2. Chromosomes (1) Flashcards
DNA is packaged into a structure called the _______. The chromosomes are found within the nucleus of the cell.
chromosome
Homologous chromosomes:
Set of one maternal and one paternal chromosome that pair up with each other inside a cell during cell division.
Sister chromatids:
Refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined by a common centromere.
Centromere:
Essential to the division of cells and ensure
the accurate segregation of chromosomes.
Telomeres:
A region of repetitive nucleotide sequences
at each end of a chromosome, which protects the end
of the chromosome from deterioration or from fusion
with neighbouring chromosomes.
Types of chromosomes
▣ Chromosomes are classified according to the position of the centromere: (4)
Visualization of the type of chromosomes:
What are the types of Cytogenetic tests? (5)
What is cytogenic test resolution?
What is the Karyotype? (4)
▣ A karyotype is an individual’s collection of
chromosomes
▣ It is the number and appearance of chromosomes in
the nucleus of a eukaryotic cell
▣ The term also refers to a laboratory technique that
produces an image of an individual’s chromosomes
▣ Involves the isolation, staining and visual examination
of chromosomes
What is the cell cycle?
Karyotype technique: (3)
How are karyotypes cultured? (3)
How are karyotypes harvested? (3)
How are karyotypes analysed? (3)
What are the types of staining? (3)
Metaphase spread vs Karyogram:
Karyotype resolution
▣ Total # of bands ______
▣ Depends on how _______ chromosomes
are- metaphase or prophase
▣ Generally 350-____
visible
condensed
550
What is the ISCN?
International Standard for Cytogenic Nomenclature
ISCN Abbreviations:
What is Fluorescent In-Situ Hybridization (FISH)? (2)
▣ Detects small deletions/duplications which are not
visible using conventional cytogenetic techniques
▣ Molecular cytogenetic method used to detect and
localize the presence or absence of specific DNA
sequences on chromosomes
FISH
▣ Need to know what you are looking for
▣ Utilizes ________ base pairing
▣ _______ bind to region of interest
complimentary
probes
FISH technique: (4)
What is the denaturing process of FISH? (3)
▣ To generate single stranded DNA
▣ Formamide and ethanol
▣ Heat- water bath or hotplate
What is the probing process of FISH? (2)
▣ Specifically designed short section of single-
stranded DNA
▣ Fluorescently labelled to enable visualisation
when bound
What is the hybridising process of FISH? (2)
▣ Binding (re-annealing) of probe and sample
single-stranded DNA
▣ Heat and humidity
What is the analysing process of FISH? (5)
▣ Visualise using fluorescent microscope
▣ Each hybridised probe is visualised as a
distinct signal
▣ Control- different colour fluorescence
▣ Analyse multiple cells
▣ Deletion <2 signals; duplication >2 signals
What are the uses of FISH? (3)
▣ Microdeletions and duplications
▣ Confirm rearrangements
▣ ID origin of material (ring chromosome/
satellite chromosome)
How are microdeletions visualised?
22q11 microdeletion:
1p36 duplication:
Translocation:
Marker chromosome:
Karyotype vs FISH: (7)
Normal somatic cell:
Diploid (46 chromosomes). Contains 2 haploid
chromosome sets.
Normal gamete:
Haploid (23 chromosomes)
Types of numerical abnormalities
Polyploidy: (2)
▣ More than 2 haploid chromosome sets
▣ Example: triploidy (3 haploid chromosome
sets = 69 chromosomes)
Types of numerical abnormalities
Aneuploidy: (3)
▣ Gain or loss of one (or more) chromosomes
▣ Example: trisomy (46 + 1 = 47 chromosomes)
▣ Example: monosomy (46 – 1 = 45 chromosomes)
▣ Normal female: 46, XX
▣ Normal male: 46, XY
▣ Triploidy female: 69, XXX
▣ Triploidy male:
▣ Trisomy:
▣ Monosomy:
▣ Mosaic:
▣ Triploidy male: 69, XXY or
69, XYY
▣ Trisomy: 47, XY, +21
▣ Monosomy: 45, XX, -21
▣ Mosaic: 46, XX/47, XX, +21
What does Non-disjunction during meiosis result in? (2)
▣ Non-disjunction in meiosis I
□ Two homologous chromosomes fail to
separate
□ Results in trisomic or nullisomic embryos
▣ Non-disjunction in meiosis II
□ Two sister chromatids don’t separate
□ Results in trisomic or nullisomic embryos
Mechanisms resulting in polyploidy
▣ Caused by fertilisation _________.
