Inheritance Patterns Flashcards
Categories of Genetic Disorders
• Chromosome abnormalities
• Single gene disorders
• Multi-factorial and polygenic disorders e.g. spina bifida, cleft lip and palate
Mendel Deduced the Underlying Principles of Genetics
- Segregation
- Dominance
- Independent assortment
Dominance
Every gene has 2 alleles that code for a trait
In heterozygotes, one allele is dominant meaning it will always show, one is recessive and is masked by the dominant allele
Segregation
Allele pairs separate/segregate randomly from each other during meiosis – each cell has a single allele for each trait
Independent Assortment
Traits are transmitted to offspring independently of one another
Mendelian Inheritance
• Autosomal and sex-linked
• Dominant and recessive
Non-Mendelian Inheritance
• Imprinting
• Mitochondrial inheritance
• Multifactorial
• (Mosaicism)
Autosome
Any chromosome, other than the sex chromosomes (X or Y), that occurs in pairs in diploid cells
Recessive
Manifest only in homozygotes
Allele
One or more alternative forms of a gene at a given location (locus)
normal allele is also referred to as wild type
disease allele carries the pathogenic mutation
Homozygous
Presence of identical alleles at a given locus
homozygotes are affected
Heterozygous
Presence of two different alleles at a given locus
Heterozygotes are unaffected and are usually referred to as carriers
Allelic heterogeneity
The situation where different mutations within the same gene result in the same clinical condition e.g. cystic fibrosis.
Thus an individual with an autosomal recessive condition may be a compound heterozygote for two different mutations
In autosomal recessive inheritance the disease manifest in the homozygous state I.e “double-dose” of affected alleles.
Typical features include
Male and females affected in equal proportions
Affected individuals only in a single generation
Parents can be related, i.e. consanguineous
Consanguinity
Reproductive union between two relatives.
Autozygosity
Homozygosity by descent, i.e. inheritance of the same altered allele through two branches of the same family.
Summary (ARI)
Double-dose of same altered gene required to cause problems
· Carrier parents have no health problems themselves, but have 1 in 4 offspring risk
· Healthy siblings have a 2 in 3 chance of being carriers themselves
· AR conditions can affect any family, but more common in consanguineous unions
· Some AR conditions are more common in certain ethnic groups
Autosomal Dominant Inheritance
Disease manifest in the heterozygous state, i.e. only one affected gene needed
Typical features include
Male and females affected in equal proportions
Affected individuals in multiple generations
Transmission by individuals of both sexes, to both sexes
sometimes both parents are unaffected, this can be for three reasons: most commonly they don’t have the genes for it, gonadal mosaicism or SOMETIMES the mother has REDUCED PENETRANCE or VARIABLE EXPRESSION i.e. disease is there but not expressed clearly.
Only one defective gene needed. 50% chance of offspring having condition (1 affected and 1 unaffected parent). Example. Huntington’s disease. ONLY WAY TO PASS ON DISEASE FROM MALE TO MALE. Thus if you see male-male transmission, MUST BE AUTOSOMAL DOMINANCE INHERITANCE
Penetrance & variability
Penetrance
The percentage of individuals with a specific genotype showing the expected phenotype
• Complete: gene or genes for the trait are expressed in all the population
• Incomplete: the genetic trait is only expressed in parts of the population
Expressivity
Refers to the range of phenotypes expressed by a specific genotype
I.e will the disease be expressed more harshly in certain people, will the disease affect at a certain age
Recurrence risk
50% for transmission of mutation
BUT will the person be affected?
Depends on penetrance and expression
New mutation
Example – Neurofibromatosis type 1, up to 50% of cases occur as result of de novo mutation
Anticipation
Whereby genetic disorder affects successive generations earlier or more severely, usually due to expansion of unstable triplet repeat sequences
Example – Myotonic Dystrophy
Somatic Mosaicism
Genetic fault present in only some tissues in body.
