The Genetic Basis of Complex Inheritance Flashcards
What are the 3 laws that fall under medelian inheritance?
- The law of dominance
- The law of segregation
- The law of independent assortment
What is included in non-mendelian inheritance?
- gene conversion
- intermediate phenotype
What inheritance patterns are seen in non-mendelian inheritance and what mechanism brings them about?
- Incomplete penetrance: environemental factors and genetic modifiers
- Genomic imprinting: variants from parents
- Extranuclear Inheritance: mitochondria mutations
- Anticipation: triple repeat expansion
What is penetrance?
the frequency with which a trait is manifested by individuals carrying the gene
What is the risk calculation?
Penetrance of mutant over penetrance of wild type
How can the CF phenotype vary?
In severity and organs affected
What are genetic modifiers?
Genes that have small quantitative effects on the level of expression of another gene
What are environmental factors?
- lifestyle
- diet
- smoke
- alcohol
- drugs
- stress
- air pollution
- chemicals
- infection
How can genetic diseases be described?
- rare
- genetics simple
- uni-factorial
- high recurrence rate
How can environmental diseases be described?
- common
- genetics complex
- multi-factorial
- low recurrence rate
What is genomic imprinting?
Genes expressed from only one chromosome and is parent of origin dependent
What are epigenetic modifications?
Heritable changes in gene function that cannot be explained by changes in DNA sequences
What genetic mechanisms can be involved in inheritance?
- deletions
- point mutations
- imprinting errors
- uniparental disomy
What are the 2 different types of uniparental diploidy?
- gynogenic
- androgenic
Describe gynogenic uniparental diploidy.
- 2 maternal genomes
- mass of embryo
- ovarian teratoma
Describe androgenic uniparental diploidy.
- 2 paternal genomes
- mass of placenta
- hydatidiform mole
What are 2 examples of imprinting disorders?
- Angelman syndrome
- Prader Willi syndrome
Describe Angelman syndrome.
- epilepsy
- severe mental retardation
- awkward gait
- inappropriate laughter
Describe Prader-Willi syndrome.
- hyptonia
- mild-moderate mental retardation
- short stature
- marked obesity
What chromosomal region do AS and PWS occur in?
15q11-13
What are the characteristics of a mutation hotspot?
- lack of efficient DNA repair system
- lack of protective proteins such as histones
- damaged by reactive oxygen species such as free radicals
What is polyploidy?
Up to thousands of mitochondria per cell,
What is homoplasmy
A cell that has uniform collection of mtDNA and presents no disease
What is heteroplasmy?
When a cell has some mitochondria that have a mutation in the mtDNA and some that do not. If there is ahigh percentage of mutation disease can occur.
What does mitochondrial disease do?
affects tissue with high metabolic demand
What are the 3 major myopathies of mitochondrial disease?
- Myoclonic epilepsy with ragged red fibres(MERRF)
- Mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like symptoms (MELAS)
- Chronic progressive external opthalmoplegia (CPEO)
What other mitochondrial disease are there?
- Leber’s hereditary optic neuropathy (LHON) causes loss of central vision
- Leigh’s syndrome causes encephalopathy
- Diabetes meliituse and deafness (DAD)
What is anticipation?
The disease presents at earlier age and/ or increasing severity in succeeding generations
What are 3 examples of diseases which exhibit anticipation?
- Huntington’s
- Myotonic dystrophy
- Fragile X syndrome
