Genetics in Clinical Practice Flashcards
(24 cards)
Definition of mutation
Pathogenic alteration in the gene affecting the structure or function of a protein
Definition of hemizygous
Presence of only 1 copy of chromosome or gene (X chromosome in males)
Definition of phenotypic heterogeneity
Many phenotypes arise from 1 variant
Definition of genetic heterogeneity
Many variants => 1 phenotype
Definition of variable (reduced) penetrance
Proportion of carriers who show within and between families
Definition of variable expression
Extent of clinical manifestation can vary within and between families
Definition of germline mosaicism
Parent carries a small proportion of gametes that harbour the same mutation
Definition of compound heterozygosity
Different mutant recessive alleles in same gene at same locus => disease
What are Mendel’s 2 laws of inheritance
Law of segregation
-everyone has 2 alleles of each characteristic but only 1 is passed on
Law of independent assortment
- genes at different loci segregate independently
- does not apply if 2 loci are closely linked
What are the 3 main types of Mendelian disorder
Autosomal dominant
Autosomal recessive
Sex linked
MUTATION IS IN 1 GENE
Describe
- phenotypic heterogeneity
- genetic heterogeneity
Phenotypic heterogeneity
-many phenotypes arise from 1 variant
Genetic heterogeneity
-many variants => 1 phenotype
Describe the pedigree symbols for
- male and female
- marriage (consanguinous, many, unrelated)
- deceased
- affected with disorder/carrier
- couple with children/pregnant with unknown gender
🔲🔘 🔲-🔘 🔲=🔘 🔲/🔘-🔲 🔲with a line through it ⬛️ ⏺ child has P in🔷
What are the 2 types of phenotypic expression possible in autosomal dominant conditions
Variable (reduced) penetrance
- proportion of carriers who show phenotypic signs of condition
- Not all individuals who inherit a dominant mutation express it
Variable expression
-extent of clinical manifestation can vary within and between families
Describe the 2 ways in which autosomal dominant conditions can arise
How can you test for one of these methods
Can be inherited or de novo
Parent carries a small proportion of gametes that harbour the same mutation => inherited
What are the risks associated with cosanguinity
Increased risk of recessive diseases in offspring
Probability of an unaffected child being a carrier => 2 in 3 (not limited to consanguinity)
Describe compound heterozygosity
Different mutant recessive alleles in same gene at same locus => disease
Describe how X inactivation affects the expression of X linked dominant and recessive disorders
Non random inactivation leading to chance expression in certain tissues
Affected females show mosaic pattern of involvement
What is involved in the 2 branches of a genetic diagnosis
- clinical
- genetic tests
Clinical
-clinical dysmorphic features
Genetic tests
- chromosome analysis
- FISH
- Array CGH
- Single gene testing
- NGS
- Methylation analysis
What is the function of a genetic diagnosis
Confirms diagnosis
Decreases need for other tests
Aids prognostication and recurrence risk, not predicitve
Reproductive choices/prenatal diagnosis
What is the function of single gene testing
For diagnosis/confirmation of genetic disorders
- prenatal diagnosis
- preimplantation genetic diagnosis
- carrier/presymptomatic at risk relatives
What are the 2 equations used in the Hardy Weinburg Principle
Allele frequencies p+q=1
Genotype frequencies p^2 + 2pq + q^2 =1
How would you calculate the risk of expressing an autosomal dominant phenotype in a child
Probability of inheriting mutant allele x penetrance
How would you calculate the risk of having a child affected by an X linked recessive disease
Carrier risk of mother x probability risk of passing on gene (0.5) x gender of child
How would you calculate the risk of passing on an autosomal recessive disease
Carrier risk in 1 parent x carrier risk in unaffected other parent x probability of offspring being homozygous recessive
