chromosome abnormalities Flashcards
which tissue types can be cultured (5)
blood - T lymphocytes
skin/umbilical cord/placenta
bone marrow
solid tumour
amniotic fluid/chorionic villus
how do you prepare a cell culture
take a sample eg blood
add to culture medium + PHA
incubate at 37 C for 48-72 hours
add colcemid
add hypotonic solution
fix cells
cells spread onto slide by dropping
staining
banding
karyotyping
what is the system for naming chromosomes
ISCN
International System of Chromosome Nomenclature
eg 46 XX
what are the 2 types of chromosome abnormalities
1)numerical - very few that survuve birth
2)structural
what are the 3 types of numerical chromosome abnormalities
triosmy - 47,XX+21
monosomy - 45 X
polyploidy - 69, XXY
what are the 4 types of structural chromosome abnormalities
translocation
inversion
duplication
deletions
what is the frequency of chromosome abnormalities overall
1 in 200
what causes down syndrome
extra chromosome 21
triosmy 21
what causes edwards syndrome
extra chromosome 18
triosmy 18
examples of sex chromosome abnormalities
47, XXY Klinefelter
47, XXX Triple X
47, XYY
48, XXYY or 48,XXXY
what is triploidy
when there are three copies of every chromosome instead of the normal two
what causes patau syndrome
extra chromosome 13
what is reciprocal translocation
structural chromosome abnormality
occur when part of one chromosome is exchanged with another
what is alternate segregate translocation
when two normal non-homologous chromosomes and two translocated chromosomes separate into different poles.
what is robertsonian translocation
when effectively, the whole of a chromosome is joined end to end with another. This type of translocation involves only chromosomes 13, 14, 15, 21 and 22, because the ends of their short arms have similar repetitive DNA sequences that predispose to their fusion.
what is Cri Du Chat syndrome
a chromosomal condition that results when a piece of chromosome 5 is missing
what causes prader villi and angelman syndrome
both caused by the absence of a limited region of chromosome 15, but differ with respect to the parental origin of the chromosome 15 present
what does FISH stand for
fluorescence in situ hybridisation
how does FISH work
use DNA probes labelled with fluorophores
they are hybridised directly to the chromosome preparation or interphase nuclei
define cytogenetics
refers to the study of tissue, blood, blood marrow, or culture cells in a laboratory, using banding or manipulating techniques to look for changes in the chromosomes, including broken, missing, rearranged, or extra chromosomes. Changes in the chromosomes may be a sign of a genetic disease or condition
how is FISH used in cytogenetics (4)
- can count chromosomes in interphase nuclei
- can look for submicroscopic deletions using locus-specific probes
- can interpret abnormalities more clearly
- can look for specific rearrangements such as gene fusion etc in acquired abnormalities
what is a microarray
a laboratory tool used to detect the expression of thousands of genes at the same time. DNA microarrays are microscope slides that are printed with thousands of tiny spots in defined positions, with each spot containing a known DNA sequence or gene.
improves resolution for detection of cytogenetic abnormaities
what is G band resolution on microarrays
5-10mb
what are constitutional chromosome abnormalities
- occur at gametogenesis
- affect all cells of the body
- heritable
what are acquired chromosome abnormalities
- changes occur during lifetime
- restricted to malignant tissue
- not heritable
what is the role of cytogenetics (4)
- confirmation of malignancy
- classification of a disease type
- prognosis
- monitoring
what are fusion/hybrid genes
breakpoints occur within the 2 genes involved
fusion creates a hybrid gene which gives rise to a chimaeric protein
what is deregulation
changes in gene expression modify cell behaviour and impair the normal functioning of tissues and organs.
can result in increased transcription and neoplastic growth
why are arrays better than microscopy when looking at genome
higher resolution
why is FISH useful
can provide quick results without the need to look at chromosomes
