Genetics - Inheritance Flashcards
What are the four types of Medelian inheritance?
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
What is an autosomal dominant disease?
This means that the gene abnormality is located on a non-sex chromosome and a single copy of this mutation is enough to cause the disease
Which individuals are affected by autosomal dominant disease?
It affects both homozygous dominant and heterozygous individuals
There is no carrier state
What are the three other features of autosomal dominant disease?
It affects both males and females in equal numbers
It means that anybody affected will have an affected parent
If the parents do not show a disorder then no further generations will have the disorder either
List four examples of autosomal dominant disease
Achondroplasia
Huntingson’s
Von Willebrand disease
HNPCC
What is an autosomal recessive disease?
This means that the gene abnormality is located on a non-sex chromosome and two copies of this mutation are required to cause the disease
Which individuals are affected by autosomal recessive disease?
It affects those that are homozygous recessive
Those that are heterozygous are carriers and may be partially affected
What are the three other features of autosomal recessive disease?
It is expressed relatively rarely
It usually skips generations
It affects both males and females in equal numbers
List four examples of autosomal recessive disease
Cystic fibrosis
Sickle cell anaemia
Thalassaemia
Wilson’s disease
What is an X-linked dominant disease?
This means that the gene abnormality is present on a sex chromosome and only one copy of the mutation is enough to cause the disease
What is an X-linked recessive disease?
This means that the gene abnormality is present on a sex chromosome and two copies of the mutation are required to have the disease
Which individuals are affected by X-linked recessive disease (male, female)?
It will be expressed in a female who has two copies of the defective allele
It will be expressed in a male who has one copy of the defective allele
What are the five other features of X-linked recessive diseases?
It affects many more males than females (males only have one X so there’s a greater chance that it will affect them)
It is not passed from an affected male to son (this is because the man would have given his Y chromosome if it was a son, not the X)
It means that usually the mother of an affected male is unaffected herself
It means that all daughters of affected fathers will either be carriers or be affected themselves
It means that the daughters who are affected must have a father which is affected and a mother who is at least a carrier
What are the three mechanisms of non-medelian inheritance?
Mitochondrial inheritance
Trinucleotide repeat expansions
Genomic imprinting
What is mitochondrial disease?
It refers to a group of disorders that affect the mitochondria - as a small amount of double stranded DNA is present (mtDNA)
Describe the inheritance pattern observed in mitochrondrial diseases
The inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
What % of children will inherit mitochondrial disease if the father is affected?
0%
What % of children will inherit mitochondrial disease if the mother is affected?
100%
What are homoplasmy cells?
These cells contain identical mtDNA
What are heteroplasmy cells?
These cells contain a mixture of two populations of mtDNA
How does the severity of mitochondrial disease vary in a family?
Heteroplasmy
This is the presence of more than one mitochondrial DNA within a cell
This means that as an individual who has a mitochondrial disease may only have one affected mitochondrion in each of its cells, however when they produce offspring, the number of affected mitochondria can vary with more mitochondria being potentially affected
This can continue throughout several generations, where the number of affected mitochondria continue to increase
The more affected mitochondria, the more affected the individual is by the disease
What investigation is used to diagnose mitochondrial disease?
Muscle biopsy
What is the histological feature of mitochondrial disease on muscle biopsy?
Red, ragged fibres
What are trinucleotide repeat disorders?
They are genetic disorders caused by an abnormal number of repeats (expansions) of a repetitive sequence of three nucleotides
How do trinucleotide repeat disorders present? What is this phenomenon known as?
They lead to an earlier age of onset in successive generations
Anticipation
Name seven trinuclotide repeat disorders
Fragile X (CGG)
Huntington’s (CAG)
Myotonic dystrophy (CTG)
Friedreich’s ataxia (GAA)
Spinocerebellar ataxia
Spinobulbar muscular atrophy
Dentatorubral pallidoluysian atrophy
What is genomic imprinting?
This is when the phenotype depends on whether the gene abnormality occurs on a gene inherited from the mother or father
For example, if a mother is a carrier of an autosomal recessive disorder, they can still pass on the disorder to their offspring if they pass on two mutated copies of the chromosome
Describe the principle behind genomic imprinting
Individuals inherit two copies of their genes - one from their mother and one from their father
In most cases, both copies of each gene are active in cells
In other cases, only one of the two copies are active
The active copy depends on the parent of origin, with some genes being active when they are inherited from a person’s father and other being active when they are inherited from a person’s mother
Name a disease that shows genomic imprinting
Prader Willi syndrome
What are pedigree charts?
They are charts that show how a genetic trait is passed through several generations of a family
What are punnet squares?
They are used to predict the potential offspring phenotype of two individuals
How do we calculate the genotype frequency?
We divide the number of individuals that the genotype is present by the total number of individuals
How do we calculate the allele frequency?
We add up all the number of individuals who have that allele and multiply it by how many alleles that they have
We then divide this number by the total number of alleles
