haploid gamete : monosomic conceptus.

Rescue͟ through mitotic NDJ/ mitotic misdivision leads to isochrom formation or duplication

In this case the UPD would be an isodisomy.

Question 12

Name two different methods for detecting UPD

Answer 12

Methylation specific methods: Southern blotting, MLPA
Microsatellite analysis
Bisulphate modification methods: MS-PCR, PCR & restriction analysis, melts curve analysis, pyrosequencing
SNP array
WES /WGS

Question 13

What’s an imprinting disorder

Answer 13

Disorder arising from the altered expression/function of an imprinted gene/ collection of genes