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Ploidy presentation


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Ploidy, Types: Autoploidy, Aneuploidy, Turner syndrome, Patau syndrome, Cri du chat syndrome, Ploidy experiment in plants, Robertsonian translocation, Down syndrome, Trisomy, Nullisomy, Monosomy, Genetic disorders.

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Ploidy presentation

  1. 1. Understanding Ploidy, Types, and related Genetic disorders Dr. Ishan Y. Pandya PhD, M.Sc., M.B.A. Biotechnology E-mail: Gujarat Ecological Education and Research (GEER) Foundation Gandhinagar, Gujarat, India 1
  2. 2. The Abc of genetics.. • We are diploid organisms with two sets of homologous chromosomes,but we contain haploid sex cells also with one set and half the number. • Genetics is a rife with potentially confusing scientific terminologies associated with chromosomes, chromosome number ,what is ploidy, which cells are haploid, which are diploid, what are homologous chromosomes etc.. 2
  3. 3. Diploid number: • most of the cells in the body are somatic ,or non sex-cells and have a diploid (2n) chromosome number.diploid means that the chromosomes in pair and are called homologues.every somatic cell in your body has 46 chromosomes, half from each parent. 3
  4. 4. Haploid number • Most but not all the cells in the body are cells also called gametes have half the number of chromosomes as do the somatic cells. • These gametes are reffered to as being haploid(n). 4
  5. 5. • A haploid and a diploid cell… 5
  6. 6. Ploidy • Ploidy refers to the number of basic chromosome sets • Say for eg. A diploid has 2 sets where as a hexaploid has 6 sets. • The basic chromosome number x,also called the monoploid number is the number of different chromosomes that make up a single complete set. 6
  7. 7. Ploidy , mitosis and meiosis • Mitosis : equational division takes place in somatic cells • Meiosis: reductional division takes place in vegetative cells 7
  8. 8. Ploidy Euploidy Aneuploidy 8 Ploidy can be Further divided into two groups based on the type of change in the chromosome number.
  9. 9. Euploidy : The condition of an organism having complete set of chromosomes or multiples of the basic set is euploidy and the cell is said to be euploid. Aneuploidy: This is a condition where the chromosome number is not an exact multiple of the normal diploid number, with either fewer or more than the normal number of chromosome in the cell. 9
  10. 10. Ploidy Euploidy Aneuploidy Monoploidy Polyploidy hypoploidy hyperploidy monosomy nullisomy trisomy tetrasomy Only in plants autopolyploidy allopolyploidy 10
  11. 11. Euploidy.. Euploidy Monoploidy (x) Polyploidy (3x,4x,5x..) 11 • The condition of an organism having complete set of chromosomes or multiples of the basic set is euploidy and the cell is said to be euploid.
  12. 12. Euploidy is lethal in most animal species, but often tolerated in plants, where it has played a role in speciation and diversification. Monoploidy and polyploidy involve complete sets of chromosomes, and so both are cases of euploidy. 12
  13. 13. Variations in number of complete chromosome sets. 13
  14. 14. Causes of occurrence of monoploidy and polyploidy. Monoploidy and polyploidy can result when either round of meiotic division lacks cytokinesis, or when meiotic nondisjunction occurs for all chromosomes. a. Complete nondisjunction at meiosis I will produce 1⁄2 gametes with normal chromosomes, 1⁄2 with no chromosomes. 14
  15. 15. b. A gamete with two sets of chromosomes fused with a normal gamete produces a triploid (3N) zygote. c. Fusion of two gametes that each have two sets of chromosomes produces a tetraploid (4N) zygote. d. Polyploidy of somatic cells can result from mitotic nondisjunction of complete chromosome sets 15
  16. 16. Monoploidy.. • An individual that contains one half the normal number of chromosomes is a monoploid and exhibits monoploidy. • Some species such as bees, ants and male bees are normally monoploid because they develop from unfertilized eggs. Consequently, these individuals will be sterile. 16
  17. 17. • Monoploids are very rare in nature because recessive lethal mutations become unmasked, and thus they die before they are detected. • These alleles normally are not a problem in diploids because their effects are masked by dominant alleles in the genome. 17
  18. 18. • A stage in the life cycle of some fungal species can also be monoploid. • Monoploidy has been applied in plant biotechnology to rapidly develop plants from anthers that have a fixed genotype. 18
