The inheritance of Human disease Flashcards
Revision
What is the definition of a syndrome?
A syndrome is a collection of abnormal physical features with single cause.
What are the differences and similarities between Non Mendelian Inheritance and Mendelian Inheritance?
Mendelian Inheritance - Autosomal dominant - Autosomal recessive - X-linked - (mitochondrial) Non Mendelian - Methylation/ Imprinting - Mitochondrial inheritance - Mosaicism Both involve multi-factorial inheritance.
What is Autosomal Recessive?
This is where you need 2 faulty copies of a gene to cause disease.
Often only one generation affected.
1 in 4 risk of an affected child if parents are carriers. increased likelihood in consanguineous families.
The chance of this occurring is far more likely if the parents share genes e.g. first cousins.
How do X linked recessive genes occur?
This is where a gene fault lies on the X chromosome
In terms of diease genes, the Y chromosome is almost irrelevant
On the X chromosome you have genes for
- Dystrophin
- Haemophilia
On the Y chromosome you get genes for
- SRy (male determination)
The Y chromosome has not many genes at all where as the X chromosome has lots of genes.
In X linked disease, if the mother is a carrier and the father is not, what are the possible outcomes for their offspring?
Normal Female
Carrier Female
Affected Male
Normal Male
In X-Linked Recessive Inheritance what is the difference in the outcome for offspring depending on which parent is the carrier?
A female carries a mutation but will not show major feautres of disease
For a female carrier
- Half of the male children of a carrier will be affected
- Half of the female children will be carriers
If an affected male has children
- All of the male children will be normal (no male to male transmission)
- All of female children will be carriers
What is Caveat?
This is where a female carrier may show mild features of an X-linked disease.
This is because half of all X chromosomes are deactivated in females and so roughly half on those that are still active could be affected an therefore the female could show mild features of an X-linked disease.
What exactly is X inactivation and what are the consequences of this is females?
In female cells only one X chromosome is active.
Female zygote - Random X inactivation - Person
In a female carrier half the cells have the working gene on average.
In Classical “Rare” genetic disorders how does the phenotype come about?
Phenotype = Genotype (a single mutation) + Environment
Mendelian Inheritance
Words that you need to know
Penetrance
Polymorphism
Mutation
If you don’t know them, look them up!!
All common diseases a combination of?
Disease = (lots of small genetic effects) + Environment
What is normal?
A You
B The commonest sequence
C Me
B
What are Single Nucleotide Polymorphisms (SNPs) and how often do they occur?
Alterations in DNA sequence
Every 100 to 300 bp
Over 10 million possible SNPs in total
Each given a unique id (rs number)
3,000,000 variations from “normal” in each person
Given that:
You are all (more or less) normal
You have genetically determined differences. Therefore, what effect do SNP’s have?
Therefore:
SNPs must exert effects that are not (in themselves) a disease
These effects will still be through gene function.
Some of these effects make you more prone to disease.
For each SNP what questions do you need to ask?
- Where it is
- What it is
- If it has an effect
- Population frequency
3 different genotypes possible at each snp for example: gg ga or aa
Most SNPs have no effect.
SNPs that do have an effect are expected to have smaller effects than a rare disease causing mutation.
However some polymorphisms can completely destroy a gene without causing disease.
