1. MATTERS OF SEX Anueploidy Monosomy
having too many or too few chromosomes compared to a normal genotype
Monosomy
Possessing only 1 copy of any particular chromosomes
Monosomy, with the exception of the X chromosome is incompatable with life

2. X chromosome dosage decrease X gene products by half in females
Sex Chromosomes: females XX, males XY
Genes on X: females 2 , males 1copy
How to create equal amount of X chromosome gene products in males and females?
decrease X gene products by half in females
(e.g. humans called X-inactivation)

3. X CHROMOSOMES
This was shown by culturing cells with different karyotypes
XY XO both with 1 X chromosome
XX XXY both with 2 X chromosomes
XXX XXXX both with 3 or more X chromosomes
Looked at levels of enzymes encoded by the X chromosome

4. X LINKED GENE
G6PD, glucose 6 phosphate dehydrogenase, gene is carried on the X chromosome
This gene codes for an enzyme that breaks down sugar
Females produce the same amount of G6PD enzyme as males
XXY and XXX individuals produce the same about of G6PD as anyone else

5. G6PD GENE There are variant alleles of the G6PD gene
G6PD A G6PD B
Produce different variants of the enzyme, but both break down sugar
Female could be heterozygous for G6PD A and G6PD B
Each cell only produces 1 of the 2 forms of the enzyme

6. X CHROMOSOME
Only 1 X chromosome is active in any given cell. The other is inactive
In some cells the paternal allele is expressed
In other cells the maternal allele is expressed
In XXX and XXXX females and XXY males only 1 X is activated in any given cell the rest are inactivated

7. X CHROMOSOME
XXX embryo survives because it inactivates 2 X chromosomes and has only 1 functioning X chromosome in any given cell
Trisomy 21 can not inactivate the extra copy of chromosome 21. So you have Down syndrome
The only chromosome we can inactivate is the X chromosome

8. Table 12.3

9. 3 TYPES OF CHROMATIN Euchromatin true chromatin Heterochromatin
Chromosomal regions that possess active genes
Heterochromatin
These regions stain darker than euchromatin
Highly repetitive DNA with very few active genes
Usually found around the centromere and near the tips of chromosomes (telomeres)
Facultative Heterochromatin
Active like euchromatin in some cells and inactive like heterochromatin in other cells

10. Facultative Heterochromatin
Serves as a mechanism for a cell to shut off a portion or an entire chromosome to prevent gene expression
X chromosome is made up of facultative heterochromatin
Active X chromosome behaves like euchromatin, with active genes that are transcribed
Inactive X chromosome behaves like heterochromatin

11. Facultative Heterochromatin
The cell inactivates one X chromosome by converting the entire chromosome to heterochromatin or inactive DNA
This inactive DNA makes up the dark staining Barr body
This process occurs in females or any individual with more than one X chromosome

12. LYON HYPOTHESIS
1961 English geneticist Mary Lyon proposed this hypothesis to describe X inactivation
Consists of 5 tenants
1. Condensed X chromosome is genetically inactive
2. X inactivation in humans occurs early in development when embryo consists of about 32 cells. 1 or 2 days following fertilization

13. 5 TENANTS OF LYON HYPOTHESIS
3. At this stage in each of the 32 cells one of the X chromosomes is randomly inactivated
4. Inactivation is mitotically stable
5. Net effect of this is to equalize phenotypes in males and females for genes that are carried on the X chromosome

14. Human Chromosomes
One X chromosome in females is inactivated early in embryonic development.

17. PAR REGION NOT INACTIVATED
RSP4 gene in this region present on both X and Y chromosomes
Encodes a protein that makes up part of the ribosome
If this gene were inactivated it would reduce by half the number of ribosomes made and reduce the protein synthesized capacity of that cell by half

18. X REACTIVATION IN FEMALES
In the female fetus future germ cells undergo Lyonization along with somatic cells at the 32 cell stage
Following differentiation of female fetus, the inactivated X chromosomes are reactivated during female gametogenesis
When germ cells develop into oocytes and enter meiosis their inactivated X chromosomes become reactivated so that every egg produced has an activated X chromosome prior to fertilization

19. X REACTIVATION IN MALES
XXY Klinefelter males also reactivate the second X chromosome during gametogenisis
The presence of an extra X chromosome during early puberty causes death of male germ cells and testicular atrophy
This leads to low levels of testosterone

20. NONDISJUNCTION OF SEX CHROMOSOMES
Extra copies of the X and Y chromosomes do not cause the severe problems that extra autosomes do
Nondisjunction in mother would produce eggs that are XX or O with no X chromosome
If XX egg fertilized with X sperm get an individual who is XXX.
Individual will be sterile and have 2 Barr bodies

21. NONDISJUNCTION OF SEX CHROMOSOMES
If XX egg fertilized with Y sperm get an individual who is XXY.
Individual will be sterile male with many female body characteristics.
Known as Klinefelter syndrome
Occurs 1/500 male births
If O egg fertilized by Y sperm the zygote is non-viable
If O egg fertilized by X sperm get and individual who is XO. Turner syndrome

22. NONDISJUNCTION OF SEX CHROMOSOMES
Turner syndrome
Occurs 1/2000 live births
Sterile
Can also have non-disjunction of the Y chromosome in males
Produce sperm with 2 Y chromosomes
Fertilize an X egg develop into XYY male
Fertile males
Occurs 1/1000 males

23. MOSAICISM
Is due to a mitotic loss of 1 X chromosome in a cell early in zygotic development
This produces a combination of both XX and XO cells
The more XO cells an individual has the more severely she will be affected
Some estimates put mosaic Turner females as high as 60% to 80%

24. Newborns may not be affected
TURNER SYNDROME
Newborns may not be affected
Lag behind classmates in sexual development
Reach puberty they fail to menstruate
Small uterus
Rudimentary ovaries
Remains a primitive streak gonad
Sterile
W/O an ovary they can not produce eggs or estrogen

25. TURNER SYNDROME
Can lead fairly normal lives if they receive hormone supplements
Hormones promote breast development and other secondary sex characteristics if administered during puberty
Growth hormone adds up to 3 inches of height. Can mean the difference between an adult height of 4’11” to 5’2”