Chromosome Abnormalities

PolyploidyLoss or gain of whole chromosome set1-3% pregnancies Can happen when two sperm fertilise one egg - or diploid zygoteSeldom survive to termAneuploidyLoss or gain of chromosomesOnly trisomy 13 (Patau) ,18 (Edward's) and 21 (Down's) can survive to terme.g. Down's Syndrome - 47, XX, +21 or 47, XY, +21Turner Syndrome - 45, XOKlinefelters - 47, XXY Caused by nondisjuntion -Failure of homologous chromosomes to separate in Anaphase I-Or failure of sister chromatids to separate in Anaphase II or anaphase lag -Failure of chromosome/chromatid to be incorporated into a nucleus as a result of delayed movement during anaphase. These chromosomes are lost resulting in a daughter cell that is deficient.

TranslocationRobertsonianTranslocation between acrocentric chromosomes (13,14,15,21,22) - commonly 13 and 14Individual has 45 chromosomes as 2 have fusedCarriers clinically normalCan have implications for Offspring - e.g. greater risk of Down's Syndrome 21:21 fusion will never give normal offspring - either trisomy 21 (Down's) or monosomy 21 (lethal) Reciprocal When breaks occur in two different chromosomes and material is mutually exchanged The resulting chromosomes are called derivative chromosomes Carriers are unaffected because they still have the complete complement of genetic material (a reciprocal balanced translocation) Carrier’s offspring can be normal, carry the translocation or can have deletions or duplications of genetic material (unbalanced translocation) This will be either partial trisomy or partial monosomy resulting in an abnormal phenotype How does this happen? Either 2:2 segregation can occur which can be alternate or adjacent or 3:1 segregation can occur at meiosis. See right 2:2 Segregation Alternate – A and D will go into one gamete and C and B into another. This is balanced. Adjacent – A and C will go into one gamete and B and D into another. This is unbalanced. 3:1 Segregation If A C and D segregate together this is unbalanced. Resulting in trisomy for material on C in one gamete and monosomy for material on B in another gameteInversion 2 breaks occur in the chromosomeThe reinsertion of the fragment is then in inverted orderThey are a balanced structural rearrangement so don’t alter phenotype in the carrier Pericentric – involve the centromere Paracentric – don’t involve the centromere (only on one arm) Inversions can interfere with meiosis, producing abnormalities in offspring due to deletions or duplications if crossing over occurs within the inversion If it is a pericentric inversion this can result in an acentric (no centromere) or dicentric (two centromeres) chromatidRing When deletions occur at both tips of the chromosome Ends then fuse, forming a ring If they contain a centromere, it can proceed through cell division However they are often lost resulting in monosomy for the chromosomeWhen found in humans they are normally mosaic with rings in some cells and monosomy in otherse.g. ring chromosome 20 syndrome - epilepsyInsertionsSegment of one chromosome inserted into the other Can result in a frame shift Also can disrupt gene exons If the chromosome with the insertion is coupled with the chromosome with the deletion in the gamete then this is balanced. If not gametes will be abnormal (50%) Deletion Very rare Can be ‘de novo’ mutation or inherited as a result of translocation or inversion in the parent Interstitial – loss of middle segment of chromosome e.g. Prader-Willi syndrome – a small deletion of seven genes Terminal – loss of end of chromosome Results in partial monosomySerious clinical effect e.g. cri-du-chat syndrome (5p15): child has distinctive cry. Caused by a deletion of the distal short arm of chromosome 5. Results in mental retardation, small head, many survive to adulthood

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Numerical

Structural