Lecture 17

Question 1

Mitochondrial inheritance

Answer 1

Affected mom transmits to all her offsprins

Question 2

Heteroplasmy

Answer 2

The severity of the disorder depends on the number of mitochondria that have the mutant gene
Variable expression

Question 3

Example of mito inheritance and heteroplasmy 3

Answer 3

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)
MERRF
Leber hereditary optic neuropathy

Question 4

Digenic disorder example 1

Answer 4

Retinitis pigmentosa

Mutation in 2 independent genetic loci, heterozygous for gene A and B

Question 5

Imprinting

Answer 5

Methylation of specific loci (epigenic change) and silencing of the gene
On chromosome 15:
SNRPN inactive, UBE3A active in maternal
UBE3A inactive, SNRPN active in paternal

Question 6

Prader Willi Syndrome 2 causes

Answer 6

1. Microdeletion of paternal SNRPN, so no SNRPN (70% of case)
2. Maternal uniparental disomy of chromosome 15, also no SNRPN since SNRPN is inactive in maternal

Question 7

Angelman syndrome 2 causes and symptoms

Answer 7

1. Paternal uniparental disomy for chromosome 15, no production of UBE3A
2. Deletion of maternal chromosome 15q11-13

Therefore, no active UBE3A

Severe intellectual disability, seizures
Puppet like posture
“Happy puppet syndrome”

Question 8

Methylation analysis

Answer 8

Methylation sensitive restriction enzyme does not cleave methylated maternal DNA but cleaves paternal chromosome 15
Followed by Southern blot, PCR, and DNA sequencing

Question 9

4 classes or triplet repeat disorders

Answer 9

1. At the promoter region of the gene-reduced expression (CGG repeat in Fragile X syndrome)
2. In an intron-heterochromatin (Friedrich ataxia)
3. In the coding region of the gene-polyglutamine expansion in the protein (Huntington disease: CAG codes)
4. 3’-UTR-myotonic dystrophy

Question 10

Anticipation

Answer 10

Disease develop at earlier age and greater severity
Greater number of repeats, earlier onset
Repeats are unstable

Question 11

Anticipation 3 disorders

Answer 11

Huntington disease (AD)
Myotonic dystrophy (AD)
Fragile X syndrome (x-linked) repeat expansion in mom

Question 12

Diagnostic tests for Fragile x syndrome

Answer 12

Southern blot
Cytogenetic test: fragile site demonstrated in a folate deficient medium
Analysis of mother’s x chromosome: premutation