Principles of Clinical Cytogenetics Flashcards
Cytogenetics
Study of chromosomes, their structure, and inheritance
Chromosome sources
Cell types- T lymphocytes, Chorionic Villi (located on border between maternal/fetal blood), Amniotic fluid.
Chromosome Nomenclature
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
Metacentric
centromere near central region of chromosome
Submetacentric
Centromere is off center and arms are diff. lengths
Acrocentric
Centromere near telomere (13,14,15,21 & 22)
Contains small masses of chromatin-satelites attached to their short arms (p) by stalks contain RNA
Telocentric
Centromere @ one end & has only one arm (not found in humans)
Giemsa Banding/G Banding
Most common method, Chromosomes from Prometaphase/metaphase, Produces Light & Dark bands
Q Banding
Staining with quinacrine mustard
Bright Q bands correspond to Dark G bands
Useful in detecting hetreomorphisms
R Banding
Heat Chromosomes b4 staining
Better for observing regions that stain poorly
T Banding
ID subset of R bands at Telomeres
Heat treatment, G Banding, Dyes
C Banding
Staining Centromeric regions & other regions with Constitutive heterochromatin (highly condensed & repetitive DNA)
High Res Banding
G or R banding of chromosomes from Prophase/prometaphase
FISH (Fluorescence In Situ Hybridization)
Uses DNA probes for details
Chromosomal “painting” (probe entire arm)
Can probe for several targets= spectral karyotyping
Abnormalities of chromosome #
Euploidy= Multiple of 23 Heteroploidy = Any chromosome compliment other than 46 (ex. Triploid/Tetraploid)
Abnormalities of chromosome #
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
Abnormalities of chromosome #
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)
NONdisjunction
Failure for pair of chromosomes to disjoin during one of 2 meiotic divisions
During meiosis = MOSAICISM
Abnormalities of chromosome structure
Results from chromosome breakage followed by being put back together in abnormal combo.
Balanced/Unbalanced (addition/missing)
Stable/Balanced rearrangements
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
Balanced rearrangements/Translocations
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
Unbalanced rearrangements/Duplications
Results in partial trisomy
From un = crossing over
Unbalanced rearrangements/Ring chromosomes
Small un ID chromosomes
Seen in Chrom 15 and Sex chromosomes
Without telomeres & unstable
Unbalanced rearrangements/Isochromosome
Where one arm is missing and mirror image is duplicated (most common is long arm q)
