Chromosomal Mutations

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 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

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

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

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.

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.

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.

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)

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

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.

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.

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

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

XYY

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

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.

MONOSOMY – one missing - Turner Syndrome – X

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

Inversion – Gene Sequence Reversed

Translocation – Two chromosomes join long arms or exchange parts