Chromosomal abnormalities (21) Flashcards
What is the normal human karyotype?
- normal human karyotypes contain 22 pairs of autosomal chromosomes
- and one pair of sex chromosomes (allosomes)
- normal karyotypes for females contain two X chromosomes and are denoted 46,XX; males have both an X and a Y chromosome denoted 46,XY
At what stage of division can chromosomes be karyotyped?
metaphase
How do we show a translocation in cytogenetic nomenclature?
46, XX, t(5;10)(q34.1;q11.2)
means translocation between - chromosomes 5 and 10
- break points shown in 2nd brackets
How do we show a deletion in cytogenetic nomenclature?
46, XX, del(5)(q21q23)
- missing between bands q21 and q23 in chromosome 5
What is the purpose of mitosis?
- to create two identical daughter cells
- for growth and repair
- to replace exhausted cells
- 2n–> 2n
What is added to cultures in order to arrest cells in metaphase?
colcemid
What is the purpose of meiosis?
- to achieve reduction from diploid (2n=46) to haploid (n=23)
- to ensure genetic variation in the gametes
- enables random assortment of homologues and recombination
What is non-disjunction at meiosis 1?
chromosomes haven’t separated, so both chromosomes have gone to 1 daughter cell
so 2 trisomy and 2 monosomy zygotes
What is non-disjunction at meiosis 2?
1st division is normal, so each cell has 1 chromosome each, each containing 2 chromatids- but in 2nd division, sister chromatids fail to separate–> causes 2 normal gametes and 1 w/ trisomy, 1 w/monosomy
Why is female meiosis more vulnerable? (most aneuploidy is caused by non-disjunction in oogenesis)
- paused in utero until puberty
- 1 primary oocyte yields only 1 ovum bc polar bodies
- finite number of primary oocytes
How can we detect chromosomal aneuploidy prenatally?
Quantitative Fluorescence (QF-PCR)
Why is sex chromosome imbalance tolerated?
- X-inactivation of excess X chromosomes (e.g. XXX is not that bad bc only 1 X is active)
- very low gene content on Y chromosome (so XYY is often unnoticed)
Why is there an increased genetic risk associated with advanced maternal age?
over time the chromosomes in the egg are less likely to divide properly leading to the egg having an extra or missing chromosome
What technology do we use now to detect chromosomal copy number changes instead of karyotyping?
Array Comparative Genome Hybridisation (aCGH)
- test DNA in red
- reference DNA in green
- hybridise together
- look for regions of yellow, red and green… yellow means equal
What is a contiguous gene syndrome?
a clinical phenotype caused by a chromosomal abnormality- deletion or duplication- that removes several genes lying in close proximity to one another on the chromosome
What is the vulnerability of male meiosis?
- primary spermatocytes undergo around 23 mitotic divisions per year–> and potentially accumulate defects
- no equivalent to menopausal limit on reproductive span
How many chromatids are in each chromosome at metaphase?
each chromosome comprises 2 chromatids
4n prior to cell division
What features are shown on ideograms?
- ends are capped w/ a telomere to stop unravelling
- centromere (if in middle, metacentric)
- p-arm= small arm
- q-arm= long
- G-dark bands where DNA tightly bound, less accessible, gene-poor
- vs. G-light bands- more accessible
- Giesma staining
How do we show a monosomy (loss) in cytogenetic nomenclature?
45,XX,-7
missing chromosome 7
How do we show a trisomy in cytogenetic nomenclature?
47,XX,+8
How do we show an inversion in cytogenetic nomenclature?
46,XX,inv(3)(q21q26)
What is haploinsufficiency?
you need expression from both alleles to get a normal phenotype
What is imprinting?
methylation pattern that passes in germline of parent and are maintained during divisions
What is haplosufficiency?
only need expression from 1 of the alleles
