Genetics 2

Question 1

What are the 3 non mendelian patterns of inheritance?

Answer 1

• anticipation (nucleotide repeat disorders)
• mitochondrial
• multifactorial

Question 2

What is anticipation? what is it due to? how many disease follow this pattern? when does the repeat occur more often in fathers? mothers?

Answer 2

• some genetic diseases have an earlier age of onset, or increased severity in more recent generations
• due to dynamic mutations- expansion of trinucleotide repeats
• more than 20 diseases follow this pattern
• when repeats is in an exon, expansion occurs is father
• when in UTR, expansion occurs in mother

Question 3

What is huntingtons disease? penetrance? symptoms? treatment?

Answer 3

• anticipation pattern
• autosomal dominant disorder
• penetrance near 100%
• progressive neurodegeneration causing slowly progressive movement disorder with intellectual impairment and psychiatric disturbance, dementia
• no treatment or cure

Question 4

Cause of huntingtons disease? what do longer repeats correlate with? function of protein?

Answer 4

exonic polyglutamine expansion in huntington protein:

• e 40 repeats fully penetrant
• longer repeats correlate with earlier onset
• normal function of this protein is unclear
• expanded proteins forms inappropriate aggregates with other proteins (gain of function)

Question 5

What is myotonic dystrophy? symptoms?

Answer 5

• most common muscular dystrophy in adults
• autosomal dominant
• progressive muscle deterioration
• myotonia
• cardiac arrhythmia
• testicular atrophy
• insulin resistance
• cataracts

Question 6

Causes of myotonic dystrophy? severity? age of onset? repeat number?

Answer 6

Expansion of 3’ UTR of affected gene (RNA gain of function)
-severity increases and age of onset decreases through generations

• repeat number correlates with severity:
• 5-37 = unaffected
• 50-100 = mild
• 100-1000s= full disease

-large repeats transmitted almost exclusively by females

Question 7

Who is mitochondria inherited from? why?

Answer 7

• mother
• b/c mitochondria are located in the cytosol
• affects males and females equally

Question 8

heteroplasmy in mitochondria?

Answer 8

• b/c each cell has a population of mtDNA molecules, a single cell will have some that carry a mutation and some that do not
• this causes a great deal of variability in expression of mitochondrial diseases
• mutation severity varies too

Question 9

which tissues are affected more severely by mitochondrial diseases?

Answer 9

tissue with higher ATP requirements are most often and severely affected
-CNS consumes 20% of ATP produced in body

Question 10

Which has a higher mutation rate: mtDNA or nuclear DNA?

Answer 10

mitochondrial

Question 11

What is Leber hereditary optic neuropathy (LHON)? symptoms? when does it begin?

Answer 11

• mitochondrial disease
• rapid loss of vision in central field due to death of optic nerve
• begins in 3rd decade of life
• usually irreversible
• heteroplasmy minimal, expression relatively uniform in affected families

Question 12

What is MELAS? when does it present? symptoms?

Answer 12

• mitochondrial encephalopathy, lactic acidosis, stroke like episodes
• mitochondrial inheritance
• may present at any time in life
• progressive neurological deterioration and seizures
• wide range of expression, even in same family

Question 13

What is kearns sayre syndrome (KSS)? symptoms?

Answer 13

• mitochondrial

- muscle weakness, cerebellar damage, heart failure

Question 14

What is MERRF?

Answer 14

• myoclonic epilepsy, ragged red fibers in muscle, ataxia, sensorineural deafness
• mitochondrial

Question 15

What is retinas pigments? genes? symptoms? cause?

Answer 15

• mitochondrial
• most common inherited cause of blindness
• locus heterogeneity (45 different genes)- results in different patterns of inheritance in different families, some cases due to mt mutations
• begins with night blindness and progresses to daytime vision
• most are legally blind by age 40
• pigments deposited on retinal surface as pathological changes accumulate

Question 16

What are multifactorial inherited diseases? how are they inherited?

Answer 16

-products of varying genetic and environmental influences

• many of the most common disorders:
• diabetes
• hypertension
• heart disease
• obesity
• cancer

-some traits tend to cluster in families, but are not transmitted in mendelian fashion

• congenital abnormalities:
• cleft lip and palate
• spina bifida
• pyloric stenosis

Question 17

What is polygenic inheritance? what does it work best for? cause?

Answer 17

• assumes that many genes are involved, with little or no environmental influence
• works best for quantitative traits, like blood pressure and height (multifactorial)
• caused by additive effects of multiple genes, so these traits follow a normal bell curve distribution
• underlying genes involved are inherited in usual mendel fashion