  19. 19. Plant experiments often use monoploids. i. Haploid cells are isolated from plant anthers and grown into monoploid cultures. ii. Colchicine (which inhibits mitotic spindle formation) allows chromosome number to double, producing completely homozygous diploid breeding lines. iii. Mutant genes are easily identified in monoploid organisms. 19
  20. 20. Production of monoploid plants from diploid. 20
  21. 21. • Polyploidy.. • Polyploidy occurs in cells and organisms when there are more than two homologous sets of chromosomes. • Very common in plants – associated with origin of new species – may positively correlate to size of individual. 21
  22. 22. – There are two classes of polyploids based on the number of chromosome sets: • . Even-number polyploids are more likely to be at least partially fertile, because the potential exists for equal segregation of homologs during meiosis. • . Odd-number polyploids will always have unpaired chromosomes. Balanced gametes are rare and these organisms are usually sterile or have increased zygote death. 22
  23. 23. Triploids, pentaploids (all with odd number of chromosome sets) are often sterile due to pairing problems during meiosis... 23
  24. 24. Even numbers of chromosomes in polyploids may lead to more normal segregation and partitioning of chromosome sets... 24
  25. 25. • Polyploid types are labelled according to the number of chromosome sets in the nucleus: • triploid (three sets; 3x), for example the phylum Tardigrada • tetraploid (four sets; 4x), for example Salmonidae fish • pentaploid (five sets; 5x) 25
  26. 26. • hexaploid (six sets; 6x), for example wheat • oktoploid (eight sets; 8x), for example Acipenser (genus of sturgeon fish) • dekaploid (ten sets; 10x), for example certain strawberries • dodecaploid (twelve sets; 12x), for example the plant Celosia argentea 26
  27. 27. • The occurrence of polyploidy is a mechanism of speciation . • Polyploid animals are often sterile, so they often reproduce by parthenogenesis. • Polyploid salamanders and lizards are also quite common and parthenogenetic. • While mammalian liver cells are polyploid, rare instances of polyploid mammals are known, but most often result in prenatal death. 27
  28. 28. • Plants are generally bigger in strature. • The plants are specially sterile when if they have odd numbered chromosome set. • Polyploidy tolerated in plants because of self-fertilization; plays an important role in plant speciation and diversification. 28
  29. 29. 9 Bio 312 FALL 03 Polyploidy in Animals? (lethal in humans) Some amphibians (sexual cycle) Some salamanders, four-legged reptile (parthenogenetic) Some fish (salmonids have 2X DNA of related fish) Triploid oysters developed - sterile Flatworms (Platelminti) Leeches (sanguisughe) Brine shrimp (Artemia) Reproduce by parthenogenesis (special type of unfertilized egg develops into embryo) 29
  30. 30. Size variations of stomata. 30
  31. 31. Polyploidy Autopolyploidy Allopolyploidy 31 • Polyploidy occurs in two types in plants.
  32. 32. Types of polyploidy in plants.. 32 Additional sets identical to parents Hybridization of closely related species; often sterile
  33. 33. Autopolyploidy.. Autopolyploids results when all sets of chromosomes are from the same species, usually due to meiotic error. 33
  34. 34. Can arise spontaneously through nondisjunction of a whole chromosome set. • Triploids commonly made by crossing diploids to tetraploids. 2n X 4n = 3n progeny (many seedless fruits) • Tetraploids can be induced by treatment with colchicine . 34
  35. 35. • Examples include: – (1) “Seedless” fruits like bananas (3n = 33), grapes and watermelons. – (2) Grasses, garden flowers, crop plants and forest trees 35
  36. 36. Allopolyploidy.. – hybrid of two or more closely related species – partially homologous chromosomes (homeologous) Allopolyploidy is caused by the presence of several genomes of different species in a cell, a tissue or a whole organism. 36
  37. 37. • For example: – (1) Fusion of haploid gametes from species 1 and species 2 produces an N1 + N2 hybrid plant. No chromosomal pairing occurs at meiosis, viable gametes are not produced and the plants are sterile. – (2) Rarely, division error or cold shock doubles the chromosome sets (2 N1 + 2N2). The diploid sets function normally in meiosis, and fertile allotetraploid plants result. – (3) An example is crosses between cabbages (Brassica oleracea) and radishes (Raphanus sativus), which both have a chromosome number of 18. 37
