5. Monogenic inheritance Flashcards
Multiple allelism
For many traits/diseases there are more than one mutant allele at the locus
Genetic compound
An individual who has two mutant alleles at a locus (complex heterozygosity)
Genetic heterogeneity
Many conditions have different genetic causes
Difference between monogenic and complex (multifactorial) diseases
- Monogenic: large families, one disease causing gene/family, genes with high penetrance
- Multifactorial: small families, several disease causing genes/patient, genes with small penetrance
Pedigree pattern of AD inheritance
Vertical
AD inheritance: How many offspring affected?
50% on average
AD inheritance: Age effect?
Paternal age effect for new mutations
Which protein is mutated in Marfan syndrome (AD)?
Fibrillin protein
Muation in familial hypercholesterolemia (AD)
Mutation of LDL receptor gene (19p13.2) -> Multiple allelism
Cause of osteogenesis imperfecta (AD)
Collagen mutations
AR inheritance: Disease expression
Only in homozygotes
AR inheritance: Pedigree pattern
Horizontal
AR inheritance: Severity
Diseases tend to be more severe than AD diseases
Pathomechanism of albinism (AR)
Phenylalanine -> Tyrosine -> Melanin (this last step will not happen)
Pathomechanism of PKU (AR)
Phenylalanine will not be converted to tyrosine by Phe hydroxylase
Pathomechanism of Cretinism (AR)
Phenylalanine -> Tyrosine -> Thyroxine (won’t produce thyroxine)
AR deafness cause
Mutations of connexion 26
Percentage of absence of vas deferens in males with CF (AR)
95% -> Causes infertility
Two examples of human oligogenic disorders and their mutation loci
- Bardet-Biedl syndrome: Primary locus- BBS6/BBS2, BBS2/BBS4, secondary same?!
- Cystic fibrosis: Primary- CFTR, secondary: CFM1
Polycystic kidney disease mutations
Can be both AR and AD:
- AR: Mutation of fibrocystic (PKHD1)
- AD: Mutation of polycystin 1 or 2 (PKD1 or 2)
What is Werner syndrome?
Disease with premature ageing caused by a helices mutation
