Chromosome Abnormalities
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1 Chromosome Abnormalities Chromosomal abnormalities vs. molecular mutations Simply a matter of size Chromosomal abnormalities are big errors Two types of abnormalities 1. Constitutional problem present in all cells in the body Happens early in development Inheritable 2. Somatic (acquired/spontaneous) problem only in certain cells, others are normal Mosaic Not inheritable Cytogenetics Cytogenetics is the study of chromosomes and chromosomal abnormalities Combination of molecular diagnostics and cell biology Cytogeneticistsobserve cells and chromosomes under the microscope 1. Stop cells in metaphase 2. Stain cells with a suitable dye 3. Observe individual chromosomes 4. Take pictures and organize into a karyotype 1
2 Karyotype Map In a karyotype map, pairs are matched according to their staining characteristics and are numbered sequentially Certain staining results in banding patterns, where segments of chromosomes appear darker or lighter Chromosomes can be identified by their unique banding patterns Genes on the chromosomes with known positions are then numbered Example 3q13.3 designates the location of the thyrotropinreleasing hormone gene 2
3 Try Karyotyping Go to /karyotyping/karyotyping2.html Practice matching chromosomes based on their size and banding patterns FISH 3
4 Incorrect number of chromosomes Euploidy: normal, complete set of chromosomes Polyploidy: 3+ copies of each chromosome Triploid: 3 copies of each chromosome Tetraploid: 4 copies of each chromosome Polyploidy can be result of 2 sperm fertilizing one egg or failure of zygote to make first division not compatible with life in humans Polyploidy common in other organisms, such as plants Incorrect number of chromosomes Aneuploidy: loss or gain of a particular chromosome Trisomy: 3 copies of any particular chromosome Trisomy 21 leads to Down Syndrome Monosomy: missing a copy of a particular chromosome Monosomy X in Turner syndrome The most common cause of aneuploidy is nondisjunction, which is the failure of chromosomes to disjoin normally during meiosis The resulting gamete either lacks a chromosome or has two copies 4
5 Aneuploidy: Klinefelter s Syndrome (extra X chromosome) Aneuploidy: Turner s Syndrome (only one X) 5
6 Structural chromosome abnormalities Chromosomes can be damaged and break during either mitosis or meiosis Broken chromosomes are typically repaired, but sometimes damage is not repaired or improperly repaired Translocation: interchange of genetic material between nonhomologous chromosomes Translocations Reciprocal translocations: breaks occur in two different chromosomes and material is mutually exchanged Carriers typically unaffected, but offspring may have partial trisomy or partial monosomy Translocations Robertsonian Translocations: short arms of two nonhomologous chromosomes are lost and the long arms fuse together at the centromere, making a single chromosome 6
7 Other abnormalities Deletions Duplications Inversions Isochromosomes Ring chromosomes Cri-du-chat Syndrome Consequences of breakages Remember each chromatid is a double helix molecule of DNA The unique chromosomal location of a particular gene or DNA sequence is the locus Breakages can affect genes the break may occur within a gene, altering its function translocated genes may come under the influence of different promoters and enhancers so that their expression is altered the breakpoint may occur within a genecreating a hybrid gene, which results in a protein with an N-terminal of one normal cell protein coupled to the C-terminal of another 7
8 CLINICAL SIGNIFICANCE OF A MUTATION Depends on: type of mutation its location within the gene tissue involved, since not all tissues express all genes Is it inheritable or not? 8
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