  38. 38. If pairing partners can be provided for homologs in allopolyploids, sterility can be relieved…e.g. Karpechenko (1928) 38 Amphidiploids = nonidentical chromosome sets doubled in allopolyploid Haploid number (n) = 18 Monoploid number (x) = 9 Chromosome sets unpaired Different Species
  39. 39. Polyploidy is the rule in agriculture, where polyploids include all commercial grains (e.g., bread wheat, Triticum aestivum (2n = 42), an allohexaploid of three plant species), most crops and common flowers. 39
  40. 40. Mosaicism. • A mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual, who has developed from a single fertilized egg. • Mosaicism may result from a mutation during development which is propagated to only a subset of the adult cells. 40
  41. 41. • The most common form of mosaicism found through prenatal diagnosis involves trisomies. • Although most forms of trisomy are due to problems in meiosis and affect all cells of the organism, there are cases where the trisomy only occurs in a selection of the cells. • This may be caused by a nondisjunction event in an early mitosis, resulting in a loss of a chromosome from some trisomic cells. 41
  42. 42. • An example of this is one of the milder forms of Klinefelter's syndrome, called 46/47 XY/XXY mosaic wherein some of the patient's cells contain XY chromosomes, and some contain XXY chromosomes. • The 46/47 annotation indicates that the XY cells have the normal number of 46 total chromosomes, and the XXY cells have 47 total chromosomes. 42
  43. 43. A mosaic fruit fly- Bilateral Gyandromorph (both Male and Female Genotypes) 43 Female (XX) half: heterozygous for both markers Male (XO) half: white, miniature wing Occurs from loss of one X (with wildtype alleles) at 1st mitotic division during development, oriented bilaterally.
  44. 44. Robertsonian translocation • A Robertsonian translocation is a type of in which two nonhomologous acrocentric chromosomes (chromosomes that are not members of the same pair and have centromeres near their ends) break at their centromeres. • The long arms may become attached to a single centromere and serve a function. The short arms also join to form a reciprocal product, which typically contains nonessential genes and is usually lost within a few cell divisions. 44
  45. 45. • In humans, when a Robertsonian translocation joins the long arm of chromosome 21 with the long arm of chromosome 14 (or 15), the heterozygous carrier is phenotypically normal because there are two copies of all major chromosome arms and hence two copies of all essential genes. • However, the progeny of this carrier may inherit an unbalanced trisomy 21, causing Down Syndrome. 45
  46. 46. • About one in a thousand newborns has a Robertsonian translocation. • The most frequent forms of Robertsonian translocations are between chromosomes 13 and 14, 13 and 21, and 21 and 22 46
  47. 47. • In several forms, Robertsonian translocations cause chromosomal deletions or addition and result in syndromes of multiple malformations, including trisomy 13 ( Patau syndrome) and trisomy 21 ( Down syndrome). 47
  48. 48. Non Disjunction • Disjunction refers to the normal seperation of homologous chromosomes or chromatids to opposite poles at nuclear division. • Non disjunction refers to the failure of normal seperation of homologous chromosomes or chromatids to opposite poles at nuclear division. 48
  49. 49. • There are two possibilities mainly for the disjunction to fail: Meiosis I Meiosis II Non Disjunction at Meiosis I is more common than Meiosis II. 49
  50. 50. Causes: • Microtubule inhibitors cause non-disjunction. • Formation of tetrad is critical for correct disjunction since disomic gametes are usually non-recombinant. • Mutations that interfere with recombination increase the frequency of meiosis I non- disjunction. 50
  51. 51. 51
  52. 52. Non disjunction of X chromosome 52 Nondisjunction also occurs with autosomes
  53. 53. Aneuploidy.. This is a condition where the chromosome number is not an exact multiple of the normal diploid number, with either fewer or more than the normal number of chromosome in the cell. 53
  54. 54. Causes: • A condition of aneuploidy may occur due to loss of one or more chromosomes during mitosis or meiosis • Due to non disjunction i.e irregular distribution of sister chromatids. 54
  55. 55. Origin of aneuploids 55
  56. 56. • In diploid organisms aneuploid variations take four main forms that can be classified under two main groups: • Hypoploidy: loss of one or more chromosomes from basic set. • Hyperploidy: presence of one or more chromosomes in the basic set. 56
  57. 57. Aneuploidy Hypoploidy Hyperploidy Monosomy 2n-1 Nullisomy 2n-2 Trisomy 2n+1 Tetrasomy 2n+2 57
