Genetic Basis of Complex Inheritance Flashcards
What are the 3 laws of mendelian inheritance?
Dominance
Segregation
Independent Assortment
What mechanisms cause incomplete penetrance?
Environmental
Genetic modifiers
What mechanisms cause genomic imprinting?
Variants from parents
What mechanisms cause extranuclear inheritance?
Mitochondria mutations
What mechanisms cause anticipation?
Triplet repeat expansion.
Define penetrance.
Frequency with which a trait is manifested by individuals carrying the gene.
What is the penetrance of cystic fibrosis?
100%
What is the penetrance of breast cancer?
70-80%
What is allele frequency?
The variation of alleles in a population.
What is cystic fibrosis caused by?
Mutation in CFTR (Autosomal recessive).
What is the prevalence in european caucasians?
1 in 2500
What two phenotypes are variable in cystic fibrosis?
Severity
Affected organs
What builds up in cystic fibrosis?
Mucus
What are genetic modifiers?
Genes that have small quantitative effects on the level of expression of another gene.
What are included in environmental factors?
Lifestyle Diet Smoke Alcohol Drug Stress Air pollution
What does polymorphism mean?
May occur in different forms, i.e cystic fibrosis can have different forms which is why it affects people differently.
What are the 4 features of genetic factors?
Rare
Simple
Uni-factorial
High recurrence
What are the 4 features of environmental factors?
Common
Complex
Multi-factorial
Low recurrence
What is genomic imprinting?
Genes expressed from only one chromosome.
What is genomic imprinting dependent on?
Parent-of-origin.
What are epigenetic modifications?
Heritable changes in gene function which can’t be explained by changes in DNA sequences.
What are deletions, point mutations, imprinting errors and uniparental disomy examples of?
Genetic mechanisms
Why do imprinted genes have a higher risk of disease?
Expression is only from a single copy
What is uniparental disomy?
Inheritance of a chromosome pair from one parental origin.
What happens during UPD trisomy rescue?
Nondisjuction
What happens during UPD monosomy rescue?
Duplication
What happens during UPD mitotic error?
Nondisjuction/duplication
Recombination
What is the name of UPD with 2 maternal genomes?
Gynogenic
What is the name of UPD with 2 paternal genomes?
Angrogenic
What forms in gynogenic UPD?
Ovarian teratoma (Non-malignant)
What forms in androgenic UPD?
Hydatidiform mole
What two disorders come from chromosomal region 15q11-13?
Angelman Syndrome
Prader-Willi Syndrome
Why can two different disorders come from the same chromosomal region?
Parental and maternal differentiation.
Where do we usually inherit mitochondria from?
Mother
What type of form is mitochondria?
Circular
How many genes do mitochondria have?
37
2rRNA, 22tRNA, 13 coding regions
Why do mitochondria have a higher mutation rate?
Lack of efficient DNA repair
Lack of protective proteins
Damaged by ROS (free radicals)
What is the disease chance in homoplasmy?
No disease
What is the disease chance in heteroplasmy?
No/mild disease
Disease
How many mitochondria are in cells?
Up to thousands
What type of tissues do mitochondrial diseases affect?
Tissues with high metabolic demand.
What are the 3 major myopathies?
MERRF
MELAS
CPEA
What is Leigh’s syndrome?
Encephalopathy
How did a three-parent baby work?
Nucleus from mother put into patient’s egg. Patient’s egg fertilised by father’s sperm.
What is anticipation?
Disease presents at earlier age and/or increasing severity in succeeding generations.
What are 3 examples of triplet repeat diseases?
Huntingtons’s
Myotonic dystrophy
Fragile X Syndrome
