Genetic Basis of Complex Inheritance Flashcards
What does mendelian inheritance involve
The Law of Dominance
The Law of Segregation
The Law of Independent Assortment
What are the principles of non-mendelian inheritance
Does not fit in with Mendelian’s Law (e.g.
Gene conversion or Intermediate phenotype)
What kind of non-mendelian inheritance patterns are there
Incomplete Penetrance
Genomic Imprinting
Extranuclear Inheritance
Anticipation
What mechanisms cause incomplete penetrance
Environmental factor
Genetic Modifiers
What mechanisms cause genomic imprininting
Variants from parents
What mechanisms cause extranuclear inheritant
e.g. mitochondria mutations
What mechanisms cause anticipation
e.g. triplet repeat expansion
What is penetrance
The frequency with which a trait is manifested by individuals carrying the gene
What mutation causes cystic fibrosis (CF)
Mutation in CFTR
Autosomal recessive inheritance
What is the prevalence of CF in European Caucasians
1 in 2,500 (4% carriers)
What is the prevalence of CF in Africans
1 in 13,000
What is the prevalence of CF in Asians
Rare
How can the CF phenotype be variable
In severity and affected organs
What organs can be affected in CF
Sinuses (sinusitis infection) Lungs Skin Liver Pancreas Intestines Reproductive organs
How are the lungs, skin, liver. pancreas and intestines affected in CF
Lungs - thick sticky mucus build up, bacterial infection and widened airways
Skin - sweat glads produce salty sweat
Liver - blocked biliary ducts
Pancreas - blocked pancreatic ducts
Intestines - cannot fully absorb nutrients
What are gene modifiers
Genes that have small quantitative effects on the level of expression of another gene
It may involve polymorphism
What environmental factors can affect the severity of CF in organs
Lifestyle Diet Smoke Alcohol Drug Stress Air pollution Chemicals Infection
What else apart from genetic factors can explain the prevalence of increased diabetes
Rapid changes in lifestyle and risk factors such as:
Obesity
Unhealthy diets
Physical inactivity
What factors are seen in genetic diseases
Rare
Genetics simple
Uni-factorial
High recurrence rate
What factors are seen in enviromental diseases
Common
Genetics complex
Multi-factorial
Low recurrence rate
Give some examples of human diseases mainly caused by genetics
Haemophilia
Osteogenesis imperfecta
Huntington’s Disease
Familial motor neurone disease
Give some examples of human diseases caused by both genetics and environmental factors
Manic depressive psychosis
Ischaemic heart disease
Ankylosing spondylitis
Peptic ulcer Diabetes
Give some examples of human diseases mainly caused by enviromental factors
TB
Scurvy
What is genomic imprinitng
Genes expressed from only one chromosome
Parent-of-origin dependent
What is 5’ Methylcytosine (mC)
Occurs from DNA methylation of cytosine
It induces the structural adaptation of chromosomal region so as to perpetuate altered activity states
What genetic mechanisms of error are there
Deletions
Point mutations
Imprinting errors
Uniparental disomy
What is uniparental disomy
Inheritance of a chromosome pair from one parental origin
How can uniparental disomy occur
From:
Non-disjunction of a trisomy zygote
Duplication of a monosomy zygote
Non-disjunction or duplication of disomy zygote
What does the recombination of a zygote formed from gamates that have undergone mitotic error produce
Partial uniparental disomy
What can uniparental diploidy cause
Gynogenic
Androgenic
Describe gyongeic
2 maternal genomes
Mass of embryo
Ovarian teratoma
Describe androgenic
2 paternal genomes
Mass of placenta
Hydatidiform mole
What chromosomal region is affected in angelman syndrome and prader-willi syndrome
15q11-13
What does angelman syndrome cause
Epilepsy Mental retardation (severe) Awkward gait Inappropriate laughter
What does prader-willi syndrome cause
Hypotonia Mental retardation (mild-moderate) Short stature Marked obesity
What causes angelman syndrome
Deletion of maternal region
Paternal UPD
Imprinting defect
Point mutations
What causes prader-willi syndrome
Deletion of paternal region
Maternal UPD
Imprinting defect
How is mitochondria inherited
Maternal egg contains mitochondria
Paternal mitochondria degrades upon fertilisation
Thousands of maternal mitochondria is replicated per cell
Describe mitochondrial genetics
Circular form 16.6 kb 37 genes 2 rRNA 22 tRNA 13 coding genes
Why is the mitochondria a mutation hotspot
Lack of efficient DNA repair system
Lack of protective proteins, such as histones
Damaged can be caused by reactive oxygen species (ROS), such as free radicals
What is homoplasmy
Uniform mtDNA - no disease
What is hetrtoplasmy
2 or more mtDNA
If low % mutation - no/mild disease
High % mutation - disease
What is a myopathy
Disease of muscle tissue
What are the 3 major myopathies that can occur in mitochondrial disease
Myoclonic epilepsy with ragged red fibers (MERRF)
Mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptons (MELAS)
Chronic progressive external ophthalmoplegia (CPEO)
What other conditions can be caused by mitochondrial disease
Leber’s hereditary optic neuropathy (LHON) - loss of central vision
Leigh’s syndrome - encephalopathy
Diabetes mellitus and deafness (DAD)
How is a three parent embryo produced
Healthy DNA removed from patients egg cell excluding faulty mitochondria
Patients DNA transplanted into donor egg with healthy mitochondria
Reconstructed egg fertilised with sperm in lab and implanted into patient
When does anticipation present
Disease presents at earlier age and/or increasing severity in succeeding generations
Give examples of anticipation diseases
Triplet repeat diseases e.g. Huntington’s disease Myotonic dystrophy Fragile X syndrome
What gene is mutated in Huntington’s disease and how many repeats tend to be found
Huntingtin
Repeat: (CAG)n
Normal: 11 - 34
Mutant: 36 - 120
What gene is mutated in Myotonic dystrophy and how many repeats tend to be found
DMPK
Repeat: (CTG)n
Normal: 5 - 30
Mutant: 50 - 2000
What gene is mutated in Fragile X syndrome and how many repeats tend to be found
FMR1
Repeat: (CGG)n
Normal: 6 - 50
Mutant: 60 - 1000
