1. Genetic Linkage and Recombination
Mendel was lucky - the genes he chose all segregated independently
This is not true of all genes - many genes are linked
In humans, there are 23 pairs of chromosomes and about pairs of genes - each chromosome has a few hundred to a few thousand genes
Genes close together on the same chromosome are linked and do not segregate independently

2. Terms & Definitions
Genes can have several different forms due to mutations in the DNA. These forms are called alleles. Property of having different forms is called polymorphism
Organism with 2 copies of the same allele of a gene in diploid cells is homozygous for the gene
Organism with different alleles of a gene in diploid cells is heterozygous for the gene
Males are hemizygous for genes on X and Y chromosomes

3. Modes of inheritance
Dominant alleles affect the phenotype when present in 1 copy (heterozygous), e.g. Huntington’s disease
Recessive alleles affect the phenotype only when present in 2 copies (homozygous), e.g. cystic fibrosis
Can tell whether dominant or recessive by studying Mode of Inheritance in families (examples in my first lecture)

4. Oogenesis & spermatogenesis (animals)
Oogenesis is the process of egg formation
Spermatogenesis is the process of sperm formation
Both go through several stages, with (in mammals) different timing in males than females
Sperms go through more cell divisions than eggs do - more chance of mutation

5. Fertilisation
2 haploid cells (egg, sperm) form 1 diploid cell (the zygote) which develops into the embryo
Whether sperm contained an X or Y chromosome determines if embryo is female or male
Embryo contains an assortment of genes from each original parent - more genetic diversity
Mitochondria (and their DNA) come only from mother via the egg - maternal inheritance

6. Meiosis
Process of cell division in germ cells, to produce eggs or sperm (gametes)
1 diploid cell 2 haploid cells
Goes through several defined stages
Chromosomes are passed on as re-arranged copies due to recombination - creates genetic diversity

7. Meiosis and Recombination
Chromosomes pair up
DNA replication
Chiasmata form
Recombination
1st cell division
Gametes
2nd cell division
Result: meiosis generates new combinations of alleles

8. The overall process Mum Egg Development to adult Dad Sperm
Fertilisation
Meiosis
Recombination

9. How much genetic variation?
About 35,000 genes in humans
If each gene has only 2 alleles (probably an underestimate), then:
Number of possible genotypes = 335,000 = 1016,700
Far more than all the atoms in the Universe!
Essentially, we are all genetically unique (except identical twins)

10. Recombination
The closer together 2 genes are on the same chromosome, the less likely there is to be a recombination between them - such genes are linked and do not segregate independently
Genes that are far apart are likely to have a recombination between them and will segregate independently - such genes are unlinked
Genes on separate chromosomes are unlinked

11. Linkage to an autosomal dominant gene
A and a are alleles of a “marker”
gene AA Aa
Yellow shading indicates affected
with a genetic disease (NOT caused
by gene A/a) aa Aa
Allele a of the marker gene
always segregates with the disease,
so the 2 genes must be linked Aa aa Aa aa

12. An application of linkage
Can do prenatal diagnosis for genetic disease using a linked gene
Useful when you don’t know exactly what gene is causing the disease bb BB Bb ? bb