Numerical Chromosomal Abnormalities II

Question 1

Aneuploidy is

Answer 1

the condition in which cells contain an abnormal chromosome number

Question 2

Aneuploidy is frequently the result of __________

Answer 2

chromosome nondisjunction

Question 3

chromosome nondisjunction

Answer 3

the missegregation of chromosomes at metaphase in either mitosis or meiosis, such that daughter cells receive extra or fewer than the normal number of chromosomes

Question 4

Monosomy

Answer 4

the condition in which a cell lacks one copy of a chromosome

Question 5

Trisomy

Answer 5

the situation in which an extra copy of an entire chromosome is present in the cell

Question 6

Autosomal monosomies result in __________, although individuals that are monosomic for the __________ (45,X; Turner syndrome) survive

Answer 6

early embryonic lethality

X chromosome

Question 7

most __________ are compatible with at least some fetal development, but often result in spontaneous abortion

Answer 7

trisomies

Question 8

__________ errors in the first meiotic division predominate among almost all trisomies

Answer 8

maternal

Question 9

__________, is thought to be a significant risk factor for most, if not all, trisomies

Answer 9

increasing maternal age, (or more exactly, the proximity to menopause)

Question 10

Down syndrome

Answer 10

(trisomy 21) is the most common human chromosomal disorder ascertained in liveborn infants (~1/900). In more than 95% of trisomy 21 cases, the additional chromosome 21 is maternal in origin, and dosage studies indicate that nondisjunction during maternal meiosis I is by far the most common cause

Question 11

Nondisjunction events are related to

Answer 11

1. the positioning of chiasmata; crossover events that occur too near or too far from the centromere increase chromosome nondisjunction. Centromere-distal exchanges are less effective in ensuring appropriate spindle attachment and separation of paired homologs in meiosis I
2. the frequency of crossover events. The reduction or absence of recombination events increases the likelihood of nondisjunction

Question 12

Maternal Age Effect (2 models)

Answer 12

1. “two-hit” theory = diminished recombination +unfavorable recombination events
2. degradation of cohesin complexes over the course of the extended meiosis I arrest in oocytes results in precocious separation of homologs

Question 13

Trisomy 21

Answer 13

Down syndrome

• Characteristic facies, short stature, hypotonia, moderate intellectual disabilities
• Congenital malformations – endocardial cushion defects, duodenal atresia and other gastrointestinal anomalies, Hirschprung disease

Question 14

Trisomy 18

Answer 14

Edwards syndrome

• Intrauterine growth retardation, characteristic facies, severe intellectual disabilities, characteristic hand positioning.
• Congenital malformations – valvular heart disease, posterior fossa CNS maldevelopment, diaphragmatic hernias, renal anomalies

Question 15

Trisomy 13

Answer 15

Patau syndrome

• Characteristic facies, severe intellectual disabilities
• Congenital malformations – holoprosencephaly, facial clefts, polydactyly, renal anomalies

Question 16

XXY

Answer 16

Klinefelter syndrome

-Tall stature, hypogonadism, elevated frequency of gynecomastia, high frequency of sterility, language impairment

Question 17

X

Answer 17

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 18

Mosaicism

Answer 18

-the presence of at least two genetically different cells in a tissue that is derived from a single zygote

Question 19

Mosiacism results from

Answer 19

mutations arising in single cells in either prenatal or postnatal life, generating clones of cells genetically different from the original zygote

Question 20

Examples of how mosaic phenotypes are highly variable and the effects of mosaicism are very difficult to predict. (3)

Answer 20

A) Somatic chromosomal errors that occur during development lead to chromosomal mosaicism. Examples: 47,XX +21/46,XX (mosaic Down syndrome); 46, XX/46,XY (true hermaphroditism)
B) Somatic chromosomal mutation is a common mechanism through which cell lines come to overexpress oncogenes or lose tumor suppressor genes.
C) Mosaic parents with mild phenotypes can have fully affected offspring

Question 21

Germ line mosaicism exists when

Answer 21

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

Question 22

Human female and male germ line cells undergo approximately 30 or 50 mitotic cell divisions, respectively, before differentiating into stem germ cells that then enter meiosis. A __________ individual is therefore capable of conceiving multiple offspring with apparent __________ mutations

Answer 22

germ line mosaic

new (de novo)