1. Chromosomes

2. Chromosome Tightly coiled DNA form Found during mitosis and meiosis Made mostly of DNA and proteins Centromere- point of attachment Chromatids- each arm of a chromosome in replicated form Banding ▫Heterochromatin- dark area with repetitive sequences ▫Euchromatin- lighter protein- encoding area

3. Chromosome Structure: Telomeres Chromosomal tips Human chromosomes have repeats of TTAGGG Telomeres shorten during each cell division in most cells

4. Chromosome Structure: Centromere Constricted region of chromosome Region of attachment of spindle fibers during mitosis and meiosis Contains many repeats of a 171- base sequence called the alpha satellite Centromere associated proteins ▫Some form kinetochore during mitosis and meiosis ▫Centromere protein A (CENP- A)- surround centromere; are divided and continue with each chromatid during anaphase

5. Chromosome Structure Moving away from the centromere ▫Gene-rich regions ▫Subtelomeres  Gene start to taper off  More repeats start to occur

6. Chromosome Shorthand Shorthand used to locate gene on chromosome First number is chromosome number Letter (p or q) refers to the arm Second number refers to the band on that arm ▫Number gets higher as the band is farther from the centromere

7. Chromosomal Differences Size Difference ▫Chromosomes are numbered from 1 (largest)-22 (smallest) Banding differences # of Genes ▫Some chromosome have very few genes for their size, and some have a lot of genes for their size Location of Centromere

8. Location of the Centromere Metacentric- located in the middle; divides chromosomes into two equal arms Submetacentric- located slightly off of center; divides the chromosome into a long (q) arm and a short (p) arm Acrocentric- located near one end of the chromosome; divides the chromosome into a long (q) arm and a chort (p) arm Telocentric- located at the end; humans do not have these

9. Karyotype Pictorial representation of chromosomes Autosomal chromosomes are lined up by number (from largest to smallest) Sex Chromosomes are arranged last What does it tell you? ▫Sex of individual ▫Presence of chromosomal abnormality

10. Obtaining a Sample Blood sample or cheek cell sample Embryo ▫Amniocentesis ▫Chorionic Villus Sampling ▫Fetal Cell Sorting ▫Pre-implantation Testing

11. Creating a Karyotype Cell division is stopped with colchicine Cell is ruptured Cell with the most spread out chromosomes is used Chromosomes are identified with stain or FISH ▫Staining- use chromosome specific stains ▫FISH (fluorescence in situ hybridization)- fluorescent probes are attached to chromosomes; each chromosome fluoresces a different color

12. Karyotype Analysis Shorthand 46,XX First number- number of chromosomes Sex chromosomes Extra information ▫Extra chromosomes (+#)

13. Chromosomal Abnormality: Polyploidy Extra set of chromosomes Triploid (3 sets) ▫Ovum is fertilized with two sperm ▫One gamete remains diploid after meiosis Usually spontaneous abortion

14. Chromosomal Abnormailty: Aneuploidy Have a missing or extra chromosome Most are spontaneously aborted Some types can survive until birth Monosomy- missing one chromosome ▫Only one viable is XO (Turner Syndrome) Trisomy- extra chromosome

15. Nondisjunction Most aneuploidy results from nondisjunction Chromosomes fail to separate during meiosis More commonly seen in females (especially with older maternal age) Results in some gametes missing chromosomes and some having extra

16. Mosaics Aneuploidy occurs during mitosis Individual has some cells that are normal and some that are aneuploid Severity of disorder depends on when during development that it happens

17. Common Aneuploids Autosomal ▫47, X__ +21– Down Syndrome ▫47, X__ +13- Patau Syndrome ▫47, X__ +18- Edward Syndrome Sex Chromosome ▫45, XO- Turner Syndrome ▫47, XXX- triplo-X ▫47, XXY- Klinefelter’s Syndrome ▫47,XYY- Jacobs Syndrome

18. Chromosomal Alterations Structural problems of chromosomes Include ▫Deletions ▫Duplications ▫Translocations ▫Inversions

19. Deletions Deletion of part of a chromosome The larger the deletion, the more severe the disorder Microdeletions- small deletions that can create symptoms (ex: impair fertility if on Y chromosome) Cri-du-chat- deletion of part of the short arm of chromosome 5 (5p - )

20. Duplication Chromosome with repeated sections Usually repeats have to be large to be symptomatic Fragile X syndrome- expanding triplet repeat adds extra material to X

21. Translocations Two nonhomologous chromosomes exchange or combine parts Robertsonian translocation- short arms are removed from two chromosomes; long arms stick together to form one long chromsome ▫Problems for future generations Reciprocal translocation- two different chromosomes exchange parts ▫Problem for individual if gene is broken ▫Problem for future generations Translocation carrier- asymptomatic carrier of translocation

22. Robertsonian Translocation

23. Reciprocal Translocation

24. Inversion Chromosome with some genes inverted Paracentric inversion- ▫Does not include centromere ▫Crossing over can result in  Normal chromosomes  Dicentric chromosome (two centromeres)  Acentric chromosome (no centromere) Pericentric inversion- ▫Does include centromere ▫Crossing over can result in ▫Normal chromosomes ▫Abnormal chromosomes with one centromere

25. Inversion

26. Isochromosomes and Ring Chromosomes Isochromosome ▫Chromosome splits the wrong way during meiosis ▫Chromosome end up with identical arms Ring Chromosome ▫Removal of telomeres creates sticky end ▫Sticky ends attach to each other creating a ring

27. Uniparental Disomy Individual has a chromosome set where both chromosomes come from one parent Can cause problems with recessive alleles or imprinting Occurs if ▫One parent has nondisjunction resulting in a gamete with that chromosome missing ▫One parent has nondisjunction resulting in a gamete with both homologs of that chromosome ▫These two fertilize each other