MCD – Genetics 2 – Inheritance of Variation
Anil Chopra
1. Define a polymorphism
A Polymorphism is a variant present in the population at a frequency of MORE than
1%. i.e. the genes are variable amongst the organisms of that particular species.
This differs from a mutation which is a variant present in the population at a
frequency of LESS than 1%.
2. Describe variation in humans
If something is highly variable then it is also HIGHLY POLYMORPHIC. e.g. eye
colour.
3. Describe the inheritance of variation
Variation can occur at two main stages
 At metaphase I (of meiosis I) where the homologous pairs of chromosomes line
up along the equator of the cell. The combination of different chromosomes in the
different daughter haploid cells can lead to variation.
 At prophase I (of meiosis I) where recombination can occur.
4. Define genetic markers
Markers are “flags” in the genome which we are able to see and therefore follow the
inheritance of the genes that they are part of. They can be various things including:
- Genes
- Restriction fragment length polymorphisms (RFLP)
- Mini satellites (Large repeat sequences (500bp) Highly polymorphic, nonrandom, assayable, unstable)
- Micro satellites(Short sequence repeats (2-4bp) Highly polymorphic, random,
assayable, unstable)
- Single Nucleotide polymorphisms. (Single base changes e.g. C to T;
Polymorphic (2-3 alleles), random, assayable, unstable)
Ideally markers should be:
HIGHLY POLYMORPHIC
o Informative for many individuals
RANDOMLY DISTRIBUTED
o Not clustered at telomeres/centromeres
EASILY ASSAYABLE
o Simple technique, little time
o Automation
- STABLE
o No change through generations
5. Describe how markers are used to investigate variation.
6. Explain how markers are used to follow inheritance.
Markers are used following inheritance and variation.
A CentiMorgan is a measure of recombination. 1cM = 1% recombination. (i.e. one in
a hundred times, the two loci appear to have recombined) 1 cM is approximately the
equivalent of 1 megabase of DNA.
Linkage is association of any known marker with another marker more often than by
chance (>50%)
Genetic Linkage – association is heritable often because of…
Physical Linkage – markers are close together on chromosome
HOWEVER – genetic linkage can be caused by functional linkage.
This can be measured by the LOD score (Log of Odds Score)
 If LOD score = 3  indicative of linkage
 If LOD score = -2 NOT indicative of linkage.
7. Draw a pedigree
8. Describe recessive, dominant and X-linked inheritance
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AUTOSOMAL - Involving chromosomes 1-22, NOT X and Y
SEX-LINKED - Involving sex chromosomes, X and Y
RECESSIVE - Two defective gene copies required
DOMINANT - One defective gene copy required
An example of an autosomal dominant inheritance:
achondroplasia
• At least one diseased parent
• Transmitted by M or F
• Vertical transmission
• M or F affected
• 50% diseased
An example of an autosomal
recessive inheritance: cystic fibrosis
• No diseased parent
• Transmitted by M or F
• Usually no family history
• M or F affected
• 25% diseased
(50% inherit defective gene)
An example of a sex-linked recessive inheritance:
haemophilia
• No diseased parents
• M affected
• Transmitted by carrier F
• 50% sons diseased
• 50% daughters carriers
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An example of a sex-linked dominant inheritance: hypophosphatemic rickets
Diseased parent
M and F affected
If father affected then
o All daughters diseased
o No sons
If mother affected then
o 50% diseased sons
o 50% diseased daughters
9. Describe co-dominant inheritance
CO-DOMINANT - Both alleles are expressed (An example of this would be Blood
Groups