Lecture 1 - Clinical Cytogenetics

Question 1

Karyotype

Answer 1

display of chromosomes ordered by their length

Question 2

Haploid

Answer 2

having one copy of each chromosome (N = 1); e.g. human gamete

Question 3

Diploid

Answer 3

having two copies of each chromosome (N = 2); e.g. human somatic cell

Question 4

Aneuploid

Answer 4

having one or more extra or missing chromosomes

Question 5

Balanced chromosomal abnormality

Answer 5

no net gain or loss of chromosomal material

Question 6

Unbalanced chromosomal abnormality

Answer 6

net gain or loss of chromosomal material

Question 7

Uniparental disomy

Answer 7

a chromosome pair is derived solely from one parent in the diploid offspring

Question 8

p and q arms of chromosomes

Answer 8

short and long arms, respectively

Question 9

Metacentric chromosome

Answer 9

both arms are approximately equal in length

Question 10

Submetacentric chromosome

Answer 10

one arm is somewhat shorter than the other

Question 11

Acrocentric chromosome

Answer 11

one arm is much shorter than the other

Question 12

Autosome

Answer 12

any of the chromosomes other than the sex-determining chromosomes. In humans, X
and Y are the sex chromosomes

Question 13

Euchromatin

Answer 13

decondensed (active) form of a chromosomal region

Question 14

Heterochromatin

Answer 14

condensed (inactive) form of a chromosomal region. Constitutive heterochromatin is always condensed while facultative heterochromatin can become decondensed (active form) in certain circumstances

Question 15

Chromosome banding

Answer 15

staining of bands, or chromosome segments, allowing the precise
identification of individual chromosomes or parts of chromosomes

Question 16

Nondisjunction

Answer 16

the failure of the paired chromosomes to segregate properly during meiosis or
mitosis, resulting in daughter cells with abnormal numbers of chromosomes

Question 17

Reciprocal translocation

Answer 17

segments from two different chromosomes have been exchanged

Question 18

Robertsonian translocation

Answer 18

joining of two acrocentric chromosomes at the centromeres with loss
of their short arms to form a single abnormal chromosome

Question 19

Inversion

Answer 19

A segment of the chromosome is flipped around and the genetic material is inverted

Question 20

Ring chromosomes

Answer 20

usually occur when a chromosome breaks in two places and the ends of the
chromosome arms fuse together to form a circular structure

Question 21

Meiosis

Answer 21

type of cell division by which germ cells are produced. It results in a 50%
reduction in the number of chromosomes present in gamete-producing cells.

Question 22

Mitosis

Answer 22

type of cell division resulting in two cells with same number of chromosomes as
the parent cell

Question 23

Gametogenesis

Answer 23

Responsible for the concept that there are more rounds of DNA replication during the generation of male relative to female gametes

Question 24

Methods in clinical cytogenetics

Answer 24

Fluorescent in situ hybridization (FISH) allows distinct DNA segments >40-kb in length to be visualized on chromosome spreads. Spectral karyotyping (SKY) involves labeling each chromosome with a different dye combination, which allows one to track each chromosome on chromosome spreads. This is especially important for cells with abnormal karyotypes, see slide 23. Unlike SKY and FISH, array comparative hybridization (array CGH) does not require living cells. Genomic DNA of interest is labeled with fluorescent dyes and hybridized to slides that have short DNA probes attached to them. These DNA probes can represent virtually all or distinct areas of the genome. Based on the pattern of hybridization of the labeled genomic DNA to the
microarray, it is possible to identify insertions and deletions in the genome. The array CGH
method is becoming widely used in clinical cytogenetics laboratories.

Question 25

Congenital chromosomal disorders

Answer 25

Abnormal chromosome number in the

developing fetus is commonly associated with miscarriages.

Question 26

Nondisjunction

Answer 26

Nondisjunction can occur during meiosis I or
meiosis II and result in gametes with abnormal
chromosome number. This is an important
slide (slide 30) since it depicts the mechanism
responsible for a significant number of human
diseases associated with abnormal
chromosome number.

Question 27

Genetic mosaicism

Answer 27

In such cases, not all of a person’s cells have the same genetic makeup. This can involve single base mutations or chromosomal abnormalities. I
provided an example of genetic mosaicism due to mitotic nondisjunction early in development. In principle, genetic mosaicism could result in a milder form of disease.

Question 28

Autosomal deletion syndromes

Answer 28

A very large chromosomal segment tens of
megabases (Mb) in size, such as an entire arm, is deleted. Typically, this is due to a ‘de
novo’ mutation in the gamete of a parent or a mitotic error early in development.
Haploinsufficiency: the remaining copy of the gene is insufficient for normal health.

Question 29

Cri du chat syndrome

Answer 29

Patients have a deletion of the short arm of
chromosome 5. Although known as a mental retardation syndrome, patients have distinct
facial features and other symptoms such as hypotonia, poor muscle tone.

Question 30

Contiguous gene deletion syndromes

Answer 30

Associated with a small deleted genomic region containing two or more contiguous (located next to one another) genes. Itinvolves a maximum of a few megabases (Mb). The deleted genomic region tends to be much smaller than that of an autosomal deletion syndrome. Again, think about the possible roles of de novo mutations and haploinsufficiency in disease.

Question 31

Smith-Magenis syndrome (SMS)

Answer 31

Patients have deletions in the chromosome 17p11.2 genomic region. SMS affects multiple systems and patients show characteristic craniofacial abnormalities, learning disability, compromised kidney and heart function, and variable hearing and vision loss.

Question 32

DiGeorge syndrome

Answer 32

Patients have deletions in the chromosome 22q11.2 genomic region. Patients show cleft palate, heart defects, possible learning disability, lowblood calcium levels (hypocalcemia), and immune deficiency.