1. Chromosomal Mutations

2. Chromosomal Mutations
A mutation is considered chromosomal if it is large enough to be seen with a light microscope using stains and/or fluorescent tags to highlight missing, extra, or moved material.
Too much or too little genetic material, particularly on the autosomes, can cause syndromes.

3. Cytogenetics Cytogenetics is a subdiscipline within genetics
Deals with chromosome variations
In general, excess genetic material has milder effects on health than a deficit
(Trisomies are not as bad to have as a monosomy)
Still, most large-scale chromosomal abnormalities present in all cells disrupt or halt prenatal development

4. 13.1 – Chromosomes
Made up of: DNA, replication enzymes, histone proteins, transcription factors, and RNA.
Organized according to size and centromere location.

5. Metacentric = equal arms
Centromere = point of attachment for spindle fibers during mitosis and meiosis. Repetitive sequence that may help orient chromosomes during division.
Metacentric = equal arms
Submetacentric = one long arm and one short arm

6. Telomere = A chromosome tip
Acrocentric = pinches off only a small amount toward one end
Telocentric = centromere at one end
Telomere = A chromosome tip
Position of the centromere in (A) metacentric; (B) submetacentric; (C) acrocentric; and (D) telocentric chromosomes.

7. Euchromatin – lighter-staining. Protein encoding genes.
Stains are used to distinguish chromosomes.
Heterochromatin – darker- staining region. More highly coiled & more repetitive. May play a role in maintaining structure. (near centromere and telomeres)
Euchromatin – lighter-staining. Protein encoding genes.

8. Portrait of a Chromosome
Figure 13.1

9. Karyotype – size-order chart of chromosomes. They can:
confirm diagnosis.
I.D. relatives with specific chromosomal abnormalities.
sometimes reveal the effects of environmental toxins.
clarify evolutionary relationships. Banding patterns are more similar in species that are more closely related.

11. 13.2 - HOW DO WE LOOK AT CHROMOSOMES?
GET CELLS: Any cell other than red blood cells (no nucleus).
White blood cells (easy)
Red blood cell (left) and white blood cell (right)

12. FETAL CELLS commonly tested
AMNIOCENTESIS (1966) needle passes through abdomen and fetal cells are obtained from the amniotic fluid.
Chorionic Villus Sampling
Fetal Cell Sorting (from mom’s blood)

13. Put cells in a hypotonic solution so they fill with water.
Drop the cells onto a slide and add a glass coverslip.
Photograph cells and make a print.
Cut out chromosomes and arrange by size. Now use software.

14. Count the number. (46 in humans)
Use a combination of stains and DNA probes (labeled piece of DNA that binds to its complementary sequence)
Shorthand - # of chrom, Sex chrom, type of error

15. CHROMOSOMAL SYNDROMES
Most frequent cause of spontaneous abortion.
POLYPLOIDY – Extra chromosome sets
2/3 from egg fertilized by two sperm.
Also from formation of a diploid gamete.
Some infants survive for a few days, but most are never born.

16. Most result in spont. Abortion.
ANEUPLOIDY – An extra or missing chromosome
“not good set” (Euploid – “good set”)
Result from NONDISJUNCTION (chrom. not separated properly during meiosis)
Most result in spont. Abortion.
Most survivors have mental retardation.
Sex chromosome aneuploidy is less severe.

18. TRISOMY – an extra chromosome
Down syndrome – Trisomy 21
Klinefelter syndrome – XXY, XXXY, XXXXY or XXX, XXXX, etc.
XYY Syndrome
Trisomy 13 & 18

19. XXY – Klinefelter’s Syndrome
1:500 to 1:1000 live male births
Often infertile, more feminine features, less testosterone

20. XYY

22. Trisomy 13 “Patau syndrome”
Survival beyond the first year is uncommon.
Cleft lip, extra toes, extra tissue near the eye

24. Trisomy 18 – “Edward’s Syndrome”
* Characteristic = small face and small chest, overlapping fingers with clenched fists, and a left-sided clubfoot.
* It is uncommon for fetuses with this condition to survive, so the incidence is only 1 in 8000 live births. It is rare for babies to survive for very long if liveborn because of the multitude of anomalies that are usually present.

25. MONOSOMY – one missing - Turner Syndrome – X

26. Duplication – Part of chromosome present twice
Deletion – Part of chromosome missing
Duplication – Part of chromosome present twice

27. Inversion – Gene Sequence Reversed

28. Translocation – Two chromosomes join long arms or exchange parts