Chromosome Mutations PDF

CHROMOSOME MUTATIONS: Variation in Number & Arrangement  Chromosome Mutation Chromosome Aberration – disruptions in the normal chromosomal content of a cell – a major cause of genetic conditions in humans, e.g. down syndrome – Includes: change in the total num...

CHROMOSOME MUTATIONS: Variation in Number & Arrangement  Chromosome Mutation Chromosome Aberration – disruptions in the normal chromosomal content of a cell – a major cause of genetic conditions in humans, e.g. down syndrome – Includes: change in the total number of chromosomes Deletion or duplication of genes or segments of a chromosomes Rearrangements of the genetic material either within or among chromosomes. Variation in Chromosome Number 1. Aneuploidy – An organism gains or losses one or more chromosomes, but not a complete set. – 2n + or – minus chromosomes Where n = the number of chromosomes – Types: 1. Monosomy = 2n – 1 2. Trisomy = 2n + 1 3. Tetrasomy = 2n + 2 4. Pentasomy = 2n + 3 2. Polyploidy More than two multiples of the haploid chromosome set are found. Types: – Triploid – 3n chromosomes – Tetraploid – 4n chromosomes – Pentaploid – 5n chromosomes The naming is based on the number of sets of chromosomes found. Aneuploidy Conditions  Non-disjunction The failure of the homologous chromosomes to separate during anaphase Produce certain eggs with two X chromosomes or none (22-XX or 22-0) instead of one (22-X)  Sex Chromosomes Aberrations: 1. Klinefelter Syndrome – "XXY Males", or "47, XXY Males“ – the most common sex chromosome disorder – second most common condition caused by the presence of extra chromosomes – occurs 2 out of every 1,000 males – sterile, have longer arms and legs and taller than their peers – microorchidism (i.e. small testicles) – hypogonadism – decrease testicular hormone – Gynecomastia – breast enlargement – Rounded hips – IQ is below normal range, higher incidence of speech delay and dyslexia (learning disability) 2. Turner Syndrome 45, X0 condition Occurs 1 in 2000 female births 3. Jacob Syndrome 47,XYY condition Above average height – over 6ft tall Subnormal intelligence Controversial – Criminal Syndrome Many males do not exhibit any form of antisocial behavior and lead normal lives There is high incident, but not constant correlation between the extra Y chromosome and the predisposition of males to behavioral problems. 4. Metafemale syndrome 47, XXX condition Occurs in 1 of 1200 female births Underdeveloped secondary sex characteristics Menstrual irregularities and early onset of menopause There’s a tendency towards learning disabilities  Autosome Aberrations 1. Cri-du-chat Syndrome – “chromosome 5p deletion syndrome”, ”5p minus syndrome” or ”Lejeune’s syndrome” – 46,5p- condition – a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children – genetic disorder due to a missing part of chromosome 5 (segmental deletion) – Occurs in between 1 in 20,000 to 1 in 50,000 births – In 80 percent of the cases, the chromosome carrying the deletion comes from the father's sperm rather than the mother's egg  Signs and symptoms usually small at birth, and may have respiratory problems Often the larynx doesn't develop correctly, which causes the signature cat-like cry small head (microcephaly), an unusually round face, a small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose have heart defects, muscular or skeletal problems, hearing or sight problems, or poor muscle tone. Facial features of a patient with Cri du Chat syndrome at: (A)age of 8 months (B)2 years (C)4 years (D) 9 years 2. Down syndrome Trisomy 21 47,21+ Langdon Down discovered it in 1866 1 in every 800 births POLYPLOIDY  Origin 1. The addition of one or more extra sets of chromosomes, identical to the normal haploid complement of the same species (Autopoluploidy) 2. The combination of chromosome sets from different species occurring as a consequence of hybridization (Allopolyploidy)  Autopolyploidy Additional set of chromosome is identical to the parent species Causes: – Failure of all chromosomes to segregate during meiotic division Autotriploids – 3n chromosomes Autotetraploids – 4n chromosomes  Value of Autopolyploid Commercial Value – Plants – horticultural value Increased size of fruits and flowers – Autopolyploids are larger than their diploid relatives – larger in cell size not in greater cell number Experiment – Tetraploids can be produced from diploids – How? Applying cold or heat shock to meiotic cells or by applying colchicine to somatic cells undergoing mitosis.  