Uniparental Disomy Flashcards
What is uniparental disomy and how is it believed to come about?
Inherit both homologs from one parent. Thought to result from chromosome loss from originally trisomic fetus, which is normally fatal, hence the name “Trisomy Rescue”.
Why does uniparental disomy often cause disease?
Because there is imprinting of many genes on each chromosome.
What are the two types of uniparental disomy?
Heterodisomy- two different homologues from one parent– a meiosis I error
Isodisomy- two copies of the same chromosome (formerly sister chromatids) from one parent (i.e. two copies of the same homologue)– a meiosis II or early mitosis error.
Can heterodisomy, idodisomy, or both cause the following problems:
1) Autosomal recessive disease from one carrier parent.
2) Affected female for X-linked recessive traits.
3) Imprinted genetic disorders.
4) Father to son transmission of X-linked trait.
1) Isodisomy
2) Isodisomy (from carrier mom)
3) Both
4) Heterodisomy (X and Y from father)
Which of the following are not symptoms/charactersitics of Miller-dieker syndrome? Microcephaly Lissencephaly Broad forehead Delayed developmental milestones Truncal hypotonia Upper and lower limb flacidity Decreased tendon reflexes with negative Babinski sign No response to hand-clapping beside the ears Areas of agyria on brain MRI Decreased white matter Expanded ventricles EEG abnormal and consistant with siezures Heart malformations Gastroesophageal reflux Almost all die by age 2
Decreased white matter and expanded ventricles are not observed.
You see upper and lower limb spacticity, not facidity.
You see Increased tendon reflexes with Clonus, not negative Babinski
Which of the following does Miller-Dieker not display? Peliotropy Haploinsufficiency Contiguous gene syndrome allelic heterogenicity
Allelic heterogenicity
What is contiguous gene syndrome and what is the mutation in Miller-Dieker Syndrome?
Contiguous gene syndrome results from loss of several genes near each other on a chromosome. Deletion of 17p13.3 results in Miller-Dieker Syndrome.
Describe the mutation that causes lissencephaly.
Lissencephaly is due to loss of one copy of LIS1 gene, which encodes the non-catalytic subunit of platelet-activating factor acetylhydrolase (PAFAH), the protein that interacts with cytoplasmic dynein in order to produce cell migration.
True or false: the facial features seen in Miller-Dieker Syndrome result from loss of genes in the 17p13.3 deletion.
False: the facial features result from loss of other genes.
__% of Miller-Dieker patients have a visible deletion in 17p, and >__% have deletion via FISH with MD probe.
70%
90%
What percent of MD deletions are de novo and what is the recurrence risk for de novo deletions?
80%
<1%
What percent of MD mutations are from balanced reciprocal translocation in a heterozygous carrier parent?
20%
22% pregnancy loss; 33% have some phenotype including MDS, dupe17p [–> CMP from duplicated PMP22]
Name three other gene mutations that cause lissencephaly.
LIS1, DCX, XLAG, and Reln (reelin)
