11 - Intro to Cytogenomics Flashcards
Medical cytogenomics
- Studies gross human genome variation in health and disease
- Involves heredity at the cellular level
Human chromosomes
23 pairs (22 autosomes, 1 sex chromosome)
p arm
Short
q arm
Long
Methods for cytogenomic analysis
- Conventional cytogenetics
- Chromosomal microarray
- Fluorescence in situ hybridisation (FISH)
- Quantitative fluorescence PCR (QF-PCR)
- Genomic sequencing
Conventional genetics
- Requires dividing cells
- Resolution 5-10Mb
FISH
- Dividing/non dividing cells
- Resolution ~200Kb
Chromosomal microarray
- DNA based
- Resolution ~50Kb
QF-PCR
- DNA based
- Resolution single locus
Genomic sequencing
- DNA based
- Single nucleotide resolution
- Both sequence and structural info
Chromosome abnormalities
Deviations from the standard pattern of 23 pairs of chromosomes with known morphology (can be numerical or structural)
Numerical chromosome abnormalities
- Deviations in chromosome number (trisomy 21)
- Usually occur de novo (low recurrence risk)
Mechanism of numerical chromosome abnormalities
Cell division errors or fertilisation errors
Cell division errors
- Checkpoint defects
- Cohesion defects
- Centrosome amplification
- Microtubule defects
Fertilisation errors
Dispermy / trispermy
Euploid numerical abnormalities
Multiples of the haploid set (triploid, tetraploid)
Aneuploid numerical abnormalities
Gain or loss of one or a few chromosomes (trisomy 21, monosomy X)
Structural chromosome abnormalities
- Chromosomal breakage and reunion in a different configuration
- Can be balanced (no net gain or loss), or unbalanced (gain/loss of chromosomal material)
- May be inherited
Robertsonian translocations
- Translocation of chromosome 21 to chromosome 14 (45 chromosomes present)
- Risk for chromosomally abnormal offspring (translocation trisomy 21)
Metacentric
p arm = q arm
Submetacentric
p arm shorter than q arm
Acrocentric
Really short p arm with regular q arm
Balanced translocations
- Robertsonian translocation
- Reciprocal translocation
Paracentric
Inversion on one side of centromere
Pericentric
Inversion involving the centromere
Unbalanced structural abnormalities
- Deletion
- Duplication
- Interstitial deletion
- Sister chromatid recombination (isochromosome)
- Loss of borth termini (ring chromosome)
Mosaicism
Presence of cell lines with different chromosomal constitution in the same individual (numerical or structural changes)
Clinical impact of cytogenomic variants
- No apparent effect
- Reproductive issues
- Congentital anomalies
- Developmental issues
- Cancer
