Chromosome “Wrap-up”

1. Chromosome “Wrap-up”

2. How does so much DNA fit in Nucleus? • Even the shortest human chromosome contains more DNA than would fit into the nucleus (46 b. base pairs) • If it weren’t condensed, it would take up 1.5 cm of length • Chromosomes must condense to fit in nuclei

3. “Packing” a punch! • The smallest chromosome DOESN’T take up 1.5 cm, it only takes up 2 micrometers during its condensed state of mitosis/meiosis • How? • DNA is organized into a hierarchy of “packing”

4. Levels of DNA Packing in Chromosomes • Level 1 • 4 nm DNA is wound around a protein core to look like a bead called a “nucleosome” 10 nm thick

5. Levels of DNA Packing in Chromosomes • Level 2 • Further coiling results in 30 nm nucleoprotein fibers • Looped addtionally to form metaphase chromosomes 700nm

6. DNA coiling

7. The Coils of Chromosomes

8. Basic chromosome structure Q arm of chromosome P arm kinetochore chiasmata nucleosome Telomere Nucleoprotein fiber Recombinant DNA

9. Chromosomes Carry Genes CHROMOSOMES • Human chromosomes are • stored in the nucleus • Chromosomes have DNA wrapped around special histone proteins. • “Beads on string”: nucleosomes organize DNA in human genome DNA Base-Pairs: A-T G-C DNA Helix

10. How Many Chromosomes Are There? • Bacteria usually have one circular • chromosome and no nucleus • Organisms with nuclei have variable numbers of chromosomes • depending on the species: • Mosquito 6 • Chimpanzees 48 • Goldfish 94 http://gnn.tigr.org/whats_a_genome/Chp1_3_1.shtml

11. You Inherited Two Copies of Each Chromosome, One from Mom and One from Dad One copy of chromosome #3 from Mom One copy of chromosome #3 from Dad • You inherited two copies of each gene, one from Mom and one copy from Dad. All 46 Human chromosomes together is called a human karyotype. The X and Y chromosomes are the sex chromosomes. The 22 chromosomes (not the sex chromosomes) are called autosomes.

12. Human Cells Have 22 Sets of Paired Chromosomes 22 SETS OF PAIRED AUTOSOMES EACH 2 sex chromosomes 2 sex chromosomes Almost every cell in your body (except RBC, eggs, sperm) has two sets of genes carried on 22 sets of paired chromosomes, plus 2 sex chromosomes.

13. ? What is the Relationship Between DNA and Chromosomes?

14. DNA CELL CHROMOSOMES DNA G E N E A DNA Helix NUCLEUS DNA Each Chromosome Contains Hundreds of Genes! GENE 1 GENE 2 GENE 3 GENE 6... GENE 5 GENE 4

15. DNA is Packaged Into Chromosomes DNA double helix GENE (blue) Several GENES along a length of DNA DNA is coiled around proteins (more on this later) Small region of “unwrapped” chromosome Loosely wrapped DNA in chromosome Tightly wrapped chromosome Adapted from Alberts et al. Molecular Cell Biology

16. Chromosomes are Dynamic Structures Fruit Fly Human Chromosomes Metaphase Chromosome CONDENSED EXTENDED

17. One Human Chromosome Contains One ds DNA Helix ONE double-stranded (ds) DNA molecule extends from one end of the chromosome to the other end of the chromosome. Short arm (‘p’) Centromere Long arm (‘q’) The chromosome on the left has duplicated (replicated). How many ds DNA helices does it contain?

