The document discusses cytogenetics, which involves the study of chromosomes through cell culture and karyotyping. Chromosomes can be analyzed for their number and structure to detect abnormalities. Specific staining techniques like Q-, G-, R-, and C-banding produce distinct banding patterns that allow identification of each chromosome type. Karyotyping involves organizing chromosomes based on these patterns to detect any abnormalities associated with diseases.

2. The study of chromosome and the related disease states caused by abnormal chromosome number and\or structure. Chromosomes : complex structures located in the cell nucleus, composed of DNA, histone and non-histone proteins, RNA, and polysacchairdes. Cytogenetics involves the study of chromosomes. Both the number and structure of the chromosomes are analyzed.

3. A tissue that can be stimulated to undergo cell division in-vitro It is only during mitosis of the cell cycle that distinct chromosomes can be visualized with a light microscope Examples of tissues that can be studied: chorionic villi, amniotic fluid, peripheral blood (lymphocytes), skin (fibroblasts), bone marrow

4. Cells are stimulated to divide and are incubated for 48-96 hrs. Cells are arrested at mitosis Cells are “dropped” onto glass slides and G-banded

6. Each chromatid represents one molecule of DNA

7. Effect Area Stained Stain Type Under UV light, distinct fluorescent banded pattern for each chromosome. Chromosome arms; mostly repetitive AT-rich DNA Quinacrine Q-banding Distinct banded pattern for each chromosome; same as Q-banding pattern except single additional band near centromere of chromosomes 1 and 16 Chromosome arms; mostly repetitive AT-rich DNA Giemsa G-banding Reverse banding pattern of that observed with Q- or G-banding Chromosome arms; mostly unique GC-rich DNA Variety of techniques R-banding Largest bands usually on chromosomes 1, 9, 16, and Y; chromosomes 7, 10, and 15 have medium-sized bands; size of C-bands highly variable from person to person Centromere region of each chromosome and distal portion of Y chromosome; highly repetitive, mostly AT-rich DNA Variety of techniques C-banding

8. Non-Banded Karyotype

10. Chromosomes can be identified by: Their size Their shape (the position of the centromere) NB Chromosomes are flexible Banding patterns produced by specific stains (Giemsa) Chromosomes are analysed by organising them into a KARYOTYPE © Biologyreference.com

12. Short arm of the chromosome = p Long arm of the chromosome = q Bands are numbered independently on the short and long arms

14. 7 18 Low/High Resolutions Karyotype

16. Normal Karyotype/ Ideogram

17. Q-Banding

18. C-Banding

19. R - Banding

20. Advantages 1- Enable the entire genome to be viewed at one time. 2- Suitable when a specific anomaly is suspected ( e.g. Philadelphia in CML ) and as a general diagnostic tool to detect additional chr. Abnormalities commonly seen in disease progression of CML. Disadvantages 1- Detect major structural abnormalities ( one band = 6mb of DNA ~ 150 genes ). 2- Labor intensive and highly dependent upon operator experience and skills. Advantages and Disadvantages of conventional technique

21. 46,XY 46,XX 47,XX,+21 45,XO 46,XY,5p- 46,XX,t(9;22) 46,XY,del(15q11-q13)

22. Chromosomes can be identified by: Their size Their shape (the position of the centromere) NB Chromosomes are flexible Banding patterns produced by specific stains (Giemsa) Chromosomes are analysed by organising them into a KARYOTYPE © Biologyreference.com

23. A) Polypoidy – change in complete sets of chromosomes (3n, 4n, etc) plants > animals. Autopolyploidy vs Allopolyploidy Plants  more yeild Animals  parthenogenesis B) Aneuploidy – change in the no. of chromosomes nullisomy 2n-2 monosomy 2n-1 trisomy 2n+1 tetrasomy 2n+2 Gene dosage effect 1 - Sex-chromosomal aneuploids . 2 - Autosomal aneuploids .

26. Chromosome rearrangements: Effects Deletion. pseudodominance Duplication. gene dosage Inversion – paracentric positional pericentric Translocation. positional new linkage rearrangement

27. Extra single chromosomes or missing single chromosomes 2N + 1 2N - 1 Suffix: “-somy” or “-somic” 2N + 1 = trisomy 2N - 1 = monosomy 2N + 2 = tetrasomy

28. Generally arise through non-disjunction at meiosis homologues or chromatids do not separate gametes contain 2 or no copies of one chromosome

30. Most aneuploidies in humans lead to such drastic effects, the fetus is spontaneously aborted early in development A few survive ‘til birth; some beyond

31. 47, +21 1/700 live births over 60% of conceptions aborted spontaneously 20% stillborn incidence increases sharply w/ maternal age 1/300 for 35 year olds 1/22 for 45 year olds

32. characteristic facial appearance small nose, flat face, epicanthal fold single palmar crease mental retardation (avg. IQ < 50) multiple complications heart disease leukemia epilepsy some fertility

33. 47; +18 1/8000 live births; maternal age affect low birth weight multiple dysmorphic features chin, ears, single palmar crease, clenched hands malformations of the brain, heart, kidneys, and other organs rarely survive beyond 1 year

34. 47; + 13 1/20,000 live births; maternal age effect multiple dysmorphic features micropthalmia, cleft palate, clenched fists, polydactyly, ears and scalp abnormal… heart defects; systemic defects…. 50% die in first month; rarely survive beyond 1 year

