Chapter 12 problems are posted online

1, 4, 5, 9, 12, 14, 19, 25, 27a, 29, 32

Gene interactions

• Sometimes two genes interact to produce novel phenotypes:
• • Comb type in chickens
  • R-P- = walnut; R-pp: rose; rrPP=pea; rrpp=single
• A similar pattern is seen in colors of bell peppers
• • 9:3:3:1 R:Y:Br:G
• These crosses fit standard Mendelian two-locus expectations (9:3:3:1), but instead of combinations of two characters, they produce four types of a single character

Lethal Alleles

Sometimes one genotypic class is missing, so you can get 2/3: 1/3 ratios

Lethal alleles are commonly recessive.

Example from book: Yellow mice

• Yellow is an allele at the agouti locus
• Cross yellow x yellow
• Observe 2:1 yellow vs black
• Why? Yellow homozygotes die

This is an example of Pleiotropy (One gene has two phenotypes: color and survival)

Is it dominant for color?

Is it dominant for survival?

Gene environment interactions

• Temperature sensitive genes
• • Himalayan rabbits and Siamese cats have light-colored bodies with dark fur on their paws, nose, ears, and tail
  • All cells of these animals carry the same genes for pigment production, but the environment determines phenotypic pattern of expression
• Male pattern baldness
• • In this case, the genetic background is the "environment".
  • Dominant in males, recessive in females
  • how can you tell from the pedigree that it is not X linked?
• PKU and other nutritional mutants
• • No effect of gene if diet is controlled

Variation in Gene Expression

Expressivity means that the expression is variable

• Lobe eyes in Drosophila may be pronounced or weak
• Heterozygotes for lobe eyes in Drosophila show variable expressivity.
• All have the same genotype, but different expression of the trait.

Incomplete Penetrance means the trait is not expressed in 100% of the individuals

• BRCA1 is well known gene for breast cancer, but inheriting the gene does not mean you will necessarily get cancer. That cancer gene has low penetrance.
• Polydactyly (extra digits) is a dominant gene in humans, with only 70-80% penetrance. Occasionally, two normal parents can have an affected child. Since it is dominant one of the parents must have had the allele, but was not affected.

Complementation tests

You find two rare white flowers in different populations. Are they two mutant alleles at the same locus, or are they from different loci?

• Cross white x white
• What do you predict if they are:
• Mutations in the same gene?
• Mutations at different genes?

Why won't this work with dominant mutants?

Linkage

Everything we have done to this point assumes that different genes assort independently.

However, if genes are close together on a chromosome they will usually be inherited as a unit.

The first example of linkage came from Bateson and Punnett (testing Mendel's experiments on flower color and pollen size in peas) but they could not explain the anomaly.

T. H. Morgan was the first to suggest that linkage was because genes were close together on the same chromosome

Morgan's data

Purple-eye vestigal wing x red-eye normal wing (p/p v/v crossed with +/+ +/+)

The F1 is heterozygous at both loci p/+ v/+

Then backcross the F1 to the recessive (ppvv) parent

• What do you expect from this cross?
• Draw the punnet square using the possible gametes from the two parents to get the predicted F2 phenotypes.
• Morgan's data don't fit very well . . .
• • Phenotype number
  • pr+ vg+ 1339
  • pr+ vg 151
  • pr vg+ 154
  • pr vg 1195
  • X²=1764.8

General Pattens of Recombination

Recombination is a result of crossing over during meiosis

(When in meiosis does it happen?)

Crossing over is random (occurs on any part of the chromosome with equal probability)

Recombination is more likely when genes are far apart on a chromosome

Therefore, use the recombination frequency to estimate distances between genes

Constructing a map from Morgan's data

Purple-eye vestigal wing x red-eye normal wing

• Phenotype number expected
• pr+ vg+ 1339 708
• pr+ vg 151 708
• pr vg+ 154 708
• pr vg 1195 708
• X²=1764.8

Which are the recombinants?

If genes are linked and inherited as a unit, then most of the gametes will be the parental (non-recombinant) type. In this case, the two middle (single mutant) phenotypes are the recombinants.

What fraction of the flies are recombinants?

305/2839 = 0.107

Define one "map unit" (mu) as 1% recombination. Also known as one "centimorgan" (cM)

Questions:

Will any cross work?

How about

PPVV x ppvv?

PpVv x PpVv?

Unlinked genes can be on the same chromosome

The maximum recombination fraction is 50%, no matter how far apart they are.

Recombination frequency will always underestimate the actual map distance

Genetic Maps

1911 Alfred Sturtevant produced the first genetic map, of X chromosome genes in Drosophila

y w v r m

0 1.0 30.7 33.7 57.6

Compare his map with his data

y and w: 1%

y and v: 32%

y and m: 37.5 -- what went wrong here? Why is the recombination distance between y and m much less than the map distance?

Three-point crosses

Cross Gray body,Red-eye,normal wing x yellow body, white eye, miniature wing (+++ x ywm).

F1 is completely heterozygous, then backcross to the completely recessvie parent (yellow, white, miniature) to make an F2 testcross:

F2:

• +++ 758
• ++m 401
• +w+ 1
• +wm 16
• y++ 12
• y+m 0
• yw+ 317
• ywm 700

Use double recombinants to find gene order

Which are the double recombinants?

If crossovers are rare, then two crossovers are very rare. The double recombinant class will have the lowest frequency. (+w+ and y+m)

Only the middle gene is exchanged in a double crossover, so compare the double recombinant types to the parentals to see which gene is in the middle.

Draw this out if you are not convinced! It is important!

Then estimate recombination between the two pairs of loci to get map distances

Don't forget to add in the double crossovers!

To map calculate the distance between w and m, sum the recombinants (single and double) = 401+317 + 1+0 = 719/2205 = 0.326

Therefore the distance between w and m is 32.6 cM

Now do the same for the distance between y and w.