  58. 58. Normal (theoretical) set of metaphase chromosomes in a diploid (2N) organism (top) and examples of aneuploidy (bottom) 58
  59. 59. Monosomy.. • It’s a form of aneuploidy with the presence of only one chromosome (instead of a pair in humans)from a pair. • A monosomic cell hence involves a loss of a single chromosome that is the cell is 2n-1. • Partial monosomy occurs when only a portion of the chromosome has one copy while the rest has 2 copies. 59
  60. 60. Causes: • This condition mainly occurs due to the non disjunction in meiosis in parent producing a gamete with no copies of a particular chromosome and one copy of all other chromosomes in the set. • The number of possible monosomics in an organism is equal to its chromosome number. 60
  61. 61. • Monosomy is usually not tolerated in diploids but can be easily introduced in polyploids,however several experiments have been carried out and certain degree of success has been observed. • Usually autosomal lethal due to dosage imbalance. 61
  62. 62. Human monosomies • Turner Syndrome • Cri du chat syndrome 62
  63. 63. Turner Syndrome • Turner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which monosomy X is the most common. • It occurs in about 1 out of every 2500 female births.Instead of the normal XX sex chromosomes for a female, (or XY for a normal male) only one X chromosome is present and fully functional. 63
  64. 64. • In rarer cases a second X chromosome is present but abnormal, while others with the condition have some cells with a second X and other cells without it (mosaicism). • A normal female karyotype is labeled 46,XX; individuals with Turner syndrome are 45,X. In Turner syndrome, female sexual characteristics are present but generally underdeveloped 64
  65. 65. History… • The syndrome is named after Henry Turner, an Oklahoma endocrinologist, who described it in 1938. • In Europe, it is often called Ullrich-Turner syndrome or even Bonnevie-Ullrich-Turner syndrome to acknowledge that earlier cases had also been described by European doctors. 65
  66. 66. Symptoms • Short stature • Lymphedema (swelling) of the hands and feet • Broad chest (shield chest) and widely-spaced nipples • Low hairline • Low-set ears • Reproductive sterility 66
  67. 67. Incidence Approximately 98% of all fetuses with Turner syndrome result in miscarriage. • Turner syndrome accounts for about 10% of the total number of spontaneous abortions in the United States. • The incidence of Turner syndrome in live female births is believed to be 1 in 2500 67
  68. 68. Diagnosis • Turner syndrome may be diagnosed by amniocentesis during pregnancy. • Sometimes, fetuses with Turner syndrome are identified by abnormal ultrasound findings (i.e. heart defect, kidney abnormality). • Although the recurrence risk is not increased, genetic counseling is often recommended for families who have had a pregnancy or child with Turner syndrome. • A blood test, called a karyotype, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome. 68
  69. 69. Cri du chat syndrome • Cri du Chat syndrome or Cri-du-Chat syndrome (French for Cry or call of the cat referring to the specific cry of the child), also called deletion 5p syndrome, 5p minus or Lejeune’s syndrome, is a rare genetic disorder due to a missing portion of chromosome 5. • 69
  70. 70. • It was first described by Jérôme Lejeune in 1963. • The condition affects an estimated 1 in 20,000 to 50,000 live births. • The disorder is found in people of all ethnic backgrounds and is more common in females by a 3-1 ratio 70
  71. 71. Symptoms • The syndrome gets its name from the characteristic cry of infants born with the disorder. • The infant sounds just like a meowing kitten, due to problems with the larynx and nervous system. • This cry identifies the syndrome 71
  72. 72. Diagnosis • Diagnosis is based on the distinctive cry and accompanying physical problems. • Genetic counseling and genetic testing may be offered to families with individuals who have cri du chat syndrome. 72
  73. 73. 73 Mental retardation, abnormal development of glottis and larynx 1 / 50,000 live births Partial Monosomy: Cri-du-chat Syndrome (46, -5p)
  74. 74. A case of double monosomy • Double monosomy mosaicism was reprted in a retarded child with multiple congenital malformations. • Double monosomy mosaicism was observed in a three-year-old girl who had mental and physical retardation. 74
  75. 75. Routine blood-lymphocyte and bone-marrow chromosome studies showed an apparent 45, X pattern, which was confirmed by autoradiographic studies with tritiated thymidine. 75
