By the early 20th century… Chromosome Theory of Inheritance Haploid gametes Mendel rediscovered Morgans fly lab

Morgan’s Flies • New generation every two weeks • Four pairs of chromosomes • Plenty of visible phenotypic variation

Experiment Wild-type red-eye female x mutant white-eye male homozygous XWXW hemizygous XwY Figure 15.3 Hypothesis: white allele is on the Y

Results XWXW XwY Homo. red x Hemi. white = 100% red Hetero x Hemi red P F1 F2 Homo. red x Hemi. white = 100% red Hetero x Hemi red = F: 100% red M: 50% white

Conclusions • The white-eye allele must be on the X aka X-linked sex-linked • First solid evidence indicating that a specific gene is associated with a specific chromosome • Applies to humans too X Y X X’ carrier X Y X X X X’ X‘Y

to have a 0.25 chance of an affected daughter Affected x Carrier Takes a heterozygous carrier mom… …and an affected dad to have a 0.25 chance of an affected daughter carrier healthy affected affected

Royal Hemophilia Queen Victoria, carrier Hemophilia is an x-linked recessive condition that results in too little blood clotting factor produced, leading to uncontrolled bleeding

Red vs Green ‘Colorblindness’ results from defects in a cluster of genes on the X chromosome. As long as one normal copy of a red-absorbing gene and one normal green-absorbing gene are present, vision is normal.

X Inactivation If males have only 1 allele of each of the X chromosome, do they produce less of the protein X-linked genes produce? Nope - one X is de-activated, at random, in cells of females The Lyon hypothesis states that in cells with multiple X chromosomes, all but one are inactivated during mammalian embryogenesis[3]. This happens early in embryonic development at random in mammals A normal human female has only one barr body per somatic cell, while a normal human male has none. In mammals, males are heterogametic (XY) and females homogametic (XX). Dosage compensation is achieved by inactivation at random of one of the two X chromosomes. The heterochromatized X chromosome appears as a darkly-staining bodies attached to the nuclear membrane. The phenomenon was first described by Dr Murray L. Barr, a Canadian cytogeneticist, and heterochromatin bodies are now called Barr Bodies. [The other dark bodies within the nucleus are nucleoli, which represent repetitive rDNA genes].     Barr body testing was introduced in the 1966 Olympic games, in an effort to detect male atheletes trying to "pass" as females, to gain a competitive advantage. Teams from eastern Europe wer particularly suspect. Such allegations had been made for many years, and a number of athletes were stripped of their medals as a result of ambiguous genital sex.  Cytological testing apparently never detected deliberate fakery. It did however detect a number of cases of testicular feminization syndrome (TFS), a genetic condition in which an XY (male) zygote develops as a phenotypically female adult, due to failure of androgen receptors. Such individuals would test positive for the presence of a Barr body. It appears that in most if not all cases, the athletes were themselves unaware of their condition. mosaicism

Observation #2 • Mendel concluded that pea traits sort independent of one another • Morgan noticed that some traits do not sort independently • He proposed these traits are linked - located on the same chromosome – and that chromosomes independently assort a B c D AB C d BUT NOT ALWAYS!

Observation #3 “Chromosome pairs are observed to twist together…conceivable they could break and trade pieces” Crossing over in M2 Recombinant offspring are those that show new combinations of the parental traits

Recombination Likelihood of recombination determined by distance frequently recombined infrequently recombined linked independent Calculate % recombination to determine distance apart 1% recomb. = 1 map unit

Recombination 1% of crossover frequency = 1 unit of distance between two genes Use to create chromosome ‘maps’ of relative locations of genes