Complex inheritance

Question 1

Examples of non-Mendelian inheritance

Answer 1

• Gene conversion
• Incomplete penetrance
• Genomic inprinting
• Extranuclear inheritance
• Anticipation

Question 2

Inheritance penetrance

Answer 2

Mechanisms: environmental factor, genetic modifiers

Question 3

Genomic imprint mechanisms

Answer 3

• An epigenetic process
• Variants from parents, dependent on that parent
• Genes expressed from only one chromosome
• If an inherited allele from a parent is imprinted, it is silenced
• Only the allele from the other parent is expressed

Question 4

Genomic imprinting can result in

Answer 4

• Deletions
• Point mutations
• Imprinting errors
• Uniparental disomy

Question 5

Imprinting errors examples

Answer 5

• Angelman and Prader-Willi, same chromosomal region. Totally different syndromes

Question 6

Angelman syndrome

Answer 6

• Epilepsy
• Severe mental retardation
• Awkward gait
• Inappropriate laughter
• Deletion on maternal chromosome or paternal UPD

Question 7

Prader-Willi Syndrome

Answer 7

• Hypotonia
• Mental retardation (mild to moderate)
• Short stature
• Obesity
• Deletion on paternal side or maternal UPD

Question 8

Uniparental disomy

Answer 8

• Inheritance of a chromosome pair from one parental origin

Question 9

Effects of uniparental diploidy

Answer 9

• Gynogenic: 2 maternal genomes, mass of embryo, ovarian teratoma
• Androgenic: 2 paternal genomes, mass of placenta, molar pregnancy

Question 10

Extranuclear inheritance

Answer 10

Mechanism:

• Mitochondria mutation due to higher mutation rate in mitochondria
• Lack of efficient DNA repair
• Lack of protective proteins, histones
• Damaged by free radicals

Question 11

3 major myopathies

Answer 11

• Myoclonic epilpepsy with ragged red fibres (MEERF)
• Mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptoms (MELAS)
• Chronic progressive external opthalomoplegia (CPEO)

Question 12

Non-myopathic diseases from extranuclear inheritance

Answer 12

• Leber’s hereditary optic neuropathy - loss of central vision
• Leigh’s syndrome - encephalopathy
• Diabetes mellitus and deafness (DAD)

Question 13

Anticipation

Answer 13

Mechanism:

• Triplet repeat expansion
• Disease present at earlier age and/or increasing severity in succeeding generations
  e. d. Huntington’s, Myotonic dystrophy, Fragile X syndrome

Question 14

Genetic penetrance definition

Answer 14

• Frequency with which a trait is manifested by individuals carry the gene

Question 15

Cystic fibrosis

Answer 15

• Autosomal recessive
• CF phenotype is variable in terms of severity and affected organs
• Genetic modifiers: may involve polymorphism
• Environmental factors: lifestyle, diet, smoking, alcohol/drugs, stress, air pollution, infection

Question 16

Genetic conditions are:

Answer 16

• Rare
• Genetics simple
• Uni-factorial
• High recurrence rate

Question 17

Environmental conditions are:

Answer 17

• Common
• Genetics complex
• Multi-factorial
• Low recurrence rate