Application of Genetic Principles Flashcards
Describe the features of autosomal dominant inheritance [6]
- equal frequency and severity in males and females
- vertical pedigree pattern
- disease expressed in heterozygotes
- offspring of affected individuals usually have a 50:50 risk
- variable expressivity
- may be incomplete penetrance
What is penetrance? [2]
- the probability of a gene being inherited
- in some cases, despite the presence of a dominant allele, a phenotype may not be present (incomplete penetrance)
What is expressivity? [2]
- the variation in phenotypic expression when an allele is penetrant
- i.e. there can be a range of signs and symptoms that can occur in different people with the same condition (e.g. BrCa1 mutation can cause breast or ovarian cancer)
What are modifier genetic variants and give an example [2]
- affect the penetrance and expressivity by modifying the genotype and hence affecting the severity of the disease
- e.g. FGFR2 variants in BrCa2 mutation carriers
Give examples of conditions that are inherited in an autosomal dominant fashion [5]
- achondroplasia
- inherited breast cancer
- Lynch syndrome (colon cancer)
- adult polycystic kidney disease (APKD)
- neurofibromatosis type 1 (NF1)
Describe the features of autosomal recessive inheritance [6]
- equal frequency and severity in males and females
- horizontal pedigree pattern
- disease expressed in homozygotes (2 identical mutated alleles) or compound heterozygotes (fault in same chromosome but 2 different genes)
- offspring of affected individuals have a low risk
- expressivity more constant within a family
- importance of consanguinity
What is pseudodominant inheritance? [1]
autosomal recessive condition appearing like AD due to high carrier frequency or consanguinity
Give examples of conditions that are inherited in an autosomal recessive fashion [5]
- cystic fibrosis (CF)
- phenylketonuria (PKU)
- sickle cell anaemia
- spinal muscular atrophy (SMA)
- congenital adrenal hyperplasia (hypoplasia is x-linked)
Describe the features of X-linked recessive inheritance [5]
- no male-to-male transmission
- knight’s move pattern
- mostly/only males are affected
- females can occassionally be affected due to skewed X-inactivation = these females are called manifesting carriers
- if the mother has the mutation in x-linked recessive condition:
- 50% of daughters are carriers
- 50% of sons are affected
- if the father has the mutation in x-linked recessive condition:
- none of the sons are affected
- all of the daughters are carriers
Give examples of conditions that are inherited in a X-linked recessive fashion [2]
- muscular dystrophy
- congenital adrenal hypoplasia
Describe the features of X-linked dominant inheritance [5]
- no male-to-male transmission
- vertical pattern
- if the mother has the mutation:
- 50% of daughters are affected
- if the father has the mutation:
- all daughters are affected
- females:males = 2:1
Genetic Anticipation:
- what is it? [1]
- what is it caused by? [1]
- example conditions? [3]
- refers to the increasing severity and decreasing age of onset of certain conditions in successive generations
- may result from the increasing size of the tract of trinucleotide repeats, which may lie outside the coding sequence
- example conditions:
- Huntington Disease
- Fragile X syndrome
- Myotonic dystrophy
Describe the genome in a mitochondria and from whom is it inherited from? [3]
- much smaller → only 37 genes
- circular chromosomes with no introns
- inherited only from mother, with all children inheriting to variable extents
What is heteroplasmy and what does it result in? [2]
- heteroplasmy is the tendency for a mitochondrial mutation to be present in only a proportion of the cell’s mitochondrial genome copies
- which results in variable severity of mitochondrial diseases between siblings
What is gonadal mosaicism? [1]
mutation might be in more than one egg or sperm cell in the parent’s gonads
