Extending Mendel: X-linked genes

Morgan and the fruit fly

• Reciprocal crosses between white and red eyed flies produced different results depending on whether the white eye color was in the female or the male parent.

Sex determination in Drosophila

• XX/XY. •  It is the balance between X

chromosomes and autosomes that determines sex: females with 2 X chromosomes; males with one.

• What sex would a fly with XYY be? XXY?

• How about X–?

SO what if 2 genes are on the same chromosome: will they

assort independently?

Morgan’s experiment–linked genes should be inherited together

wy+/wy+ w+y/w+y

wy+ w+y

Results

wy+/Y : 4292

w+y/Y : 4605

wy/Y : 86

w+y+/Y : 44

How did we get recombinants among progeny?

But why so few recombinants?

Genetic mapping

• Morgan reasoned that if the distance between 2 genes determined the frequency of crossing over and therefore of recombinants showing up, then crosses involving genes on the same chromosome could be used to map relative position.

• A heterozygous, but phenotypically wild-type fruit fly (gray body color and normal wings) was mated to a black fly with vestigial wings. The offspring had the following phenotypic distribution: wild type, 720; black-vestigial, 780; black-normal, 280; gray-vestigial, 220. What conclusion(s) is (are) likely from these results?

Can linked genes assort independently?

Incomplete dominance

Another example of incomplete dominance

Codominance Glycophorin A gene in humans spans the plasma membrane of the red blood cells. There are 2 alleles, M and N based on 2 aa differences. But both appear on the cell surface in heterozygotes

So why the variety of dominance relationships?

• Completely recessive alleles are usually non functional.

• Complete dominance occurs when one allele is enough.

• Incomplete dominance occurs when one allele does not suffice.

• Codominance occurs when both alleles combine to create the phenotype.

Are there always 2 alleles per gene?

Human Leucocyte Antigen–HLA • Code for the MHC proteins that

occur on the cell surface. •  Several loci exist each with many

codominant alleles. • Variation occurs particularly

commonly at the site where the molecule binds to antigens. MHC class I

Major Antigens HLA A 580 HLA B 921 HLA C 312 Minor Antigens HLA E 9 HLA F 21 HLA G 28

MHC function

• Non self recognition • Antigen presentation

Gene Interactions

• When a product from a gene interacts with products form other genes, particular combinations of alleles of the two genes can produce distinct effects. I.e., the phenotype of one gene depends on the phenotype of the other.

cat coat color

• A coat color gene B codes for black pigment while another allele b codes for brown. But the gene C (full color gene) determines whether pigment can be produced independent of color. So a cat that is BBcc will be white even though it has a gene to make pigment. Similarly bbcc and Bbcc are white. The B gene is hypostatic to the C gene; the c gene is epistatic to the b gene.

Pleiotropy

• When a gene has more than one phenotypic effect. • E.g. Marfan syndrome (see text). • Full color gene (tyrosinase) in cats and other

mammals

• Because many gene products may interact differently and play slightly different roles depending on the cell they are in, pleiotropy may be more the rule than the exception.

Nature versus Nurture

• Genes are not the sole determinants of phenotype; depending on the environment a gene may have very different implications.

• E.g., PKU, diabetes. Both are heritable through a single gene but the phenotype differs depending on environment (diet, insulin injection)

Quantitative Traits

• Mendel studied genes that cause qualitative difference (yellow vs green seeds). Many traits are quantitative such that individuals differ by degree, not by kind.

• E.g. height, skin color, etc

Pedigree analysis