Numerical Chromo Abnormalities

Question 1

Meiosis vs. mitosis

Answer 1

1. ) In meiosis paternal and maternal derived homologous chromos pair in prophase I, whereas they segregate independently in mitosis
2. ) Reciprocal recombination b/w maternal and paternal sister chromatids generate chiasmata (physical links) between homologs. But in mitosis, recombo is rare between homologues. (in meiosis its required for success)

Question 2

Chromatid

Answer 2

One copy of a duplicated chromosome, bound to other copy by centromere

Question 3

Recombination

Answer 3

Maternal and paternal homologs are paired and form “bivalents”… requires synaptonemal complex formation that promote inter-homolog interactions.
Recombo at this stage generates physical links (chiasmata), usually get 2-3 recombo events on each chromosome.

Question 4

Synaptonemal complex

Answer 4

Assembled in prophase I, disassembles at end so bivalents only held together by chiasmata.
Important for recombo.

Question 5

Which is most error prone step?

Answer 5

Meiosis I. When homologs segregated to opposite poles of the cell.
Chromosome nondisjunction occurs often.

Question 6

Meiosis I and II

Answer 6

Meiosis I: homologous chromos condense and cross-over, and then are separated (randomly! so many diff combos).
Meiosis II: sister chromatids separate

Question 7

Metacentric, submetacentric, acrocentric

Answer 7

Metacentric: centromere near middle
Submetacentric: centromere slightly removed from center
Acrocentric: centromere is near the end of the chromo

Question 8

Aneuploidy

Answer 8

Cells have abnormal chromosome number.

Frequently from non-disjunction.

Question 9

Monosomy and trisomy

Answer 9

Lack or have extra copy of a chromosome.

Monosomies: lethal (except 45X turner)
Trisomies, fetus develops but often aborts (except 13, 18, 21). Risk factor is increasing maternal age.

Question 10

Most common cause of trisomy 21?

Answer 10

Maternal nondisjunction in meiosis I

Question 11

How does nondisjunction happen?

Answer 11

1. ) NEED recombo to tether homologous chromos in meiosis I. So issues in this associated with segregation problems.
   - They are related to chiasmata position (cross-over too near or far from centromere is bad. Too far= spindle issues. Too close/too many = entanglement and what looks like issues in MII).
   - Frequency of cross over events. Reduction or absence of them increases likelihood.

Question 12

Maternal age effect

Answer 12

2 hit hypothesis: 1st is diminished recombo (lack of chiasma or their mislocalization), 2nd egg being unable to successfully segregate chromos in presence of unfavorable segregation. It increases MI non-disjunction.

Terminalization: as you age cohesion b/w replicated sister chromatids could degrade (remember women sit in meiosis I until fertilization), allows chiasmata to terminalize, compromises adhesion b/w sister chromatids.. get premature separation and aneuploidy.

Question 13

Premature separation of homologs/sister chromatids?

Answer 13

Aneuploidy!

Question 14

Function of cohesin complex

Answer 14

In meiosis (issue with maternal age) it ensures cohesion b/w sister chromatids and maintenance of inter-homolog associations distal to cross-over sites.

Question 15

Edwards Syndrome

Answer 15

Hand positioning, diaphragmatic hernias, intrauterine growth retardation.
Trisomy 18.

Question 16

Pata Syndrome

Answer 16

characteristic facies, congenital malformations (clefts, polydactyly)
Trisomy 13

Question 17

Klinefelter Syndrome

Answer 17

Trisomy X. 47, XXY.

Tall stature, hypogonadism, sterility.

Question 18

Turner Syndrome

Answer 18

Short stature, webbed neck, edema of hands and feet.

Question 19

Mosaicism

Answer 19

2 genetically diff cells in a tissue derived from one zygote. Results from mutations arising in single cells (in prenatal or postnatal life).
Mutations that occur in mitosis are passed on to daughter cells.

Question 20

Causes of mosaicism

Answer 20

Somatic chromosomal errors during development (47 XX + 21/46, XX… mosaic down syndrome); 46, XX/46XY (true hermaphroditism)
Somatic chromosomal mutation is common way cells start to overexpress oncogenes or lose tumor suppressor genes.

Question 21

Germ line mosaicism

Answer 21

occurs when somatic mutation early in development generates a mutant sub-population of germ cells.

Female/male germ line cells undergo many mitotic divisons before differentiating into stem germ cells that enter meiosis. So you can have offspring with “de novo” mutations.