Non-Mendelian Inheritance Flashcards
(19 cards)
MELAS
- Mitochondrial Inheritance
- Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes
- Hearing loss, diabetes, seizures, intellectual disability, cardiomyopathy
Heteroplasmy
Mixture of normal and abnormal mitochondrial DNA
Homoplasmy
All mitochondrial DNA is the same
Threshold Effect
A certain percentage of abnormal mitochondrial DNA is tolerated without symptoms
- Clinical phenotype may vary depending on the percentage of abnormal mtDNA
- Threshold varies depending on individuals and tissue types
Trinucleotide Repeat Disorders
- Present throughout the genome
- Stable during mitosis and meiosis
- Sequence copy number is transmitted as polymorphism from parent to child
- Increase in severity or earlier onset of a phenotype over successive generations
- Formation of hairpin loop is a possible explanation for the expanded DNA replication product
Myotonic Dystrophy
-CTG Repeat
-Affects skeletal and smooth muscle as well as eye, heart endocrine system, and CNS
-Myotonia: sustained muscle contraction (extended firm hand shake)
-3 phenotypes:
Mild (Cataract and mild myotonia; Normal lifespan)
Classic (Muscle weakness and wasting, cataract, myotonia; possible shortened life span)
Congenital (Severe congenital hypotonia)
Fragile X Syndrome
- CGG Repeat in FMR1 gene on X chromosome
- Most common inherited cause of intellectual disability
- Long face, large ears
- Full mutation occurs upon complete methylation of FMR1 gene
Mosaicism
Presence of more than one cell line in an individual; could be somatic or gonadal
Somatic Mosaicism
- Usually caused by post-zygotic mutation
- Variable degree of disease severity
Mosaic Down Syndrome
- May be less severely affected than with full trisomy 21
- Phenotype/severity depends on proportion of cells with trisomy 21 in each tissue type
Pallister-Killian Syndrome
- Mosaic Tetrasomy 12p
- Low muscle tone, characteristic facies, high arched palate, hypopigmentation, extra nipples, developmental delays, and diaphragmatic hernias
Gonadal Mosaicism
- Individual unaffected w/ syndrome
- Mutation occurred in precursor sperm or egg
Imprinting
Different epigenetic modification of the maternal paternal genetic contributions to the zygote
- Some genes are expressed preferentially from the maternal or paternal alleles
- Differences in phenotype when; uniparental disomy, heterozygous deletion or mutation for an imprinted region of a chromosome or gene
- ie. Triploidy
Cystic Fibrosis
- Uniparental Disomy (UPD)
- Explanations:
- Non-paternity
- De novo mutation
- Large deletion on paternal chromosome
- Maternal uniparental disomy
Russel-Silver Syndrome
-Growth disorder with prenatal onset
-small triangular face with distinctive facial features
~10% cases due to maternal UPD of chromosome 7
Prader-Willi Syndrome
- UPD of chromosome 15 from the MOTHER
- Hypotonia, Intellectual Disability, Hyperphagia (pathological overeating)
- Lack of expression from chromosome 15 genes that are normally only expressed from the Paternal allele
Angelman Syndrome
- UPD of chromosome 15 from the FATHER
- Severe intellectual disability, movement disorder, and seizures
- Lack of expression from chromosome 15 genes that are normally only expressed from the MATERNAL allele
Heterodisomy
- Non-disjunction occurs in Meiosis I
- Gametes have a pair of homologous chromosomes
Isodisomy
- Non-disjunction occurs in Meiosis II
- The non-disjunction will produce a gamete with two identical copies of a homolog chromosome
