Numerical Chromosomal Abnormalities

Question 1

What are the events in meiosis that produce genetic variability among offspring?

Answer 1

• Crossing over
• Assortment of alleles
• Reduction in genetic material from diploid to haploid

Question 2

What are the two key differences between mitosis and meiosis?

Answer 2

1 - paternally- & maternally-derived homologous chromosomes pair at the onset of Prophase I (the two homologs segregate independently in mitosis)

Question 3

What are bivalents and why are they important?

Answer 3

Bivalents are structures in which mat & pat homologous become paired along their entire length
(brought together by the synaptonemal complex)

=> 2-3 crossovers occur on each chromosome
=> genetic reassortment b/w chromosomes

Question 4

What is the synaptonemal complex?

Answer 4

A proteinaceous structure that promotes inter-homolog interaction (necessary for bivalent structures)

It disassembles at the end of Prophase I
=> bivalents only held together by chiasmata

Question 5

What is the most frequent mutational mechanism in humans, and during which stage does it occur?

Answer 5

Chromosome Nondisjunction

during Meiosis I (most error-prone step)

Question 6

What are the three classifications for chromosomes?

Answer 6

1. Metacentric = centromere is in the middle, chromosome arms are approx same length
2. Submetacentric = centromere slightly removed from center
3. Acrocentric = centromere is near one end

Question 7

How else are chromosomes classified?

Answer 7

Cytogenetically, based on banding patterns observed microscopically

Unique banding patterns => unequivocal identification of each chromosome

Question 8

What is chromosome nondisjunction?

Answer 8

The missegregation of chromosomes at metaphase (in either mitosis or meiosis) in which daughter cells receive extra or fewer chromosomes

Question 9

What is aneuploidy?

Answer 9

A condition in which cells contain an abnormal chromosome number

(frequently the result of chromosome nondisjunction)

Question 10

What type of errors predominate almost all trisomies, and when do they occur?

Answer 10

maternal errors in the first meiotic division

Question 11

Disturbances in the recombination pathway are associated with abnormalities in chromosome segregation in the first mitotic division. How does the location of chiasmata affect nondisjunction?

Answer 11

Crossvover too near/far from the centromere increase chromosome nondisjunction.

Distal exchanges are less effective in ensuring appropriate spindle attachment and separation of paired homologs in meiosis I

Proximal exchanges, or excessive number of exchanges, lead to entanglement of paired homologs in meiosis I => reductional division

Question 12

What is the maternal age effect?

Answer 12

The notable increase of aneuploidy in the eggs of women approaching menopause

Question 13

What is the “two hit” theory for the maternal age effect?

Answer 13

1st Hit = diminished recombination from lack of chiasma or mislocalization -> chromosome more susceptible to possible nondisjunction

2nd Hit = diminished ability of oocytes to successfully complete chromosome segregation in the presence of unfavorable recombination events

Question 14

What is the function of the cohesion complex in meiosis?

Answer 14

It ensures cohesion b/w sister chromatids and maintains inter-homolog associations distal to the site of crossovers

Degradation of cohesion complexes over the extended meiosis I-arrest (oocytes) results in precocious separation of homologs.

Question 15

What are the common clinical features of Trisomy 21?

Answer 15

(Down Syndrome)
Characteristic facies
Short stature
Hypotonia
Moderate intellectual disabilities

Endocardial cushion defects
Duodenal atresia and other GI anomalies
Hirschprung disease

Question 16

What are the common clinical features of Trisomy 18?

Answer 16

(Edwards Syndrome)
Intrauterine growth retardation
Characteristic Facies
Severe intellectual  disabilities 
Characteristic hand positioning

Valvular heart disease
Posterior fossa CNS maldevelopment
Diaphragmatic hernias
Renal anomalies

Question 17

What are the common clinical features of Trisomy 13?

Answer 17

(Patau Syndrome)
Characteristic facies
Sever intellectual disabilities

Holoprosencephaly
Facial clefts
Polydactyly
Renal anomalies

Question 18

What are the common clinical features of 47, XXY?

Answer 18

(Klinefelter Syndrome)
Tall stature,
Hypogonadism
Elevated frequency of gynecomastia
High frequency of sterility
Language impairment

Question 19

What are the common clinical features of 45, X?

Answer 19

(Turner Syndrome)
Short stature
Webbed neck
Edema of hands and feet
Broad shield-like chest
Narrow hips
Renal and cardiovascular anomalies
Gonadal dysgenesis (failure of ovarian maintenance)

Question 20

What is mosaicism?

Answer 20

The presence of at least two genetically different cells in a tissue, that is derived from a single zygote.

• Arises from mutations in single cells (prenatal or postnatal) generating clones of cells genetically different from the original zygote.
• Mosaic phenotypes are highly variable and the effects of mosaicism are very difficult to predict.

Question 21

What is germ-line mosaicism?

Answer 21

A result of a somatic mutation that occurs early in development and generates a mutt sub-population of germ cells.

• It is possible for a germ line mosaic individual to conceive multiple offspring with apparently new mutations
• Germ line mosaicism has been demonstrated in nearly every Mendelian and chromosomal disorder