Chapter 2: Chromosome Abnormalities Introduction First get the basics clear.

There are 23 pairs (that means 46 in TOTAL) of chromosomes in a human nucleus. 1 to 22 are autosomal. 23 is the sex chromosome, X and Y. This chapter will explore what can go wrong in replication. It can be numerical or structural. Numerical means that there could be an extra or deficiency of a whole chromosome. Structural abnormalities refer to specific sections within a chromosome, which is somehow differently arranged. So that means you might have extra genes or some may have switched position or it may have connected to another part. All these have specific terms attached to them, which will be mentioned later on. Numerical Trisomy abnormalities are the most significant and are found on chromosomes 21, 18 and 13. Abnormalities associated with the other chromosomes are not compatible with life. Trisomy 21 This is the most common autosomal abnormality. It is the cause of down syndrome (which can also becaused by structural abnormality). What happens is during M1 phase of meiosis, the homologous sister chromatids fail to separate giving a total number of 48 chromosomes instead of the usual 46. This is called the M1 non-dysjunction. Non-dysjunctions refers to a failure in separation. Another possibility is the same things happening in the M2 phase of meiosis. This is called M2 non-dysjunction. This process is particularly relevant to the age of women getting pregnant. As the older a woman get, the more likely it is for the baby to develop these abnormalities. In men, the cycle of meiosis lasts for 3 days. For women it starts at puberty and pauses at M1, and only completes meiosis when it is fetilised. How does trisomy cause down syndrome? Well, chromosome 21 codes for transacting factors. So having an extra one causes these genes to be expressed even more. Transacting factors regulate transcription. So basically you have more of them and it really messes up things causing genomic chaos. XXY Syndrome (Klinefelter's Syndrome) This occurs when males have an extra x-chromosome. This causes hypogonadism, which is when the sex glands produce little or no hormones. It affects sexual development of the individual. Visually observable things will be like gynaecomastia which is the enlargement of the breast from increased oestrogen. X0 Syndrome (Turner's Syndrome) This occurs when there is a missing x-chromosome. Most are incompatible with life but those who survive generally do quite well.

Structural Translocations are the most common type of chromosomal structural abnormality. It can happen two ways. One possibility is when exchange of genetic material between NON-HOMOLOGOUS chromosomes. The other possibility is if NON-HOMOLOGOUS chromosomes end us joining together. Robertsonian Translocation This is where two acrocentric (very short p arm) chromosomes fuse to form one submetacentric (two arms different lengths) chromosome. Balanced: there will be one pair of normal chromosomes. Unbalanced: both pairs will be abnormal. RT is one of the causes of down syndrome. Common chromosomes involved is 14 and 21, where they fuse together and form abnormal chromosomes. This type of down syndrome happens more often in families. Another mechanism of down syndrome is a duplication on chromosome 21, with the specific band q22.2 which is the down syndrome critical region. Reciprocal Balanced Translocation This is when segments are exchanged between two NON-HOMOLOGOUS chromosomes. What you end up with is FOUR chromosomes and no homologues. This type of translocation is normally associated with learning difficulties. It is hard to find out what is wrong, you can only deduce from testing various family members and compare. During DNA recombination, there may be deletions which may cause the strand to break. Now if it breaks there is not usual telomere at the end of the strand stopping it from combining with another strand. So this is how two ends could join together. Non-allelic Homologous Recombinations This happens during recombination and micro deletions occur. Strong corelation with specific clinical diseases, linked with specific deletions in chromosomes. They have very distinct facial features. Imaging Use FISH and aCGH.