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

  1. You create a DNA probe which is complementary to the target sequence and label it with fluorescent marker

  2. You denature the DNA and then wait for the marker to attach to the sequence if present

  3. 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

  1. Many DNA probes are attached to a glass slide

  2. DNA probes bind to complementary DNA sequences

  3. Red spot = more material than control = duplication in genome

  4. 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.

#genomics

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