18. Human Chromosomes Have Two Ends and a Middle! Centromeres are Stained The ends of a linear chromosome are called telomeres. Telomeres play a special role when the chromosome DNA duplicates during cell division. Telomere Centromere Telomeres are Stained Centromeres are usually in the middle of the chromosome, but can be near one end. What essential role do centromeres play in cell division? Telomere

19. Human Chromosome Karyotypes 1 2 3 4 6 7 8 9 10 11 Which gender results from inheriting these chromosomes? Banding patterns on chromosomes represents different staining of A-T and G-C rich regions in the DNA

20. What Happens to Chromosomes and Genes When Cells Divide? CENTROMERE ONE DOUBLE-STRANDED DNA HELIX DNA Replication (Duplication) DNA Replication (Duplication) TWO DOUBLE- STRANDED DNA HELICES Telomeres are needed to duplicate the very ends of the chromosomes CENTROMERE

21. Before A Cell Can Divide To Make Two Cells, It Must Duplicate It’s Genes, Chromosomes and DNA Chromosomes duplicate and line-up on metaphase plate [46 x 2 = 92] 46 chr Chromosomes move to opposite poles Start here chromosomes attach to spindle fibers 46 chromosomes In each daughter cell

22. Centromeres are Critical for Chromosome (Gene) Inheritance Metaphase Anaphase Spindle fibers attach to centromeres on the chromosomes. Molecular motors at centromere move the chromosome along the spindle fiber to the pole. Spindle Pole Spindle Microtubule Centromeres

23. Down Syndrome: A Consequence of Centromere Failure and Incorrect Chromosome Inheritance A special type of cell division (meiosis) generates germ cells: eggs and sperm A mistake in meiosis during egg production creates an egg with one additional chromosome (#21) Chromosome number 46 46 46 46 46 46 meiosis meiosis germ cells germ cells 23 23 24 23 23 23 24 23 fertilization fertilization fertilized zygote fertilized zygote 46 47

24. How Does Down Syndrome Affect People Who Inherit an Extra Copy of Chromosome 21? Down Syndrome identified by John Langdon Down (1866) who noticed that some people looked similar although they were not biologically related. Down Syndrome features: a broad flat face, small nose and variable levels of mental impairment. Called “Mongolism” in 1866 but now properly called Down Syndrome. Down Syndrome is caused by Trisomy 21 (3 copies of chr 21) Extra copy of chromosome 21 causes the “Down” characteristics. Most Down people have 47 chromosomes in every cell. Others have 46 chromosomes in some cells and 47 chromosomes in other cells (mosaic) and have less severe Down symptoms. http://www.genetics.com.au Genetics Fact Sheet #24A

25. Down Syndrome Risk Increases with Age of Mother Down Syndrome occurs more frequently in women over age 35 years. Age of Mother: 20-24 yrs risk is 1 in 1474 35 yrs risk is 1 in 384 40 yrs risk is 1 in 112 45 yrs risk is 1 in 28 Note: Risk of having child with a chromosome abnormality also increases with age of mother: 20-24 yrs 1 in 506 35 yrs 1 in 179 40 yrs 1 in 64 45 yrs 1 in 19 Down Syndrome can also be caused by inheriting an extra chromosome 21 from the father’s sperm. Risk does not increase with age. There is no cure for a child with Down Syndrome. There are pre-natal screening tests available for Down Syndrome. Discuss this in unit on genetic testing. Scientists are looking for the regions of chromosome 21 that are most likely to be involved in causing Down Syndrome.

26. Other Genetic Disorders Caused by Chromosome Abnormalities Klinefelter Syndrome: 46,XXY (“Normal” is 46,XY) Klinefelter affects only boys with risk of 1 in 500 to 1 in 1000 males born. (fairly common) Symptoms include sparse facial hair, inability to form sperm (infertility but sexuality is “normal”), learning difficulties Klinefelter caused by a mistake in segregation of the X chromosome at or soon after conception. When the mistake occurs after conception, Klinefelter boys can be mosaic (have some 46,XY cells and some 46,XXY cells) Klinefelter is not related to the age of the mother or father at conception. There is no cure although treatment with testosterone can reduce symptoms. There are pre-natal screening tests available. Discuss this in unit on genetic testing. Klinefelter occurs sporadically for unknown reasons. http://www.genetics.com.au Genetics Fact Sheet #24B