Genetic Linkage and Recombination

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 35000 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.
  Huntingtons 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
2nd cell division
Gametes
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 dont know exactly what gene is
  causing the disease

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