Chromosome Abnormalities

Question 1

Numerical Abnormalities

Answer 1

Missing or having extra chromosomes (wrong # chromosomes)

Question 2

Structural Abnormalities

Answer 2

Chromosome is altered by deletion, duplication, breakage (problems WITHIN a chromosome)

Question 3

Aneuploidy

Answer 3

The gain or loss of a whole chromosome

(Most common chromosome abnormality in humans)

Question 4

Aneuploidy is the leading genetic cause of…

Answer 4

spontaneous miscarriage and congenital birth defects

(also seen in most tumors)

Question 5

Most common cause of aneuploidy…

Answer 5

Nondisjunction

Question 6

Non-Disjunction

Answer 6

The failure of homologs or sister chromatids to separate during cell division

(= “not coming apart”)

Question 7

Non-Disjunction can occur at: (3)

Answer 7

Meiosis I –> Anaphase I (homologs don’t separate)

Meiosis II –> Anaphase II (sister chromatids don’t separate)

Mitosis –> Anaphase (sister chromatids don’t separate)

Question 8

Non-Disjunction in Meiosis I (results)

Answer 8

2 gametes = (n + 1) = Extra chromosome
2 gametes = (n - 1) = Lost chromosome

Question 9

Non-Disjunction in Meiosis II (results)

Answer 9

1 gamete = (n + 1) = Extra chromosome
1 gamete = (n -1) = Lost chromosome
2 gametes = (n) = Normal

Question 10

Monosomic Zygote

Answer 10

(2n-1) = Lost chromosome

Normal gamete + (n - 1) gamete

Question 11

Trisomic Zygote

Answer 11

(2n + 1) = Gained Chromosome

Normal gamete + (n + 1) gamete

Question 12

What does aneuploidy affect?

Answer 12

1) Gene dosage
2) Recessive “unmasking”
3) Sterility

Question 13

Gene Dosage

Answer 13

The # of copies of a gene that are actively being expressed

–> Proportionally reflects the RNA and protein products in a cell

Question 14

Affects of aneuploidy on gene dosage

Answer 14

A missing or extra chromosome throws off the overall gene balance in the chromosome set (dosage)

–> Can lead to more or less RNA/Protein products

Question 15

Recessive “unmasking” (due to aneuploidy)

Answer 15

A missing chromosome = 1 allele determines the phenotype for those now missing genes

–> Allows any harmful recessive alleles on the single chromosome to be phenotypically expressed (hemizygous)

Question 16

Hemizygous

Answer 16

Having only one allele of a gene

Question 17

Sterility (due to aneuploidy)

Answer 17

One extra/missing chromosome interferes with the pairing of homologs during meiosis I (odd # can’t all pair)

== Halt of the cell cycle at M checkpoint

–> Meiosis can’t be completed = no gametes = sterility

Question 18

Non-Disjunction in Mitosis

Answer 18

May have a phenotypic effect depending on WHEN non-disjunction occurs:

Early in Development = Aneuploidy will be passed on to a large # of daughter cells = major phenotypic effect

Late in Development = Aneuploidy only passed onto those daughter cells (less) = possible large effect (depends)
—> Tumor cells commonly have aneuploidy

Question 19

Cause of Non-Disjunction (5)

Answer 19

Really any defects in cell division machinery:

1) Defects in kinetochore-MT attachment to chromosome
2) Defects in kinetochore complex assembly
3) Weakened meiotic/mitotic checkpoint
4) Defects in spindle pole function and/or #
5) Completely inactive checkpoints (could cause non-disjunc. of multiple or all chromosomes)

Question 20

Aneuploidy frequency in humans is _________________ BUT it usually results in _____________________

Answer 20

1) quite high (>10% of all pregnancies)

2) embryonic death

Question 21

Only certain aneuploidies can be tolerated through to adulthood, including…

Answer 21

Chromosomes X, Y, 21

Question 22

Down Syndrome

Answer 22

AKA Trisomy 21

–> An extra chromosome 21 (3 copies instead of 2)

–> Leads to extensive neuronal, intellectual, skeletal, developmental delats

Question 23

Chromosome 21

Answer 23

Smallest human chromosome (<1.5% of DNA)

–> Probably why people with abnormality on this chromosome can survive (has less of an impact than other chromosomes)

Question 24

Down Syndrome cases strongly correlate to…

Answer 24

Mother’s Age

–> The older the mother, the more common Down Syndrome offspring become

Question 25

Down Syndrome may be linked to…

Answer 25

Age dependent abnormality in the M (spindle) checkpoint during meiosis I that is leading to non-disjunction

Question 26

Fetal Genetic Testing

Answer 26

There are screening and then diagnostic tests that can be run

Question 27

Screening Tests

Answer 27

Imaging / Blood tests (non-invasive)

Question 28

Diagnostic Tests (2)

Answer 28

1) Amniocentesis
2) Chorionic Villus Sampling (CVS)

Question 29

Amniocentesis

Answer 29

Needle inserted into uterus to get amniotic fluid sample which contains fetal cells

–> Sample is then sent to undergo biochemical testing and/or karyotyping

–> Higher risk + can be done later

Question 30

Chorionic Villus Sampling (CVS)

Answer 30

Narrow suctioned tube inserted into the cervix and through to the uterus to get a small sample of the placenta

–> cells of the chorionic villi are derived from the fetus

–> The sample can then undergo biochemical testing and/or karyotyping

–> Lower risk + can be done earlier