Abnormalities
▣ Digyny:
□ Diploid ovum (as a result of non-expulsion of the
second polar body, for example) is fertilised by a
haploid spermatozoa
▣ Diandry: (2)
□ Fertilisation of one oocyte by two spermatozoa
□ Four times more frequent than digyny
Abnormal fertilisation resulting in polyploidy:
What is Mosaicism? (2)
□ Occurs when there are two or more different cell
lines present
□ The different cell lines have different karyotypes
(chromosome arrangements)
What is Chimerism? (2)
□ Two or more cell lines present originating from two
or more zygotes
□ May arise from early fusion
What is Trisomy 21 (Down syndrome)? (3)
Clinical features of Down syndrome: (8)
▣ Characteristic dysmorphic features
▣ Intellectual delay
▣ Global developmental delay
▣ Hypotonia
▣ Congenital heart defects
▣ Hearing loss
▣ Vision problems, cataracts
▣ Hypothyroidism
What is Trisomy 13 (prev. Patau syndrome)?
What is Trisomy 13 (prev. Patau syndrome)?
What is Turner syndrome?
What is Klinefelter’s syndrome?
▣ A chromosome imbalance due to structural changes
within the chromosome, such as: (7)
□ Deletions
□ Duplications
□ Translocations
□ Inversions
□ Insertions
□ Ring chromosomes
□ Isochromosomes
▣ One chromosome can have multiple structural
abnormalities
▣ Usually, the total number of chromosomes is normal
▣ There is a change in their structure: (3)
□ Missing
□ Extra
□ Switched – in a different place
What is a deletion? (3)
▣ Part of the chromosome is missing or deleted
□ Terminal or interstitial deletion
▣ Some genetic material is missing
□ Can cause syndromic features
□ Depends on the genes involved in deletion
▣ Sporadic or dominant
□ If dominant: 50% recurrence risk
How can you test for a deletion? (4)
Test: FISH, Array, MLPA or karyotype
What are Interstitial and terminal deletions?
What are some syndromes associated with deletions? (3)
What is a duplication? (3)
▣ Part of the chromosome is duplicated
□ Terminal or interstitial duplication
□ Direct (tandem) or inverted
▣ Results in extra genetic material
□ Severity depends on the genes involved
□ Less severe than deletions
▣ Sporadic or inherited
□ If inherited: 50% recurrence risk
How can you test for duplications? (4)
Test: FISH, Array, MLPA or karyotype
What are interstitial and terminal duplications?
What are the syndromes associated with duplications?
What is a translocation: Reciprocal? (3)
▣ Exchange of material between chromosomes
▣ Balanced:
□ No loss or gain of genetic material
□ Individuals are usually phenotypically normal
▣ Unbalanced:
□ Gain or loss of genetic material – severity depends on size
□ Can be inherited from a balanced parent – recurrence is complicated
How do you test for a reciprocal translocation?
Array if unbalanced or karyotype if balanced
What is a Translocation: Robertsonian? (2)
How do you test for a robertsonian translocation?
Karyotype
Robertsonian vs reciprocal translocation:
What are Recurrent miscarriages?
What is an inversion? (3)
▣ Portion of a chromosome broke off, inverted and
reattached
▣ Pericentric or paracentric
▣ If isolated the individual is often phenotypically normal
□ Can be a ‘normal variant’
How do you test for an inversion?
Karyotype
What are the types of inversions? (2)
What is an Insertion? (3)
▣ Portion of a chromosome broke off and is inserted
elsewhere
▣ Interchromosomal or intrachromosomal
▣ Direct insertion or inverted insertion
How do you test for an insertion?
Karyotype
What is a ring chromosome? (5)
▣ Portion of a chromosome broke off and formed a ring
▣ Can happen with or without loss of genetic material
▣ Very rare
▣ Often severe
▣ Usually sporadic
How do you test for ring chromosomes?
Karyotype
What is an isochromosome? (2)
▣ Formed by a mirror image copy of a chromosome
segment
▣ Results in a gain and loss of genetic material
How do you test for isochromosomes? (4)
FISH, Array, MLPA or karyotype
What are some syndromes associated with isochromosomes?