  76. 76. • Routine and fluorescent chromosome analyses from bilateral skin biopsies revealed a 45,XX,21- karyotype, which was consistent. • Although her clinical features bore some resemblance to patients with Turner's syndrome, the patient did not closely fit either of these syndromes 76
  77. 77. Nullisomy.. • Involves loss of one homologous chromosome pair that is the cell is 2N-2. • Its lethal in diploids. • Can be tolerated in bread wheat - it’s a hexaploid - behaves meiotically like a diploid - 4 homologous chromosomes compensate for missing pair of homologs Sears isolated 21 nullisomics in wheat 77
  78. 78. Cause: • Mainly due to non disjunction occuring for the same chromosome in meiosis in both parents producing gamete each with no copies that chromosome and one copy of all other chromosomes in the set. 78
  79. 79. Neuronal migration defect in BRCA1 gene • A BRCA1 5382insC mutation was identified in a family with multiple cases of breast and ovarian cancer and eastern European ancestry. • Predictive genetic testing was offered to all family members after standard genetic counselling within the regional clinical genetics service. a case of a possible nullisomy. 79
  80. 80. From the diaries… • chromosomal abnormalities in sperm from patients with oligoasthenoteratozoospermia(OAT) resulted in the detection of double aneuploidy (double monosomic and double nullisomic conditions)using in situ hybridization using one probe set. 80
  81. 81. Trisomy.. • A chromosomal anomaly that is characterized by presence of an extra chromosome in the cells of a person or a plant body. • A trisomic cell involves an extra chromosome that is, the cell has three copies of one chromosome type and two copies of every other chromosome type. • A trisomic cell is 2N+1. 81
  82. 82. • A partial trisomy occurs when part of an extra chromosome as opposed to a whole extra chromosome occurs. • Trisomies are viable. several can live to adulthood ,are fertile and can produce viable meiotic products. 82
  83. 83. Examples of most common trisomic conditions. • Trisomy 21 : Down Syndrome • Trisomy 18 : Edward’s Syndrome • Trisomy 13 : Patau’s Syndrome 83
  84. 84. Down Syndrome • In trisomy 21, the presence of an extra set of genes leads to over expression of the involved genes, leading to increased production of certain products. • For most genes, their over expression has little effect due to the body's regulating mechanisms of genes and their products. But the genes that cause Down syndrome appear to be exceptions. 84
  85. 85. A few genes in ….. • COL6A1 -- overexpression may be the cause of heart defects • ETS2 -- overexpression may be the cause of skeletal abnormalities • CAF1A -- overexpression may be detrimental to DNA synthesis • Cystathione Beta Synthase (CBS) -- overexpression may disrupt metabolism and DNA repair • DYRK -- overexpression may be the cause of mental retardation • CRYA1 -- overexpression may be the cause of cataracts 85
  86. 86. Features .. • One of the more notable aspects of Down syndrome is the wide variety of features and characteristics of people with trisomy 21. • There is a wide range of mental retardation and developmental delay noted among children with Down syndrome. Some babies are born with heart defects and others aren't. 86
  87. 87. Why is it so • 1. alleles • 2.penetrance 87
  88. 88. • Because of the small size of the 21st chromosome and its association with Down syndrome, it is a heavily mapped human chromosome. • Research is focusing on trying to identify genes and their effects when overexpressed. 88
  89. 89. Trisomy: Down Syndrome (47, +21) 89 Characteristic facial patterning, mental retardation
  90. 90. Edward’s Syndrome • Trisomy 18 is the second most common trisomy and occurs when a baby has three of the eighteenth chromosome. • This results in 47 chromosomes instead of the normal 46 in the affected cells. It is this extra genetic material that causes the problems associated with Trisomy 18. 90
  91. 91. • Trisomy 18 is also called Edwards syndrome (or Edward's syndrome) and occurs in about 1:3000 live births. • Unlike Down syndrome, Trisomy 18 is usually fatal, with most of the babies dying before birth and those who do make it to birth typically living only a few days. • However, a small number of babies (<10%) live at least one year. 91
  92. 92. Features… Some of the typical characteristics of Trisomy 18 can include heart defects such as • VSD (Ventricular Septal Defect )- a hole between the lower chambers of the heart • ASD (Atrial Septal Defect) - a hole between the upper chambers of the heart • coarctation of the aorta (a narrowing of the exit vessel from the heart) • kidney abnormalities • omphalocele (a portion of the intestinal tract is located outside the stomach in a sac) 92
