Cytogenetics

Question 1

Acquired chromosome abnormality

Answer 1

An example of this would be abnormalities present in malignant cells of an individual but not normal cells.

Question 2

Metacentric

Answer 2

Centromere near the middle of a chromosome.

Question 3

Submetacentric

Answer 3

Centromere visible off center creating a short (p) and long (q) arm.

Question 4

Acrocentric

Answer 4

Centromere very near one end.

Question 5

Giemsa (G)-banding

Answer 5

The most widely used technique for human chromosome identification in clinical cytogenetics laboratories today. Chromosomes are treated with dilute trypsin followed by the staining with Giemsa. In extension to this, techniques now can obtain longer, less condensed prometaphase chromosomes which exhibit twice as many G-bands (800) as the metaphase chromosomes preparations (400).

Question 6

Karyotype

Answer 6

Display of chromosome pairs according to their size and group

Question 7

Ideogram

Answer 7

Schematic representation of chromosomes with their banding pattern.

Question 8

Cytogenetic Nomenclature

Answer 8

Total chromosomes, sex chromosome constitution, Abnormality.

47 XX +21

Question 9

Fluorescence In Situ Hybridization (FISH)

Answer 9

Hybridization in situ of labeled, single-stranded DNA probes to denatured DNA in otherwise standard chromosome spreads. Useful for microdeletion syndromes. A DNA probe of known chromosomal location can be used in a FISH assay to detect subtle chromosomal rearrangements involving that locus, which are undetectable by banding. Chromosomal painting is useful in identification of inter-chromosomal rearrangements. Dividing cells are not always necessary for use, as alpha-satellite probes hybridize to corresponding highly repetitive sequences at the centromeric region of particular chromosomes and permit rapid determination of the copy number of the chromosome in large number of dividing or interphase nuclei. Identification of trisomies or monosomies.

Question 10

Alphoid Repeats

Answer 10

A type of FISH probe used for chromosome specific, centromeric repeat sequences. They produce intense, tight signals and are useful for interphase FISH.

Question 11

Numerical chromosomal abnormality

Answer 11

Changes in chromosomal number

Question 12

Structural chromosomal abnomality

Answer 12

Rearrangements of chromosomes such as missing a piece.

Question 13

Euploidy

Answer 13

Cells containing a multiple of 23 chromosomes ie triploidy, tetraploidy.

Question 14

Aneuploidy

Answer 14

Cells do not contain a multiple of 23 chromosomes usually having an extra single chromosome (trisomy) or a missing chromosome (monosomy).

Question 15

Trisomy 21- Down Syndrome

Answer 15

1/800 live births and most common cause of moderate mental retardation. Clinical features include hypotonia, characteristic facial features, minor abnormalities, congenital heart disease, duodenal atresia, mental retardation. Most commonly from a nondisjunction in meiosis I associated with advanced maternal age. Robertsonian translocation is the second most common form and it is caused by a fusion of the long arms of two acrocentric chromosomes with loss of both short arms. The children of this individual is at risk for a chromosomal abnormality. Mosaicism is the third cause and results in a non disjunction of post zygotic mitotic cells, resulting in some normal and some disease.

Question 16

Edward’s Syndrome

Answer 16

Trisomy 18

Question 17

Patau Syndrome

Answer 17

Trisomy 13

Question 18

Trisomies and Advanced Maternal Age

Answer 18

Increase in non-disjunction in older females.

Question 19

Triploidy

Answer 19

Rare; mostly miscarriages. Paternally derived extra chromosomal set.

Question 20

Balanced Abnomality

Answer 20

Rearrangement does not produce a loss or gain of material. Usually no phenotypic effect. Risk for unbalanced gametes. Example is translocation.

Question 21

Unbalanced Abnomality

Answer 21

Rearrangement causes loss or gain of chromosomal material. Severe phenotypic effect. Example is deletions.

Question 22

Robertsonian translocation

Answer 22

Confined to acrocentric chromosomes 13, 14, 15, 21, 22. The long arms are fused at centromeres with loss of short arms.

Question 23

Reciprocal translocation

Answer 23

Breakage of nonhomologous chromosomes with reciprocal exchange of chromosome material. Carriers are normal but risk abnormal offspring.

Question 24

Terminal Deletions

Answer 24

Single break leading to loss of chromosome material distal to the breakpoint.

Question 25

Interstitial Deletions

Answer 25

Two breaks with loss of genetic material in between.

Question 26

Cri du chat syndrome

Answer 26

Terminal deletion of 5p. de novo terminal deletion, offspring of a balanced carrier.

Question 27

Velocardiofacial Syndrome

Answer 27

Deletion 22q11.2

Question 28

Array Based Comparative Genomic Hybridization (array-CGH)

Answer 28

Detects small chromosomal deletions and duplications. Detects all known microdeletion and microduplication syndromes.

Question 29

Turner Syndrome

Answer 29

1/500 female births. 45,X lost paternally. Short, gonadal dysgenesis, lack of secondary sex, amenorrhea, infertiliy, minor abnormalities to face and extremities, lymphedema, congenital heart disease, renal abnormalities, difficulties with spacial perception. 45,X karyotype, structural abnomality in one of the two chromosomes such as deletion in p or q or an isochromosome for the long arm.

Question 30

Klinefelter Syndrome

Answer 30

Most XXY, some mosaic.

Question 31

XXX

Answer 31

Maternal nondisjunction with advanced maternal age.

Question 32

XYY

Answer 32

Not from maternal disjunction and no increase in incidence with maternal age.

Question 33

Pseudoautosomal Region

Answer 33

Distal tips of the male and female sex chromosomes that can pair up and exchange genes.

Question 34

XX Male

Answer 34

XX contains some DNA specific to Y. SRY is the sex determining gene, located just below the pseudoautosomal region.

Question 35

Indications for Chromosomal Analysis

Answer 35

1. Multiple congenital malformations, mental retardation, growth failure
2. Suspected chromosomal abnormality
3. Couples with multiple pregnancy loss
4. Female with short stature or primary amenorrhea
5. Male with infertility
6. Ambiguos genetalia
7. Patient’s with hematological malignancies

Question 36

Constitutional Chromosome Abnomality

Answer 36

Chromosome Make-Up at birth