MATTERS OF SEX

1. MATTERS OF SEX • Anueploidy • 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 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 • 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. 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”