1. Chromosomes

2. Learning Objectives By the end of this class you should understand: The purpose of a karyotype The reason mitosis must be stimulated during a karyotype The notation used to describe chromosomal abnormalities The purpose of banding a chromosome The two ways to karyotype a fetus The names and types of chromosomal abnormalities The major risk factors in chromosomal abnormalities Why many developmental disorders occur as a result of chromosomal abnormality

3. Chromosomes Remember that chromosomes are the packages that our DNA is organized into Normally spread out  Only condensed during mitosis & meiosis

4. Chromatin & Centromere Chromosomes are made of a material called chromatin  A mixture of DNA and protective protein The core in the center is referred to as the centromere  Not always in the center! Sometimes off to one side  Divides the chromosome into two arms which may be uneven (long arm and short arm)

5. Why the X? Remember chromosomes are only compacted during mitosis  Mitosis doubles the chromosome from a I to an X  A visual image of the chromosome is only possible at this stage  This visual stain is called a karyotype

6. Blood Karyotype

7. Actual Karyotype Result

8. Different Banding Stains

9. Karyotyping Tissue Why karyotype at all? What tissues can be karyotyped? What is an important application of karyotyping?

10. Fetal Karyotyping!

11. Another Procedure

12. Man I thought the needle was bad! The needle method of extracting amniotic fluid to test the fetus's DNA is called amniocentesis The catheterization method is called chorionic villus sampling or CVS  Currently amniocentesis is more common and considered safer

13. What To Look For Chromosomal abnormalities come in two varieties:  The wrong number of complete sets of chromosomes (polyploidy) Haploid, diploid, triploid, tetraploid....  Missing or extra chromosomes (aneuploidy) Extra X, missing X, etc....

14. Triploidy

15. Polyploidy Often caused by completely simultaneous fertilization of egg by two sperm Invariably fatal though baby may be born disfigured but will die soon

16. Aneuploidy Many varieties of aneuploidy Typically caused by a nondisjunction in meiosis of one gamete  Extra chromosome in one sperm, missing in other

17. Chromosomal notation (Number of chromosomes)(Which chromosomes are missing or extra)(any deletions or translocations)  Often includes sex chromosomes listed Triploidy: 69,XXY Down Syndrome: 47,+21 for an extra #21 46,del(5p): deletion on the 5 th chromosome on the short arm (p)

18. Aneuploidy Varieties Monosomy  Only one of a particular chromosome  Turner Syndrome (one X) Trisomy  Three of a particular chromosomes  Down Syndrome (three #21)

19. Autosomal Trisomies Patau Syndrome  47,+13  Fatal within 1 month Edwards Syndrome  47,+18  Fatal within 2-4 months Down Syndrome  47,+21  Reduced life expectancy but not fatal

20. Sex-linked Aneuploidy Turner Syndrome  Monosomy: 45,X  Viable female, but short and sterile Klinefelter Syndrome  Trisomy: 47,XXY  Viable male, but feminine and sterile XXY Syndrome  Trisomy: 47,XYY  Few or no phenotypic variations

21. What about the others? Other chromosomal defects end in miscarriage Imagine reading a choose your own adventure book with a page missing Imagine reading a choose your own adventure book with duplicated pages! Chromosomal information is more than raw blueprints, during fetal development there is a strict order to when genes activate, and an extra chromosome screws it up

22. Maternal Age Maternal age is the largest risk factor in chromosomal abnormalities  Over 1% of births to women over 40 have chromosomal abnormalities Reason(s) still not fully understood

23. Translocation Chromosomes sometimes have an incorrect crossing over process that changes how they are attached  This is termed translocation Often but not always fatal

24. Deletion Chunks of chromosomes may fail to be copied Resulting syndromes have deletion patterns and often result in developmental issues

25. Copy Number Variants Many portions of our genome are not directly coding for protein but instead consist of long strings of repeated letters These repeated patterns may be erroneously shortened or lengthened  This is a copy number variant Increases risk for many diseases

26. Copy Number Variants

27. Have a good weekend!