Non-Mendelian inheritance

When the heterozygote looks different

In Mendel's peas, a heterozygote looks exactly like the dominant homozygote. Many genes don't behave that way.

In incomplete dominance, the heterozygote has an intermediate phenotype. Cross red snapdragons (CᴿCᴿ) with white ones (CᵂCᵂ) and you get pink offspring (CᴿCᵂ). One copy of the red allele makes only about half as much pigment, which isn't enough for full red.

In codominance, the heterozygote shows both alleles fully and separately. In the MN blood group, a person with genotype LᴹLᴺ carries both the M and the N molecule on their red blood cells, side by side. Nothing is intermediate; both products are simply there.

Multiple alleles: the ABO blood groups

Any one person carries at most two alleles of a gene, but a population can hold many. A gene with more than two alleles in the population has multiple alleles.

The ABO blood group gene has three common alleles. Iᴬ makes an enzyme that adds one kind of sugar to a molecule on red blood cells, making the A antigen; Iᴮ adds a different sugar, making the B antigen, and i makes no working enzyme. Iᴬ and Iᴮ are codominant with each other, and both are dominant over i.

• Type A: IᴬIᴬ or Iᴬi.
• Type B: IᴮIᴮ or Iᴮi.
• Type AB: IᴬIᴮ, both antigens present (codominance).
• Type O: ii, neither antigen.

Alleles can also form a dominance series. Rabbit coat colour has four alleles: full colour is dominant over chinchilla, chinchilla is incompletely dominant over Himalayan, and Himalayan is dominant over albino.

Many genes, one trait: polygenic inheritance

Human height and skin colour don't fall into a few neat classes. They vary smoothly, in continuous variation, because they are polygenic: many genes each add a small amount, and the environment adds more.

Here's a simplified model. Suppose three genes each have a "+" allele that adds one unit of pigment and a "−" allele that adds none. A person heterozygous for all three can pass on anywhere from 0 to 3 "+" alleles, so a child of two such parents can have 0 to 6. Crossing two such triple heterozygotes gives seven classes in the proportions 1 : 6 : 15 : 20 : 15 : 6 : 1, already close to a bell curve. With more genes and some environmental effect, the steps smooth out completely.

Genes on the X chromosome

In humans and fruit flies, females are XX and males are XY. The Y is small and carries few genes, so for most X-linked genes a male has just one copy. He is hemizygous: whatever allele is on his single X shows up in his phenotype, dominant or recessive.

Thomas Hunt Morgan gave the classic demonstration. In 1910 he found a single white-eyed male among his red-eyed fruit flies. Crossed with red-eyed females, it gave all red-eyed offspring. But in the next generation the white eyes came back only in males. Morgan concluded that the eye-colour gene sits on the X chromosome.

Because of hemizygosity, reciprocal crosses (swapping which parent has which trait) give different results for X-linked genes, which doesn't happen for ordinary autosomal genes. A son always gets his X from his mother; a father passes his X to every daughter and to no son.

Clues that a pedigree shows an X-linked recessive trait, such as red–green colour blindness or haemophilia:

• Many more affected males than females.
• Affected males usually have unaffected parents; the allele came from a carrier mother.
• It is never passed from father to son.
• An affected female normally has an affected father (and a mother who is at least a carrier).

An X-linked dominant trait looks different: an affected father passes it to all of his daughters and none of his sons, and affected females outnumber affected males.

Inheritance outside the nucleus

Mitochondria, and chloroplasts in plants, carry their own small DNA. An egg contributes a whole cell's worth of cytoplasm, organelles included, while a sperm contributes essentially none. So these genes usually show maternal inheritance: all the children of an affected mother can inherit the trait, and an affected father doesn't pass it on. Correns's white four o'clock leaves followed exactly this pattern, through the chloroplasts.

A cell holds many copies of mitochondrial DNA, and they aren't always the same. Having a mix of normal and mutant copies is called heteroplasmy. A mitochondrial disease usually appears only once the mutant share passes a threshold, and the share can shift a lot when eggs are made. That's why siblings with the same mother can be affected very differently.

Same genotype, different phenotype

A genotype isn't a fixed recipe. The phenotype it produces can depend on the environment. Siamese cats carry a heat-sensitive version of tyrosinase, an enzyme that makes the pigment melanin. It only works in cooler skin, below about 33 °C, so the ears, face, paws and tail are dark while the warm body stays pale. Kittens are born almost white, since it's warm in the womb.

Hydrangea flowers are another example: the same plant tends to bloom blue in acidic soil and pink in alkaline soil. The pigment changes colour when it binds aluminium ions, which the roots take up more easily from acidic soil.

Even when the environment is the same, people with the same disease allele may differ. Penetrance is the fraction of people with a genotype who show the phenotype at all. Expressivity is how strongly it shows in those who do.

More exceptions worth knowing

• Pleiotropy: one gene affects several traits. The CFTR gene behind cystic fibrosis affects the lungs, the pancreas and sweat.
• Genomic imprinting: some genes are switched on or off depending on which parent they came from, marked by DNA methylation. IGF2, a growth gene, is normally used only from the father's copy. Losing the same region of chromosome 15 causes Prader–Willi syndrome if the father's copy is lost, but Angelman syndrome if the mother's copy is lost.
• Sex-limited traits appear in only one sex, even though both carry the genes, such as milk production in cattle. Sex-influenced traits are dominant in one sex and recessive in the other; pattern baldness is the classic textbook example, though its real genetics is more complex.

Key terms

Incomplete dominance

The heterozygote has an intermediate phenotype, such as pink snapdragons.

Codominance

Both alleles are fully and separately expressed in the heterozygote, such as blood type AB.

Multiple alleles

More than two alleles of a gene exist in a population, such as Iᴬ, Iᴮ and i.

Polygenic trait

A trait shaped by many genes with small additive effects, giving continuous variation.

Hemizygous

Having only one copy of a gene, as males do for most X-linked genes.

Maternal (mitochondrial) inheritance

Inheritance of organelle genes through the egg's cytoplasm, from the mother only.

Heteroplasmy

A mix of normal and mutant mitochondrial DNA copies in a cell or person.

Penetrance / expressivity

The fraction of carriers of a genotype who show the phenotype / how strongly it shows.

Genomic imprinting

Expression of a gene depends on which parent it was inherited from.

Check yourself

Try answering in your head before you open each answer.

• 1.A child has blood type O. The mother is type A and a man who might be the father is type AB. Could he be the father? Explain with genotypes.Show answerHide

  No. A type O child is ii, so each parent must have passed on an i allele. A type AB man is IᴬIᴮ and has no i to give. (The mother must be Iᴬi.)

• 2.In a pedigree, a rare trait appears in every child of an affected woman, both sons and daughters, but never in the children of affected men. Which inheritance pattern fits best, and why would X-linked dominant not fit?Show answerHide

  Mitochondrial (maternal) inheritance: every child gets the mother's mitochondria and essentially none of the father's. An X-linked dominant trait would pass from an affected father to all of his daughters, which isn't seen here.

• 3.A Siamese cat has a patch of fur on its back shaved and kept cold with an ice pack while it regrows. What colour will the new fur be, and has the cat's genotype changed?Show answerHide

  The new fur will grow in dark, because the heat-sensitive tyrosinase works in the cooled skin. The genotype hasn't changed at all; only the environment of those cells has, and the phenotype depends on both.