  93. 93. Patau Syndrome • The syndrome or trisomy 13 is the least common trisomic condition observed.It is a full trisomic condition. • In this disorder three copies of chromosome 13 are present thereby bringing about a diseased condition. • The occurrence of the disorder is 1 in 5000 live births. 93
  94. 94. The symptoms include • facial defect • Polydactyly • Characteristic facial features • Retarded growth • Poorly developed sexual characters 94
  95. 95. Tetrasomy • The condition of a tetrasomic cell involves an extra chromosome pair resulting in the presence of four copies of one chromosome and two copies of every other chromosome type. • A tetrasomic cell is hence 2N+2. 95
  96. 96. Causes • This could arise if non disjunction occurs for the same chromosome in meiosis in both parents producing gamete each with two copies of that chromosome and one copy of all other chromosomes in the set. 96
  97. 97. • We have a condition of a double tetrasomy with a cell with 2N+2+2 that has two chromosomes present in four copies each. • A disorder associated with tetrasomic condition in humans is the klinefelter’s syndrome. 97
  98. 98. Klinefelter’s syndrome • Klinefelter's syndrome, 47,XXY or XXY syndrome is a condition caused by a chromosome aneuploidy. Affected individuals have at least two X chromosomes and at least one Y chromosome. 98
  99. 99. • The principal effects are development of small testicles and reduced fertility. • A variety of other physical and behavioral differences and problems are common, though severity varies and many boys and men with the condition have few detectable symptoms. • Affected males are almost always effectively sterile, although advanced reproductive assistance is sometimes possible. • Some degree of language learning impairment may be present,and neuropsychological testing often reveals deficits in executive functions. 99
  100. 100. • In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). • The second most common extra chromosome condition, it is named after Dr. Harry Klinefelter, an endocrinologist at Massachusetts General Hospital, Boston, Massachusetts, who first described it in 1942. • The condition exists in roughly 1 out of every 500 males. 100
  101. 101. examples • Double autosomal tetraploidy is very rare in live births as well as abortuses. • But a case of an abortus with 48 chromosomes with 2 extra chromosomes was reported with double trisomy or tetrasomy. • The studies reveal that the anomaly might have occurred during the parental gametogenesis. 101
  102. 102. • This may have arisen due to non disjunction at both the meiotic stages or a double non disjunction during the first meiotic division possibly during oogenesis if we assume that the spermatozoa with a disomy or trisomy is inviable. • This was a rare observation marking by professor Dhadial from the paediatric research unit Guy’s hospital and medical school london. 102
  103. 103. conclusion • From the knowledge gained by far we can analyze the cituation and predict the role of ploidy in the evolutionary processes that have been undergoing and the ones that are. • One of the major roles played by the ploidy can be clearly visualised in the evolution,plant speciation,generation and production of better varities of plants,crops,seeds and other products. 103
  104. 104. And the journey continues….. • We can efficiently study and monitor the species interrelationships and evolutionary characteristics in major areas. • It is now possible to get a clear idea of the genetic make up of an organism. • With this one can correlate the changes observed with the evolutionary evidences to correlate evolutionary conservativeness, breakpoints and trace the path of evolution. • And the story continues……. 104
  105. 105. Bibliography • I genetics – Peter russel • The american naturalist- vol 74 G.Ledyard • Botany online – classical genetics • The journal of medical genetics online • Trisomy 18 foundation 105
  106. 106. • Lecture series- university of california • Wikipedia • Molecular genetics disease mechanism- R.Daniel Gietz • Nature periodicals • Ploidy – Tami port • …… 106
  107. 107. • KARGER-cytogenetic and genomic research. • Journal of medical genetics • PUBMED • • The story of the down syndrome – len leshin • Rainbows down under foundation 107
  108. 108. Human intelligence is divergent evolution……….. 108