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.

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

Made up of: DNA, replication enzymes, histone proteins, transcription factors, and RNA.

Organized according to size and centromere location.

Centromere = point of attachment for spindle fibers during mitosis and meiosis. Repetitive sequence that may help orient chromosomes during division.

Metacentric = equal armsSubmetacentric = one long arm and one short arm

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.

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.

Portrait of a Chromosome

Figure 13.1

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.

GET CELLS: Any cell other than red blood cells (no nucleus).

White blood cells (easy)

Red blood cell (left) and white blood cell (right)

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)

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.

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

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.

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.

TRISOMY – an extra chromosomeDown syndrome – Trisomy 21Klinefelter syndrome – XXY, XXXY, XXXXY or XXX, XXXX, etc.

XYY Syndrome Trisomy 13 & 18

MONOSOMY – one missing - Turner Syndrome – X

Deletion – Part of chromosome missing

Duplication – Part of chromosome present twice

Inversion – Gene Sequence Reversed