Mendelian Inheritance of Human Disease

Question 1

what are different types of mutation that can affect a gene?

Answer 1

• base change causing amino acid change (missense)
• base change causing premature stop
• insertion or deletion of bases ‘in frame’
• insertion or deletion of bases out of frame
• mutations affecting promoters or splicing

Question 2

what are the types of disease-causing mendelian inheritance mutations?

Answer 2

• autosomal dominant
• autosomal recessive
• x-linked

Question 3

what are the effects of promoter and splice site sequence changes?

Answer 3

stop transcription or cause abnormal splicing

Question 4

what are the effects of a base change, causing an amino acid change?

Answer 4

• change in protein sequence
• not every base change causes disease
• may or may not reduce protein function
• some missense mutations make a protein work faster

Question 5

what can a base change result in?

Answer 5

• amino acid change

- premature stop codon

Question 6

what is a disorder with mendelian inheritance?

Answer 6

when a change in a single gene, sufficient to cause clinical disease, is inherited in a fashion predicted by Mendel’s laws

Question 7

what is non-Mendelian inheritance?

Answer 7

everything else including common ‘multifactorial’ diseases

Question 8

what are presentations of Marfan’s syndrome?

Answer 8

• pectus excavatum
• arachnodactyly
• dilation of aorta

Question 9

what causes Marfan’s syndrome?

Answer 9

mutation in fibrillin 1 (FBN1)

Question 10

what is locus heterogeneity?

Answer 10

same disease caused by mutations in one of several genes

Question 11

what are features of autosomal dominant inheritance?

Answer 11

• disease seen in all generations
• 50% risk of affected child if parent is affected
• disease severity variable (may not show disease)
• males and females equally affected

Question 12

what are features of autosomal recessive inheritance?

Answer 12

• often only one generation affected
• 1 in 4 risk of affected child if parents carriers
• increased likelihood in consanguineous families

Question 13

what are presentations of Duchenne Muscular Dystrophy?

Answer 13

• mild developmental delay
• slow to walk
• difficulty standing
• unable to run
• on examination: hypertrophy of calf muscles, proximal weakness

Question 14

what happens concerning female carriers and x-linked recessive inheritance?

Answer 14

• female carries a mutation but will not show major features of disease
• half of male children of carrier will be affected
• half of female children will be carriers

Question 15

what happens with x-linked recessive inheritance if an affected male has children?

Answer 15

• all of male children will be normal (no male to male transmission)
• all of female children will be carriers

Question 16

what is nonpenetrance?

Answer 16

failure of a genotype to manifest

Question 17

what is variable expression?

Answer 17

when different family members might show different features of a disorder

Question 18

what are features of mitochondrial inheritance?

Answer 18

• rare
• maternal transmission only
• sons/daughters equally affected