Chromosome+Structure+and+Analysis

=**Objectives**=


 * 1. Classify the human chromosomes.** (p.129)

Human chromosomes are classified by size and location of centromeres on chromosomes:

Group A: Chromosomes 1-3; metacentric Group B: Chromosomes 4 and 5; submetacentric Group C: Chromosomes 6-12; submetacentric Group D: Chromosomes 13-15; acrocentric with satellites Group E: Chromosomes 16-18; short metacentric or submetacentric Group F: Chromosomes 19 and 20; short metacentric Group G: Chromsomes 21 and 22; short acrocentric chromosomes, 21 is shorter than 22

X chromosomes can be placed with Group C; Y chromosomes which have no satellites can be placed with Group G.


 * 2. Review the basic concept of chromosome banding.** (p.125-126, 132)

__Preparation__ (1) Draw blood (2) Remove RBCs (which don't have any DNA); ficoll separation of lymphocytes for culture (3) Culture in phytohemagglutin for 2-3 days - phytohemagglutin is a mitogen that encourages faster cell division (4) add colchicine - inhibits microtubule formation to prevent chromosome separation (5) treat in hypotonic solution (6) drop cell suspension on slide (explodes because of hypotonic treatment) (7) air dry (8) stain using specific technique:

Q-bands: quinacrine staining - bright flourescent bands G-bands: giemsa staining after chromosome pretreatment - dark G-bands correspond with most bright Q-bands R-bands: various techniques - inverse pattern compared to G and Q; useful for defining ends of chromosomes T-bands: various technuqies - highlights end of chromosomes C-bands: Protein/DNA extraction with Giemsa staining - highlight centromeric regions NOR: silver staining - stains nucleolus organizer regions (acrocenteric chromosomes in humans)


 * **Characteristic** || **R-bands** || **Q/G-bands** || **C-bands** ||
 * Location || Chromosome arms || Chromosome arms || Centromeres, distal Y ||
 * Base composition of DNA || GC-rich || AT-rich || AT-rich and some GC-rich ||
 * Type of chromatin || Euchromatin || Heterochromatin || Heterochromatin ||
 * Time of DNA replication || Early S || Mid to late S || Late S ||
 * Transcriptional activity || High; housekeeping || Low; tissue-specific || Absent ||


 * 3. Interpret in a diagram of a chromosome: arm region, band, and centromere.** (p.123)



(1) chromatid (2) centromere (3) p arm (p for petite) (4) q arm


 * 4. Explain the correct karyotype reporting procedure.** (p.127)

To report a given karyotype, record the total chromosome number, sex chromosomes. If there is an extra chromosome, record the total chromosome number, sex chromosomes, +extra chromosome

__Examples__ Normal: 46, XY Trisomy 21: 47, XY, +21

For chromosome banding notation, record (1) chromosome number (2) arm (3) region number (4) band number (5) sub-band number as a decimal

__Example__ 1Q25.1: chromosome 1, Q arm, region 2, band 5, sub-band 1


 * 5. Illustrate the numerical chromosome abnormalities: give one example.** (p.139)

Numerical chromosome abnomalities are abnormalities involving an incorrect number of chromosomes. Ploidy can result from failure of the egg to expel its second polar body upon completion of the second meiotic division at fertilization or polyspermy when two sperm penetrate the egg when the cortical granule reaction fails to respond in time. Trisomy can result from non-disjunction of chromosomes either during meiosis I or meiosis II.


 * Karyotype||Comment||
 * 92, XXYY||Tetraploidy||
 * 69, XXY||Triploidy||
 * 47, XX, +21||Trisomy 21||
 * 47, XX, +18||Trisomy 18||
 * 47, XX, +13||Trisomy 13||
 * 47, XX, +16||Trisomy 16||
 * 47, XXY||Klinefelters syndrome||
 * 47, XXX||Trisomy X||
 * 45, X||Turner syndrome||
 * 49, XXXXY||Variant of Klienfelters syndrome||


 * 6. Explain major chromosome aneuploidy syndromes compatible with live birth.** (p.147)

Trisomy 21 is a major chromosome aneuploidy syndrome can be compatible with live birth. Trisomy can result from non-disjunction of chromosomes either during meiosis I or meiosis II.

Characteristics: mental retardsation, flat nose, close-set eyes, slanding eyelids, protruding tongue, 1 in 800-1000 births, due to maternal age with 85% maternally derived abberration likelihood.


 * 7. Explain structural chromosome abnormalities and how those happen.** (p.147-148)

Chromosome structural abnormalities are errors within a chromosome that can result from chromosomal breakage. Breakage of chromosomes creates two unstable, sticky ends that can be incorrectly rejoined by repair mechanisms. Breakages can be caused by exposure to ionizing radiation, rare inherited conditions, x-rays, and chemical mutagens.

Structural aberrations that can occur include:
 * 1) Deletion
 * 2) Ring chromosomes
 * 3) Duplications
 * 4) Inversions
 * 5) Centric fragments
 * Acentric fragments lack a centromere and are lost because they cannot bind the the spindle apparatus during mitosis
 * 1) Translocation