Typical and Atypical Mendelian Inheritance Flashcards
What are the 4 types of typical Mendelian inheritance?
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
What are the 4 types of atypical Mendelian inheritance?
Genetic anticipation
Pseudo-dominant inheritance
Mitochondrial inheritance
Pseudo-autosomal inheritance
Give 4 examples of autosomal dominant disorders.
Achondroplasia
Hereditary breast/colon cancer
Autosomal dominant polycystic kidney disease (ADPKD)
Neurofibromatosis type 1 (NF1)
List 3 features of autosomal dominant inheritance on family trees.
Vertical transmission pattern (i.e. every generation is affected)
Males and females equally affected
Father-son transmission
What is variable expression?
What causes it?
Give 1 example of this.
AD conditions in which individuals within the same family can be affected to different extents
CAUSED BY: modifier genes
EXAMPLE: FGFR2 gene in BRCA2 mutations
How do you tell the difference between autosomal and X-linked dominant disorders?
The two can look very similar.
Father-son transmission
Autosomal: present
X-linked: not possible, because fathers pass on Y chromosome to sons
List 4 other features of autosomal dominant disorders.
Give a brief description of each.
Variable expression
- Caused by modifier genes
- Individuals within the same family can be affected to different extents
Incomplete penetrance
- Caused by modifier genes
- Individuals who are unaffected due to incomplete penetrance can still pass on the mutation and have affected children
Complete penetrance
- Mutation will definitely cause disease
- E.g. achondroplasia
Gonadal mosaicism
- Caused by new mutations in some egg/sperm cells in unaffected individuals
- These (unaffected) parents will have a slightly higher risk of having affected children
Give 5 examples of autosomal recessive disorders.
Sickle cell anaemia Cystic fibrosis Phenylketonuria (PKU) Spinal muscular atrophy (SMA) Congenital adrenal hyperplasia (CAH)
List 3 features of autosomal recessive disorders on family trees.
Horizontal patterns (i.e. affected individuals within same generation)
Males and females affected equally
Consanguinity
List 3 other features associated with autosomal recessive disorders.
Give a brief description of each.
Carriers
-Heterozygous individuals carrying one affected gene, which isn’t enough to cause disease
Compound heterozygotes
-There are 2 mutated alleles, but each allele contains a different mutation
Complete penetrance
-If the mutations are present, the individual will always have the disease
Give 2 examples of X-linked recessive disorders.
Duchenne muscular dystrophy (DMD)
Becker’s muscular dystrophy (BMD)
List 4 features of X-linked recessive disorders on family trees.
Knights move pattern (affected males and affected uncles)
No male-male inheritance
Mostly (or only) males affected
Manifesting carriers
What are manifesting carriers?
What is the cause of this?
Female carriers who present with an X-linked recessive disorder, despite only having 1 mutated X chromosome.
Caused by: skewed X inactivation (i.e. too many health X chromosomes are inactivated)
List 3 examples of X-linked dominant disorders.
Which of these are always fatal for males?
Vitamin D resistant rickets
Incontinentia pigmenti (male lethality)
Rett syndrome (male lethality)
List 3 features of X-linked dominant disorders on family trees.
Vertical pattern
Mostly females affected
No male-male transmission
Give 3 examples of disorders showing genetic anticipation.
Huntington’s disease
Fragile X syndrome
Myotonic dystrophy
Give 1 example of a disorder with pseudo-dominant inheritance.
What is the carrier frequency for this disorder?
Gilbert’s syndrome (carrier frequency 50-60%)
Give 1 example of mitochondrial inheritance.
Leigh syndrome
List 2 features of disorders with mitochondrial inheritance.
Variable expression
Only inherited from mother (because egg cell passes on mitochondria, sperm cell does not)
Define “pseudo-autosomal inheritance”.
X-linked inheritance which appears as an autosomal dominant condition, due to the fact that the mutation is found on a region of the X chromosome that is commonly joined onto the Y chromosome (a pseudo-autosomal region, PAR1 or PAR2)
Give 1 example of a disorder caused by pseudo-autosomal inheritance.
Leri-Weill dyschondrosteosis
Describe the pathophysiology of pseudo-autosomal inheritance. (2)
- The PAR1 and PAR2 regions of the X chromosome frequently attach to the Y chromosome (i.e. undergo recombination)
- This is NORMAL - When there is a mutation in PAR1 or PAR2, this mutation will be inherited in a way that appears autosomal, due to the fact that it is on both the X and Y chromosome