Chromosome Abnormalities Flashcards
(30 cards)
Numerical Abnormalities
Missing or having extra chromosomes (wrong # chromosomes)
Structural Abnormalities
Chromosome is altered by deletion, duplication, breakage (problems WITHIN a chromosome)
Aneuploidy
The gain or loss of a whole chromosome
(Most common chromosome abnormality in humans)
Aneuploidy is the leading genetic cause of…
spontaneous miscarriage and congenital birth defects
(also seen in most tumors)
Most common cause of aneuploidy…
Nondisjunction
Non-Disjunction
The failure of homologs or sister chromatids to separate during cell division
(= “not coming apart”)
Non-Disjunction can occur at: (3)
Meiosis I –> Anaphase I (homologs don’t separate)
Meiosis II –> Anaphase II (sister chromatids don’t separate)
Mitosis –> Anaphase (sister chromatids don’t separate)
Non-Disjunction in Meiosis I (results)
2 gametes = (n + 1) = Extra chromosome
2 gametes = (n - 1) = Lost chromosome
Non-Disjunction in Meiosis II (results)
1 gamete = (n + 1) = Extra chromosome
1 gamete = (n -1) = Lost chromosome
2 gametes = (n) = Normal
Monosomic Zygote
(2n-1) = Lost chromosome
Normal gamete + (n - 1) gamete
Trisomic Zygote
(2n + 1) = Gained Chromosome
Normal gamete + (n + 1) gamete
What does aneuploidy affect?
1) Gene dosage
2) Recessive “unmasking”
3) Sterility
Gene Dosage
The # of copies of a gene that are actively being expressed
–> Proportionally reflects the RNA and protein products in a cell
Affects of aneuploidy on gene dosage
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
Recessive “unmasking” (due to aneuploidy)
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)
Hemizygous
Having only one allele of a gene
Sterility (due to aneuploidy)
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
Non-Disjunction in Mitosis
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
Cause of Non-Disjunction (5)
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)
Aneuploidy frequency in humans is _________________ BUT it usually results in _____________________
1) quite high (>10% of all pregnancies)
2) embryonic death
Only certain aneuploidies can be tolerated through to adulthood, including…
Chromosomes X, Y, 21
Down Syndrome
AKA Trisomy 21
–> An extra chromosome 21 (3 copies instead of 2)
–> Leads to extensive neuronal, intellectual, skeletal, developmental delats
Chromosome 21
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)
Down Syndrome cases strongly correlate to…
Mother’s Age
–> The older the mother, the more common Down Syndrome offspring become
