Pedigrees And Patterns Of Inheritance Flashcards
What is the difference between proband and consultand?
Proband = affected individual which makes the family come to the attention of the investigator
Consultand = Person presenting for genetic advice to find their risk factor of inheriting the disease
How are family pedigrees labelled?
Generations are specified by roman numerals from oldest generation down
Individuals in any generation are numbered 1,2,3 according to birth order in particular sibships
Dominance v recessiveness
Properties of characters not alleles
Character is dominant if present in heterozygote and recessive if not
Sickle Cell Anaemia:
- SCA is recessive - only seen in homo
- Sickling trait is dominant - seen in hetero
Semi dominant can be used for conditions where hetero has intermediate dominant
Males are hemizygous for loci on X and Y chromosome (only 1 copy of each)
What is codominance?
2 different alleles are expressed
As one isn’t dominant over the other, the phenotype is a mix of both
e.g. ABo Blood group (A and B)
What are the characteristics of Autosomal Dominant Inheritance?
Manifests in hetero state
Usually affects males and females equally
Transmitted by either sex to either sex
Wouldn’t expect to see offspring with disease if both parents are unaffected (unless arised through new mutation)
Offspring of affected parent have 1/2 chance
E.g. Myotonic Dystrophy, Huntington’s disease
What are the characteristics of Autosomal Recessive Inheritance?
Mutation must be present in homo state
Hetero are healthy but are carriers
Affects males and females equally
Affected people usually born to unaffected parents
Offspring of affected parent have 1/4 chance
Affected people usually in single sibship in one generation
E.g. Cystic Fibrosis
What is Genetic Heterogeneity?
The same or similar phenotype is caused by different genetic factors
Two types:
- Allelic: Different mutations in the same gene give rise to the same genetic condition
- Locus: Same clinical phenotype results from mutations at one or several different loci/genes
What are the characteristics of X-linked Recessive Inheritance?
Determined by gene on X, usually only males
Male with mutant X is hemizygous
Transmitted by hetero female carriers (XmXw)
1/2 males from carrier females affected
Affected males transmit to carrier daughters but not sons (sons inherit Y which is fine)
Affected male usually born to unaffected parent
E.g. Duchenne Muscular Dystrophy, Fragile X Syndrome, Haemophilia
What are the characteristics of X-linked Dominant Inheritance?
Both affected but females more common
Females usually less severe
Affected females transmit to sons/daughters
Affected males transmit to daughters only
Child of affected female has 1/2 chance
E.g. Vitamin D Resistant Rickets
What are the characteristics of Maternal (Mitochondrial) Inheritance?
Always inherited from mother but affects both males and females
Can have incomplete penetrance (multiple types of mito, different mutations or copies)
Other Considerations Of Patterns Of Inheritance?
Pleiotropy: Multiple effects of gene in different systems
Variable Expressivity: Variation in phenotype in different people
Penetrance: Proportion of hetero for dominant gene who express a trait
Why are Y-linked diseases so much rarer?
There are very few genes on the Y chromosome (200 compared to over 1400 one the X chromosome)
These diseases will only affect males and will be able to trace through family pedigree quite easily
Examples:
- Retinitis Pigmentosa (affect retina and lose vision over time)
- Swyer Syndrome (Failure of sex glands to develop but can affect girls too and be inherited in different ways)
What is Linkage Analysis?
Linkage describes cosegregation of genetic variants that are close to each other unless a recombination separates them
Linkage analysis isn’t used any longer in human genome mapping but has some utility in rare disease gene discovery and risk assessment
