Principles of Clinical Cytogenetics

Question 1

Cytogenetics

Answer 1

Study of chromosomes, their structure, and inheritance

Question 2

Chromosome sources

Answer 2

Cell types- T lymphocytes, Chorionic Villi (located on border between maternal/fetal blood), Amniotic fluid.

Question 3

Chromosome Nomenclature

Answer 3

Regions named by arm counting from centromere outward (p1,p2–>q1,q2)
Bands: p11 or q12
Sub Bands: p11.1
Sub Sub Bands: p11.12

Question 4

Metacentric

Answer 4

centromere near central region of chromosome

Question 5

Submetacentric

Answer 5

Centromere is off center and arms are diff. lengths

Question 6

Acrocentric

Answer 6

Centromere near telomere (13,14,15,21 & 22)

Contains small masses of chromatin-satelites attached to their short arms (p) by stalks contain RNA

Question 7

Telocentric

Answer 7

Centromere @ one end & has only one arm (not found in humans)

Question 8

Giemsa Banding/G Banding

Answer 8

Most common method, Chromosomes from Prometaphase/metaphase, Produces Light & Dark bands

Question 9

Q Banding

Answer 9

Staining with quinacrine mustard
Bright Q bands correspond to Dark G bands
Useful in detecting hetreomorphisms

Question 10

R Banding

Answer 10

Heat Chromosomes b4 staining

Better for observing regions that stain poorly

Question 11

T Banding

Answer 11

ID subset of R bands at Telomeres

Heat treatment, G Banding, Dyes

Question 12

C Banding

Answer 12

Staining Centromeric regions & other regions with Constitutive heterochromatin (highly condensed & repetitive DNA)

Question 13

High Res Banding

Answer 13

G or R banding of chromosomes from Prophase/prometaphase

Question 14

FISH (Fluorescence In Situ Hybridization)

Answer 14

Uses DNA probes for details
Chromosomal “painting” (probe entire arm)
Can probe for several targets= spectral karyotyping

Question 15

Abnormalities of chromosome #

Answer 15

Euploidy= Multiple of 23
Heteroploidy = Any chromosome compliment other than 46 (ex. Triploid/Tetraploid)

Question 16

Abnormalities of chromosome #

Answer 16

Triploid- Fertilization by 2 sperms & 1 egg= Parietal hydatidform moles–>extra parental chromosomes= abnormal placenta

Tetraploid- Failure of completion of an early cleavage of zygote

Question 17

Abnormalities of chromosome #

Answer 17

Aneuploidy: A cell not a multiple of 23 RESULTS from meiotic nondisjunction.
ie-
Monosomy- autosomal cell 1 copy=lethal
Trisomy- 3 copies of chromosomes. Viable for life if it is located @ (21,18,13)

Question 18

NONdisjunction

Answer 18

Failure for pair of chromosomes to disjoin during one of 2 meiotic divisions

During meiosis = MOSAICISM

Question 19

Abnormalities of chromosome structure

Answer 19

Results from chromosome breakage followed by being put back together in abnormal combo.
Balanced/Unbalanced (addition/missing)

Question 20

Stable/Balanced rearrangements

Answer 20

capable of passing through cell division
requires normal structure of chromosome (centromere/telomeres)

Likely to produce unbalanced gametes

Inversions-Pericentric NOT involving centromere/Pericentric Involving centromere
Most common (inv(9)(p11q12)-no effects

Question 21

Balanced rearrangements/Translocations

Answer 21

Exchange of chromosome segments between not same chromosomes
Reciprocal: Break into 2 different chromosomes-material exchanged
Robertsonian: Long arms (q) of 2 non-same acrocentic (no centromere) chromo. fuse @ centromere–>fusing into 1 NO short arm (p)
Clinical-Carriers of translocation @ 21 can produce child with downs

Question 22

Unbalanced rearrangements/Duplications

Answer 22

Results in partial trisomy

From un = crossing over

Question 23

Unbalanced rearrangements/Ring chromosomes

Answer 23

Small un ID chromosomes
Seen in Chrom 15 and Sex chromosomes
Without telomeres & unstable

Question 24

Unbalanced rearrangements/Isochromosome

Answer 24

Where one arm is missing and mirror image is duplicated (most common is long arm q)

Question 25

Unbalanced rearrangements/Deletions

Answer 25

Caused by: Chromosomal breakage & loss of Acentric element (lacks centromere)
Un = crossing over

Question 26

Mosaicism

Answer 26

2 or more chromosomes complements present-numerical most common

Question 27

Genomic imprinting

Answer 27

Diff. in gene expression from alleles inherited from father & mother
ONLY one allele expressed maternal/paternal

Question 28

Chromosomes in down syndrome

Answer 28

Trisomy @ 21 due to Meiotic disjunction (improper sep. of sister chromatids @ anaphase)21q21q Translocation=Isochromosome–> canNOT have normal children

Question 29

Pseudoautosomal region

Answer 29

Location where X/Y chromosomes pair up @ meiosis 1

Question 30

Embryology of Repro. System

Answer 30

-6th week of development-Presence of Y-linked gene called TDF (testis determining factor) made from Leydig cells-produce testosterone.-Male genitalia develops under influence of androgens & female does NOT

Question 31

Y chromosome

Answer 31

-TDF/SRY sex determining region-SRY encode for transcription factor, implicated in male determination-AZF (Azoospermia factors):deletion can lead to infertility

Question 32

Barr Body

Answer 32

-Inactive X chromosome-Males/females have 1 active X chromosome-ex. 47xxy & 48xxyy= 1 barr body