Compiled from lecture notes, this is a condense but detailed summary of human chromosomes and their analysis (cytogenetics) including cell cycle progression and non-disjunction covered in BHCS3009 module. All the information (and more) is available in one place in a logical order, easy to search an...
Human chromosomes and their analysis – cytogenetics
Cytogenetics – how chromosomes relate to cell behaviour, particularly during mitosis and meiosis
Early history of cytogenetics
• Arnold 1879 – described human cells in division
• Flemming 1882 – cell division in corneal epithelium
• Hauseman 1891 – chromosome counts of 18, 24 and >46
• De Winiwarter 1912 – 47 chr in spermatogonia cell, suggest XX/XO
• Painter 1921 – spermatogonia cell count range from 45-48, although in clearest plates only 46
chromosomes found
• Painter 1923 – concluded 48 correct chromosome number, idea persistence until 1956
• Painter 1924 – confirmed presence of X and Y
• Koller 1937 – presence of Y confirmed in spermatocytes
• Tijo and Levan 1956 – 46 chromosomes in cultured fibroblast cells
• Ford and Hamerton 1956 – 46 chromosomes in meiotic cells
• Lejeune 1956 – first association of chromosome abnormality (CA) with disease (Down Syndrome)
• Ford and Jacobs 1956 – role of Y in sex determination
• Moorhead 1960 – PHA stimulation of human lymphocytes to provide mitotic cells
• Howell and Hungerford 1960 – associated of CA with malignant disease (chronic myeloid
leukaemia)
• Caspersson 1971 – identification of individual chromosomes after staining with quinacrine (Q
banding)
• Yunis 1976 – high resolution banding and microdeletion
• 1990s – development of FISH and molecular cytogenetics
• 2005 – adoption of microarray CGH testing (identify microdeletion syndromes)
Incidence of chromosome abnormalities – Sankaranarayaran 1979
• 10% spermatozoa, 25% mature oocytes
• 50% spontaneous miscarriages
• 20% normal embryos (selective abortion)
• 5% still borne
• 1% live births
• Predates microdeletion syndromes
• Would expect 22x more autosomal Cas in live births than sex chr abnormalities as 22 autosomal chr
pairs and only 1 sex chr pair – not the case as most autosomal CAs not viable for life
Transmission of chromosomes
• Haploid sperm and eggs originate from diploid precursors by meiosis
• In fertilised egg, sperm and egg chr initially form from separate male and female pronuclei – these
combine during first mitosis of embryo
, Cell cycle
• Checkpoints and proliferation decision points monitor
progress of cell through cell cycle
• Interphase comprises of G1, S and G2
o Chromosomes contain 1 DNA double helix from
anaphase until DNA duplicated in S phase
o From S phase until end of mitosis, chromosome
consists of 2 chromatids, each containing a DNA
duplex – 2 DNA double helices per
chromosomes
• DNA content of a diploid cell before S phase is 2C (1 double helix), between S phase and mitosis is
4C (2 double helices)
• Individual chromosomes occupy distinct chromosome territories in the interphase nucleus – can
see with chromosome painting counterstained with DAPI
• Formation of metaphase chromosomes
o From DNA duplex
o Estimate packing ratios (degree of compaction of linear DNA duplex) are 1:6 for
nucleosomes, 1:36 for 30nm fibre, >1:10,000 for metaphase chromosome
• Mitosis
o Deconvolution microscopy with HeLA cells
o DNA stained with DAPI (falsely coloured red)
o Microtubules stained with beta-tubulin antibody (falsely coloured green)
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller AH1984. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £9.79. You're not tied to anything after your purchase.
