Chromosomal Abnormalities Flashcards
Karyotype defination?
Individual collection of chromosomes
Also refers to lab technique to produce an image of it
Method of making a karyotype?
5ml heparinised venous blood Isolate w.b.c culture with phytohaemagglutinin 48 hours later add colchicine place in hypotonic saline place on slide fix and Gisema stains (nucleic acid stain)
What does Heparin do?
Stops Coagulating
What does phytohaemagglutinin do?
(PHA) Stimulates T-lymphocyte growth bye mitotic stimulation
What does colchicrine do?
The effect of colchicine, which inhibits microtubule polymerization and thus assembly of the mitotic spindle, demonstrates the presence of another checkpoint in the cell cycle. When colchicine is added to cultured cells, the cells enter mitosis and arrest with condensed chromosomes.
What are Ideogram?
Ideograms are diagrammatic or idealized representations of chromosomes, showing their relative size, homologous groups and cytogenetic landmarks.
What is the P-arm and Q-arm
Petite arm, long arm. connected at centromere.
What are band number?
Chromosome banding refers to alternating light and dark regions along the length of a chromosome, produced after staining with a dye
due to new techniques, have sub-bands.
Nomenclature example : 3p21 - Chromosome 3, petite arm, band 2, sub band 1
What is bphs?
bands per haploid set
dark bands (heterochromatin) -fewer compact genes light bands (euchromatin) more open genes
What is Aneuploidy?
Abnormal number of chromosomes
Non Disjuncture can result in ?
Trisomy or Monosomy
Pseudo-autosomal region
region which does not get inactivated during X chromosomal inactivation, (is on both y and x chromosome)
Trisomy 21
Risk of maternal non-disjunction increases w/age e.g. trisomy 21 (Down’s syndrome)
Can see 3 chromosome 21s in karyotype
Can see amounts of DNA as well using QF-PCR (quantitative fluorescence PCR)
Oogenesis and female disjunction
Most aneuploidy caused by non-disjunction arises in oogenesis. likely due to degradation of factors which hold homologous chromatids together
Paternal affect on anueploidy?
Affect single gene disorders by point mutation sin FGFR2, FGFR3, RET
Apert syndrome
Crousen syndrome
Pfeiffer syndrome
Single chromosome abnormalities
(during crossing over) Deletion, duplication, most caused by unequal cross overs
paracentric inversion: inverted segment in single chromosome
pericentric inversion: inverted segment at centromere
–> carriers often unaffected but can cause reproductive problems
What is selfish spermatogonial selection?
Mutated spermatogonia undergo favoured mitosis in comparison to neighbouring wild type cells. Paternal age is not a risk factor for increased aneuploidy like oogenesis is but spermatocytes may accumulate defects over time.
Two chromosome abnormalities
If both chromosomes remain balanced the carrier will not have problems but may cause problems in off spring.
Can cause partial trisomy or monosomy.
Chromosomal deletion examples?
Cri-du-chat syndrome 46,XY,del(5p)
Can be detected easily by microscope
Microdeletion in chromosomes?
Seen in high resolution banding, molecular genetics
20+ genes deleted
Velocardiofacial/DiGeorge syndrome 22q11.2 del
Williams Syndrome 7q11.23 deletion Phenotype?
(lacking elastin gene) Long philtrum Short upturned nose arches eyebrows absence of social anxiety
If abnormality too small to be seen on karyotype? E.g. Williams syndrome deletion
Targeted FISH
Fluorescent in situ hybridisation
Duplication Syndrome 7q11.23 Phenotype
Delayed speech development, autistic behaviours, dilation or aorta, flat eyebrows, broad nose and short philtrum.
Duplication usually have a milder phenotype than reciprocal deletion of same gene
What are Metacentric chromosomes?
centromere is in middle, meaning p and q arms are of comparable length
What are Submetacentric Chromosomes?
centromere off-centre, leading to shorter p arm relative to q arm
What are Acrocentric Chromosomes?
centromere severely off-set from centre, leading to much shorter p arm. Has Stalk and Satellite at top of P arm
What is Robertsonian translocation?
Occurs between acrocentric chromosomes Common: 13 + 14 , 14 + 15, 14 + 21
Unaffected people - can have balanced genotypes, problems in offspring
What is Mosaicism?
Presence of 2+ populations of cells with different genotypes caused by X-inactivation
What are the 2 mechanisms of Mosaicism?
Non-disjuncture during early development
Loss of extra chromosome in early development (this can also turn lethal aneuploidy survivable with less severe phenotype)
