Lethal alleles

What is a lethal allele?

• Lethal alleles occur when a mutation results in an allele that produces a non-functional version of an essential protein.

• If an individual inherits a lethal combination of mutated alleles, it will die before or shortly after birth.

Huntington’s chorea

• http://www.youtube.com/watch?v=PCVO9c9q4tE

• http://www.youtube.com/watch?v=MRZoM5L5dak

Pedigree chart for Huntington’s disease

Genetic cross for Huntington’s

Abnormal ratios in genetic crosses• It is probably true that in genetic studies more

has been learned from abnormal ratios than that of normal ones.

Consider, for example, the inheritance of fur colour in mice.

• In mice, the allele for yellow fur (Y) is dominant to the allele for grey fur (y)• What ratios would you expect if a

pair of heterozygous yellow mice are mated?

• We naturally expect three quarters of the mice to be yellow and a quarter to be grey.• However, this is not the result we

actually observe when this genetic cross is carried out.• The observed results are 2/3 of the

offspring are yellow and 1/3 are grey.

So what is going on?• A possible explanation is that mice that are

homozygous for the yellow allele (YY) die before birth.

Or as a punnet square Yy

Y y

Y YY Yy dead yellow alive Yy y Yy yy yellow grey alive alive

What is the evidence for this?

• Crossing yellow never produces exclusively yellow offspring: a ratio of two yellow to one grey always results. This means all viable yellow mice are heterozygous and a living homozygous yellow mouse is an impossibility.

• Examination of the uteri of yellow female mice which have mated with yellow males usually reveals one of more dead embryos.

Is this allele dominant or recessive?

• It depends how we look at it.• The allele controlling fur colour is dominant,

but as a lethal allele it is recessive, exerting its effects only when in the homozygous state.

Lethal alleles in fruit flies, Drosophila melanogaster

In Drosophila fruit flies, a mutated allele which is dominant (C ) produces curly wings rather than normal wings (c )

• Fruit flies that are homozygous for curly wings do not survive.

• The expected 3 curly :1 normal ratio of flies does not occur

• However 2 curly: 1 normal does occur.• The homozygous dominant flies do not survive.• Draw a punnet square to show this.

Manx Cats

• Cats with tails have the genotype tt – but the tail-producing gene has a dominant mutation.

• In heterozygous cats, Tt the allele results in the tail-less Manx phenotype.

• However, when the homozygous dominant occurs, the alleles cause problems with spinal development, which are lethal.

• Draw a punnet square to show how the expected 3:1 ratio actually produces a 2:1 ratio.

Snapdragon plants and chlorophyll• Snapdragon plants can carry a dominant allele (G)

that causes plants to be unable to make chlorophyll.

• Chlorophyll is essential for photosynthesis and therefore survival, so plants that inherit two copies of the dominant allele die soon after germination.

• The heterozygous offspring have golden leaves

Draw a punnet square to show this.

Creeper allele in chickens

The Creeper allele

• The dominant creeper allele (C ) in chickens causes the legs to be shortened and stunted.

• If two creeper chickens are mated you would expect to ¾ offspring to be creeper and ¼ to be normal.

• Instead the ratio obtained is 2/3 creeper and 1/3 normal.

• Homozygous creeper chickens die before hatching.• Draw a punnet square to show this.