🐄 Allele Variation

Possibilities Outside of Mendel’s Crosses

• Genes can (and usually do) have more than 2 alleles

• Different alleles affect phenotype differently

• Additional factors at a single locus can affect phenotype

Genes Usually have 2+ Alleles

• Most common allele is called “wild type”

  • Designated with superscript + (e.g. A⁺ or c⁺)

• All other alleles are considered mutants (e.g. c^ch, c^h, c)

• Any allele found at appreciable frequencies (at least 1%) is considered to be a polymorphism/variant

• Note: Diploid organisms can only ever have 2 alleles in there genome at one time

• e.g. Each of four different alles of “c” gene in rabbits affects coat color differently

  • c⁺c⁺ -  Wild type (most common)

  • c^hc^h - Himalayan (h) 

  • c^chc^ch - Chinchilla (ch)

  • cc - No pigmentation

Gene Mutations

• Different mutations in a gene can cause the same disorder but different phenotypes

• Missense

  • One amino acid is replaced with another

  • Changes function of protein

• Nonsense

  • Results in premature stop codon

• Frameshift

  • Deletion

  • Insertion

What Makes an Allele Dominant/Recessive

• When only one good copy (e.g. R in Rr) of an allele is sufficient to make the protein required for the biological process to occur (e.g. make round seeds in Rr)

  • R would dominant

  • r would recessive

• Recessive mutations almost always involve mutation in gene that results in some loss of protein function:

  • DNA mutations would create recessive alleles (e.g. nonsense mutation leads to null recessive allele, missense mutation leads to hypomorphic recessive allele)

  • Null allele: Complete loss of function

  • Hypomorphic allele: Partial loss of function

    • Hypo = Beneath, Morphic = Morphology/phenotype

Types of Dominance

• Each version of a gene at a particular locus is defined as an allele

  • Not as simple as “dominant” or “recessive”

• Different types of dominance

  • Complete (AA phenotype = Aa phenotype ≠ aa phenotype)

  • Incomplete (Aa = black, Aa = grey, aa = white)

  • Codominance (AA = black, Aa = black with white spots, aa = white

Antennapedia (Antp) Mutation

• Dominant gain-of-function mutation

• Causes Antp gene to be expressed in wrong place (a regulatory mutation)

• Normally, Antp controls leg development in thorax, but in this mutation it is misexpressed in head, leading to legs growing where antennae should be

• Dominant: A single mutated allele is enough to cause the phenotype. (Aa)

• Gain of function: The gene is still active but in the wrong place or at the wrong time

• Regulatory mutation: The mutation affects when and where the gene is turned on, not the protein itself

Complete Dominance

• Heterozygous phenotype is same as homozygous dominant (AA = Black, Aa = Black)

Complete Dominant Mutations

• Phenotype of AA is same as Aa - Just one mutated allele (Aa) is enough to cause effect

  • Gain-of-Function mutation - Mutation adds new function (e.g. gene being expressed in wrong place, leg where antenna should be)

  • Loss-of-Function mutation - Mutation disrupts normal function of gene (e.g. stops protein from working, no antennas at all)

• Phenotype is wild type: aa leads to both antennae

Incomplete Dominance

• Neither A or a is dominant or recessive

• When alleles mix, their traits also mix (e.g. color)

  • Dominance of each trait is incomplete, not fully red or white

• AA = Red

• Aa = Pink

• aa = White

• Phenotype ratio is 1:2:1 (allele 1 : mix : allele 2)

  • Normal dominant/recessive phenotype ratio is 3:1 (dominant : recessive)

Codominance

• Heterozygous phenotype expresses traits form both AA and aa phenotypes

• e.g. BB = Black, WW = White, BW = Black with white spots

  • BW will sometimes be expressed as BB and sometimes as WW, leading to both being expressed in the entire coat/skin

Comparing Types of Dominance

Blood Types

• ABO blood group in humans has a multi-allelic system AND codominance

  • I^A is dominant over i

  • I^B is dominant over i

  • I^A and I^B are codominant

• Expressed using I

• Blood type (phenotype)

  • A - I^AI^A or I^Ai

  • B - I^BI^B or I^Bi

  • AB - I^AI^B

  • O - ii

• Antigens (think: same as phenotype name, identifies blood type)

  • A - A antigens

  • B - B antigens

  • AB - A and B antigens

  • O - no antigens

• Antibodies (think: fight off what they aren’t)

  • A - Anti-B

  • B - Anti-A

  • AB - None

  • O - Anti-A and Anti-B

• Compatibility

  • A can receive A and O, since it has anti-B antibodies (it will recognize the B antigens on the B and AB blood cells)

  • B can receive B and O, since it has anti-A antibodies (it will recognize the A antigens on A and AB blood cells)

  • AB can receive any, since it has no antibodies (it won’t detect antigens on A, B, or O cells)

  • O can receive only O, since it has anti-A AND anti-B antibodies (it will recognize A and B antigens on A, B, and AB cells)

Additional Factors at Single Locus Can Affect Phenotype

• Penetrance: Percentage of individuals having a particular genotype that express expected phenotype

  • Complete = 100% of individuals with genotype express phenotype

  • Incomplete < 100% of individuals with genotype actually express phenotype

  • e.g. Person has polydactyly allele but doesn't have extra fingers, trait has incomplete penetrance

• Expressivity: Degree to which character is expressed

  • Phenotype is present, but expression varies between individuals

  • e.g. One person with polydactyly allele has full extra finger, another person with the same apple only has a small extra finger

Incomplete Penetrance in Polydactyly

• Individuals do not express trait even though they have the appropriate genotype

• 100% penetrant trait = All affected have it

• Non-penetrant trait = None that are affected have it

Variable Expressivity

• Not all Individuals express a trait at the same level even though they have the same genotype

• Minor abnormality: Minor extra digit, non-functional

• Definite abnormality: Fully functional extra digit

Incomplete Penetrance and Variable Expressibility Causes

• Unclear, possibilities:

  • Environment (temperature during development, diet)

  • Epigenetics (changes in genotype of mutant offspring is less severe in older female parents expressions, but not due to mutations)

  • Maternal age (e.g. Icabod mutation. Older female fish = Milder phenotype)

Gene Expression May be Affected by Maternal Age

• Phenotype of mutant offspring is less severe in older female parents

Gene Expression May be Affected by Environmental Effects

• Temperature-sensitive allele: Allele whose product is functional only at certain temperature

• Image: Fruit fly has mutation in wing-development gene

  • At low temps, protein is non-functional

  • Protein is functional at warmer temps

  • This would be a cold-sensitive mutation (only mutates at cold temps, normal at warm temps)

• e.g. Expression of Himalayan allele in rabbits is temperature-dependent

• Rabbit in image was reared below 25 degrees C

• Its pigment is restricted to extremities where body temp falls below 25 degrees C and enzyme that produces pigment is functional

• This would be a heat-sensitive mutation (only mutates at warm temps, normal at cold temps)