Genetic linkage and gene mapping

Morgan (1900s)

First to associate a specific gene with a specific chromosome

- Nobel prize 1933

Drosophila

Small fruit fly used to study basic mechanisms of inheritance

Morgan's terminology

- normal phenotype: wild type (+)

- alternative trait to wild type: mutant phenotype

- gene takes its symbol from 1st mutant (e.g. eye colour: 1st mutant = white (w), wild type = red (w+)

Morgan's first cross

P- red eye (female) x white eye (male)

F1 results- all red eyes

F1 (red) x F1 (red)

F2 results - 3:1 (red:white)

First cross conclusions

- red (w+) dominant

- white (w) recessive

Morgan's second cross

F2 female (red) x F2 male (white)

F3 results: 1:1 (red:white)

Second cross conclusions

Female flies are heterozygous

Morgan's sex linkage hypothesis

- eye colour gene locus is on the X chromosome

- drosophila sex is determined by XY

- males are 'hemizygous' and possess only one allele -> on their X chromosome

Genetic linkage

Genes on any given chromosome are physically linked together on the same DNA molecule

- tend to be inherited together

- linked genes do not conform to Mendelian patterns

Dihybrid test cross

2 traits crossed at the same time

- crossing an unknown dominant genotype with a known recessive to find out its genotype

- proves independent assortment: 1:1:1:1

Dihybrid test cross involving body colour and wing size

Parent 1: homozygous recessive mutant, phenotype: black and vestigial wings, genotype: bb vgvg

Parent 2: heterozygous wild type, phenotype: grey and normal wings, genotype: b+b vg+vg

Dihybrid cross results

2300 offspring

grey/normal (parent) = 965

black/vestigial (parent) = 944

grey/vestigial (recombinant) = 206

black/normal (recombinant) = 185

Dihybrid cross conclusion

- disproportionate number of parental phenotypes

- alleles tend to be inherited together (linked on the same chromosome)

- smaller number of recombinant phenotypes present due to crossing over

Crossing over

Homologous proportions of 2 nonsister chromatids exchange places

- physically exchange DNA at chiasma

- tension results in DNA duplexes breaking and rejoining crosswise

- occurs during prophase of meiosis 1

- contain both maternal and paternal DNA

Recombinant frequency (RF)

The proportion (or percentage) of recombinant cells or individuals

RF conclusions

0%

Sturtevant

The first to realise that Morgans proposal could be used to map genes

- student of Morgan

Genetic mapping

Determining the location of genes on chromosomes

- first genetic map illustrated the sequence of genes along a chromosome and the relative distance between the genes

How did Sturtevant map genes?

Assumed an equal chance of crossing over along a length of chromosome

- if 2 genes are far apart they are more likely to cross over (high RF) -> units 1 & 10 = 10x chance

- if 2 genes are close together they are less likely to cross over (low RF) -> units 1 & 2 = 1x chance at crossing

Stutevant's first map

Analysis of transmission and recombination between 3 mutant traits in Drosophila (yellow body, white eye, miniature wing)

- performed dihybrid crosses, calculated the RFs between each pair of traits

- RFs taken as a measure of distance (one map unit = a centimorgan (cM), 1cM = 1% recombination between 2 genes)

Sturtevants results

1: RF between y (yellow body) and w (white eye) = 6%

2: RF between y and m (miniature wing) = 34%

3: RF between w and m = 40%