1. The genetics of sex

2. Mitosis
Meiosis I
Meiosis II
Ploidy at start
Preceded immediately by DNA synthesis
Chromosomes condense
Homologous chromosomes synapsis
Genetic material is exchanged
Homologous chromosomes separate
Sister chromatids separate
Daughters have novel genetic composition
Ploidy at end

3. When does meiosis occur in humans?
What happens when there are errors in meiosis?
What determines sex in humans?
How do males and females balance their gene products?

4. Meiosis in mammalian males doesn’t begin until puberty
Germ cells
Male germ cells continue to proliferate throughout adult life
Four similar spermatozoa are produced from each germ cell

5. Meiosis in mammalian males begins after puberty
Germ cells line the perimeter of the tubule
Somatic (non-germ) cells nurture the developing sperm
As sperm mature, they move toward the central lumen
Process takes ~3 weeks to a month

6. Females are born with ~1 million oocytes
More than half die before puberty
A cohort of follicles begins to grow in response to hormones each month (takes ~1 year) – most will die
Dominant oocytes resume meiosis and arrest in metaphase II when they are ovulated
Prophase I arrest
Meiotic divisions are asymmetric, producing a single large gamete, the oocyte

7. Oocytes are surrounded by many supporting cells within a follicle
Ovarian follicles at various stages of differentiation can be seen in a cross-section of an ovary.
Period of growth from a primary follicle (2) to ovlulation (4) takes about a year

8. In mammals, there are important distinction between meioses in males and females. Which of the following is NOT true?
In females, oocytes are arrested in meiosis for most of the lifespan.
Meiosis occurs throughout the lifespan of human males.
Male meiosis produces four spermatozoa, each with a unique genetic composition
Female meiosis produces one functional oocyte and three small, haploid polar bodies
Meiosis begins earlier in females than in males

9. When does meiosis occur in humans?
What happens when there are errors in meiosis?
What determines sex in humans?
How do males and females balance their gene products?

10. Aneuploidies arise from errors in either meiosis I or meiosis II
Segregation errors cause cells to have too many or two few chromosomes

11. Error in meiosis I
Homologs don’t separate or don’t attach to spindle
Trisomies (too many chromosomes)
Monosomies (too few chromosomes)
Error in meiosis II
Centromeres don’t separate or don’t attach to the spindle

12. Human genome encodes ~21,000 proteins Chromosome Protein coding genes
Few human trisomies are tolerated – may relate to the number of genes that encode proteins
Human genome encodes ~21,000 proteins
Chromosome
Protein coding genes
Incidence at birth
% survival after 1 year 1
2102
13 (Pateau)
318
~1/15,000
<5%
18 (Edward)
268
~1/8000
21 (Down)
225
~1/800
85% 22
431
very rare X
815
1/1000 females
very good
Y (XYY – Jacob’s) 45
1/1000 males
Sex chromosomes aneuploidies are tolerated

13. Individuals with Klinefelter Syndrome (47, XXY) are males, but sexual development is impaired
Some male and female development, but no sperm
2 in 1000 male births

14. Individuals with Turner Syndrome (45, X) are females
only viable human monosomy
Female development, but no eggs.
1 in 3000 female births
Symptoms may relate to haploinsufficiency for multiple gene products

15. When does meiosis occur in humans?
What happens when there are errors in meiosis?
What determines sex in humans?
How do males and females balance their gene products?

16. Y chromosome genes determine male-specific traits
The presence of the Y chromosome normally determines whether a human is male or female
Y chromosome genes determine male-specific traits
Analysis of chromosomes in intersex individuals was critical to understanding sex determinants

17. The X and Y chromosomes pair up during male meiosis
Tips of the Y chromosome (pseudoautosomal region) exchange with the X chromosome during meiosis
Much of the Y does not recombine with the X – this region hosts genes important for male fertility
Autosome: non-sex chromosome
Humans have 22 pairs of autosomes

18. Y chromosome is gene-poor, but retains important genes
Other genes remain similar to those on the X - mostly housekeeping genes
Y chromosome is a degenerate X chromosome - many inversions and deletions have occurred over evolutionary time
Y chromosome has key genes important for male development and fertility

19. Functions and evolution of the Y chromosome
HHMI Holiday lecture on sex determination (17 min.) Lecture 4, Parts 7-15

20. When does meiosis occur in humans?
What happens when there are errors in meiosis?
What determines sex in humans?
How do males and females balance their gene products?

21. Mammals use X-inactivation to ensure male and females have similar amounts of proteins produced from X chromosome genes
The Barr body: the inactive X is highly condensed and can be visualized with the light microscope
Female
Male
Canadian scientists Murray Barr and Ewart Bertram noted that male and female neurons could be distinguished by the absence (male) or presence (female) of a heterochromatic structure
Barr and Bertram (1949) Nature :

22. How many Barr bodies would you expect in an XXY male with Kleinfelter’s syndrome?
None
One
Two
Three

23. How many Barr bodies would you expect in an individual with Trisomy X?
None
One
Two
Three

24. X-inactivation is an example of epigenetics
Calico cats provide a familiar example of X inactivation
Calico cats are always females
Alleles for orange and black coat color are on the X
Cats are mosaics - one X chromosome is inactivated in each cell in a random pattern established in early development
(White spotting pattern determined by another gene)
X-inactivation is an example of epigenetics

25. X-inactivation and calico cats

26. A female calico cats mates with a black male cat and has a litter of 10 kittens. The female kittens are:
All black
All calico
Half black and half orange
Half black and half calico
Half orange and half calico

27. A female calico cats mates with a black male cat and has a litter of 10 kittens. The male kittens are:
All black
All calico
Half black and half orange
Half black and half calico
Half orange and half calico

28. Discuss: Why do individuals with Turner’s syndrome have reduced fertility and other symptoms?