Colchicine – An alkyloid that interfere spindle formation, and thus replicated choromosome cannot separate at anaphase and do not migrate at opposiste pole. When colchicine is removed, the cell reenter interphase When the paired sister chromatids separate and uncoil, the nucleus contains twice the diploid number of chromosomes and becomes 4n. Economically Important Triploid Plants Potato Bananas Seedless watermelons Apples Stawberry  Allopolyploidy Hybridization of two closely related species A hybrid species resulting chromosome sets as AB maybe sterile due to its inability to produce viable gametes – This happens when chromosomes are not homologous and therefore cannot synapse during meiosis. Allotetraploid or Amphidiploid – Diploid for two genomes derived from different species – AABB chromosome set  Amphidiploid Potential to form balanced gametes thus they becomes reproductively successful Amphidiploid plants: – Cabbage and raddish Unsuccesful – the roots his more like the cabbage and the shoots is more like the raddish. – Wheat and rye (grass family) Wheat – high-yielding grain Rye – growth tolerance in unfavorable environment Combination of high protein content of wheat and high content of the amino acid lysine in rye.  Variation in Chromosome Structure and Arrangement  DELETION The chromosomes breaks in one or more places and a portion is lost Types: – Terminal deletion Near the end of chromosome – Intercalary deletion Interior of the chromosome  DUPLICATION Any part of the genetic material – a single locus or a large piece of chromosome – is present more than once in the genome.  Significance of Duplication 1. Gene Redundancy – Ribosomomal RNA genes Support protein synthesis Support development following fertilization 2. Phenotypic variation – Exhibited in Bar-eyed fruitflies 3. Important source of genetic variability during evolution  INVERSION A segment of a chromosome is turned around 180o within a chromosome It does not involve a loss of genetic information, but simply rearranges the linear gene sequence usually do not cause any abnormalities in carriers as long as the rearrangement is balanced with no extra or missing genetic information individuals which are heterozygous for an inversion, there is an increased production of abnormal chromatids – lowered fertility due to production of unbalanced gametes most common inversion seen in humans is on chromosome 9, at inv(9)(p11q12) – increased risk for miscarriage for about 30% of affected couples  The movement of chromosomal TRANSLOCATION segment to a new location in the genome. balanced translocation, pieces of chromosomes are rearranged but no genetic material is gained or lost in the cell.  unbalanced translocation occurs when a child inherits a chromosome with extra or missing genetic material from a parent with a balanced translocation  Chromosomal Fragile Sites a specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break when the cell is exposed to partial replication stress. more than 120 fragile sites have been identified in the human genome. Types as to frequencies in human population: – Common – Rare  Common Fragile Sites part of normal chromosome structure and are present in all (or nearly all) individuals in a population. At normal conditions, most common fragile sites are not especially prone to spontaneous breaks. are of interest in cancer studies because they are frequently affected in cancer and they can be found in healthy individuals.  Rare Fragile Sites found in less than 5% of the population, and are often composed of two- or three- nucleotide repeats. often susceptible to spontaneous breakage during replication, frequently affecting neighboring genes.  FRAXA Fragile X Syndrome or Martin-Bell Syndrome most common cause of hereditary mental retardation Occurs in 1 in 1250 males; 1 in 2500 females A dominant trait – Males frequently expressed the syndrome than the female; 80% and 30% of the fragile X site is retarded respectively. Phenotypes: mentally retarded, (males) long, narrow faces with protruding chins, enlarged ears, and increased testicular size. FMR-1 Gene responsible for the FRAXA syndrome Trinucleotide repeat – A phenomenon that repeats cluster of three nucleotides (e.g. CGG, CCG, AT-rich repeats) expanding the size of gene, resulting in a disease phenotype. Number of repeats correlates directly in the expression of fragile X syndrome: – 6 to 54 repeats – Normal – 55-200 repeats – “carriers’” of disorder – >200 repeats – expresses the syndrome  6-54 repeats – Transmit gene containing the same number to his or her offspring 55-200 repeats – Transmit to their offspring a gene with an increased number of repeats – Genetic anticipation A phenomenon showing a continuous increase in the number of repeats in the future generation until threshold is reached (200 repeats) Leads to expression of illness or disease  Fragile Site and Cancer FHIT – fragile histidine triad – Located in within a fragile site on chromosome 3 – Altered in cells taken from tumors in individuals with lung cancer The DNA become broken and incorrectly re-fused, resulting in deletions within the gene, thus it is inactivated. A variety of mutation where observed in the cells – Is also a part of another fragile region, FRA3B, which is linked to other cancers,e.g. esophagus, colon and stomach FHIT Highly susceptible to induced breaks in DNA Sensitive to carcinogen-induced damage, creating a susceptibility to cancer