CHROMOSOME ABNORMALITIES AND GENE REARRANGEMENTS
Chromosome Rearrangements: recurrent miscarriage and infertility
ROBERTSONIAN TRANSLOCATIONS
Fusion of two acrocentric chromosomes (13,14,15,21,22) - it is these chromosomes because they have short p arms, containing highly repetitive DNA and no protein coding genes, so deletion of this short arm of the chromosome does not have a harmful effect on human development and health.
1/1000 prevalence
der(13;14) der(14;21) are most common
balanced carriers are phenotypically normal, but have reproductive risks
It is written down as der(13;14) for example, which means, the derivative of the fusion of chromosome 13 and 14.
RECIPROCAL TRANSLOCATIONS
Between any segments of any non-homologous chromsomes
1/500
Almost always unique to the family, only 46,XX,t(11;22) is recurrent
Balanced carriers are phenotypically normal, but carry reproductive risk
CHROMOSOME INVERSIONS
Pericentric: including the centromere, paracentric: excluding the centromere
A segment of the chromosome is reversed in orientation
COPY NUMBER IMBALANCE
Dysmorphism, developmental delay, learning difficulties, specific phenotypes: epilepsy, diabetes, cardiac malformations
CHROMOSOME BREAKAGE SYNDROMES
Fanconi anaemia, ataxia telangiectasia
TYPES OF NON-DISJUNCTION
Meiosis I non-disjunction: triatomic conceptus, monosomic conceptus or uniparental conceptus
Mosaicism: can arise in an initially normal conceptus, due to either non-disjunction or anaphase lag
FISH: FLUORESCENCE IN SITU HYBRIDISATION
You create a DNA probe which is complementary to the target sequence and label it with fluorescent marker
You denature the DNA and then wait for the marker to attach to the sequence if present
You can then see the fluorescent sequence if it has managed to attach
Used in cases when you need quick results for a test, because traditional G-banded chromosomes take about two weeks for results
ARRAY CGH
Many DNA probes are attached to a glass slide
DNA probes bind to complementary DNA sequences
Red spot = more material than control = duplication in genome
Green spot = less material than control = deletion in genome
So it can detect whole chromosome aneuploidy, microdeletion/duplication syndromes, subtelomere imbalances and other regions of imbalance
MLPA
Variation of the multiplex polymerase chain reaction that permits amplification of multiple targets with only one primer.