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

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

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)

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

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

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

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

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

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)

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

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

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