5. Monogenic inheritance

Question 1

Multiple allelism

Answer 1

For many traits/diseases there are more than one mutant allele at the locus

Question 2

Genetic compound

Answer 2

An individual who has two mutant alleles at a locus (complex heterozygosity)

Question 3

Genetic heterogeneity

Answer 3

Many conditions have different genetic causes

Question 4

Difference between monogenic and complex (multifactorial) diseases

Answer 4

• Monogenic: large families, one disease causing gene/family, genes with high penetrance
• Multifactorial: small families, several disease causing genes/patient, genes with small penetrance

Question 5

Pedigree pattern of AD inheritance

Answer 5

Vertical

Question 6

AD inheritance: How many offspring affected?

Answer 6

50% on average

Question 7

AD inheritance: Age effect?

Answer 7

Paternal age effect for new mutations

Question 8

Which protein is mutated in Marfan syndrome (AD)?

Answer 8

Fibrillin protein

Question 9

Muation in familial hypercholesterolemia (AD)

Answer 9

Mutation of LDL receptor gene (19p13.2) -> Multiple allelism

Question 10

Cause of osteogenesis imperfecta (AD)

Answer 10

Collagen mutations

Question 11

AR inheritance: Disease expression

Answer 11

Only in homozygotes

Question 12

AR inheritance: Pedigree pattern

Answer 12

Horizontal

Question 13

AR inheritance: Severity

Answer 13

Diseases tend to be more severe than AD diseases

Question 14

Pathomechanism of albinism (AR)

Answer 14

Phenylalanine -> Tyrosine -> Melanin (this last step will not happen)

Question 15

Pathomechanism of PKU (AR)

Answer 15

Phenylalanine will not be converted to tyrosine by Phe hydroxylase

Question 16

Pathomechanism of Cretinism (AR)

Answer 16

Phenylalanine -> Tyrosine -> Thyroxine (won’t produce thyroxine)

Question 17

AR deafness cause

Answer 17

Mutations of connexion 26

Question 18

Percentage of absence of vas deferens in males with CF (AR)

Answer 18

95% -> Causes infertility

Question 19

Two examples of human oligogenic disorders and their mutation loci

Answer 19

• Bardet-Biedl syndrome: Primary locus- BBS6/BBS2, BBS2/BBS4, secondary same?!
• Cystic fibrosis: Primary- CFTR, secondary: CFM1

Question 20

Polycystic kidney disease mutations

Answer 20

Can be both AR and AD:

• AR: Mutation of fibrocystic (PKHD1)
• AD: Mutation of polycystin 1 or 2 (PKD1 or 2)

Question 21

What is Werner syndrome?

Answer 21

Disease with premature ageing caused by a helices mutation