35. 1/500 live male births (?) often asymptomatic except for sterility, learning disabilities small testes; low testosterone levels poorly developed male 2 o sexual charact. some female characteristics: enlarged breasts, elongated limbs, increased incidence of “female” diseases: breast cancer, scoliosis, osteoporosis hormone therapy improves symptoms

36. 1/1000 live male births? formerly called “criminal chromosome” 99% asymptomatic, though high incidence in penal institutions for the mentally subnormal (20/1000) lower than average intelligence? (learning disabilities) above average height, tendency to severe acne

37. 1/2500 live female births generally asymptomatic ‘til puberty lack of 2 o sexual characteristics; amenorrhoea short stature; low hair line; heart disease, renal malformations, ovaries generally underdeveloped, sterile hormone therapy helpful

38. 1/700 live female births (?) generally asymptomatic 15 - 25% mildly mentally retarded some sterility

39. Changes in the numbers of genes deletions duplications Changes in the location of genes inversions translocations Robertsonian changes

40. Loss of a (generally small) segment of chromosome A B C D E F G A B D E F G C

41. Arise through spontaneous breakage some chromosomes have fragile spots radiation, UV, chemicals, viruses may increase breakage

42. May arise through unequal crossing over A B C D E F G A B C D E F G x A B C D E F F G A B C D E G Deletion Duplication

43. Large deletions will most probably be lethal Smaller deletions may allow survival E. coli : deletions of up to 1% have been observed in living cells D. melanogaster : deletions of up to 0.1% observed

44. Cri-du-chat syndrome Micro deletion of chromosome 5 DiGeorge syndrome Micro deletion of chromosome 22 Angelman syndrome Micro deletion of chromosome 15 Prader-Willi syndrome Micro deletion of chromosome 15

45. lack of muscle tone in newborn poor swallowing reflex as adult - gross obesity mean I.Q. ~ 50 microdeletion of 15 developmentally delayed jerky movements stiff, fixed smile uncontrolled laughter abnormal E.E.G., epilepsy microdeletion of 15 Prader-Willi Angelman

46. Redundant segment of a chromosome A B C D E F G A B C D E F F G

48. 180 o reversal of chromosome segment A B C D E F G H I J K A B C H G F E D I J K 180 O

49. Produced through breakage and reassociation of chromosome A B C D E F G

50. Produced through breakage and reassociation of chromosome A B C D E F G

53. May change phenotype through “position effects” move active genes to sites generally inactive; lose gene function move inactive genes to sites generally active; gain gene function May act to preserve blocks of genes (specific alleles) which function well together

54. Exchange of segments between non-homologous chromosomes F A B C D E L M N O P Q

55. A B C D E F O N M L Q P Remember: There are still two normal chromosomes in the cell! = translocation heterozygote

56. Translocation

57. Balanced Unbalanced Lead to impaired fertility complications to synapsis and segregation May lead to changes in phenotype position effects human cancers and translocations

58. Several human cancers are associated with reciprocal translocations Chronic myelocytic leukemia, many acute leukemias Philadelphia chromosome Burkitt’s lymphoma three translocations

59. All these involve oncogenes oncogenes: genes involved in cell proliferation normally active only at specific times embryonic/fetal development, etc. shut off under normal conditions

60. Reciprocal translocation between chr. 22 and chr. 9 9 9 22 22

61. Reciprocal translocation between chr. 22 and chr. 9 9 9 22 22 Chr. 9 segment has an oncogene; when moved, it becomes active

62. Translocations between chr. 8 and one of three others: 8 & 2 or 8 & 14 or 8 & 22 Chr. 8 has an oncogene Chr. 2, 14, 22 have genes coding for antibody production and their enhancer genes Oncogene becomes highly active under control of enhancers!

63. Fusions two chromosomes join to form one Fissions one chromosome splits to form two

64. Roberstsonian translocations

65. Familial Down Syndrome fusion of chromosomes 14 and 21 14 21 14+21 Carrier; phenotypically normal produces normal, carrier, and Down syndrome children

66. synapsis Three possible disjunctions

68. X X

69. X X X X

70. © 2007 Paul Billiet ODWS Images believed to be in the Public Domain 23 unpaired chromosomes 23 unpaired chromosomes 23 unpaired chromosomes 23 unpaired chromosomes Fertilisation Child Father 23 pairs of chromosomes Sex cells Meiosis Mother 23 pairs of chromosomes 23 pairs of chromosomes

71. A special type of cell division Used to make sex cells Meiosis halves the numbers of chromosomes Meiosis picks one chromosome from each pair at random and places them in a sex cell. This results in enormous variation amongst the sex cells. © 2007 Paul Billiet ODWS

72. Y X X X Fertilisation Possible children Father Sex cells Meiosis Mother XX XY Chance of a girl 50% Chance of a boy 50% © 2007 Paul Billiet ODWS X Y X XX XY X XX XY

73. The sex of many animals is determined by genes but on chromosomes called sex chromosomes The other chromosomes are called autosomes One sex is homogametic The other sex is heterogametic © 2007 Paul Billiet ODWS

74. © 2007 Paul Billiet ODWS HOMOGAMETIC SEX HETEROGAMETIC SEX SEX DETERMINATION Female XX Male XY Presence of Y-chromosome = maleness (mammals and fish) Presence of second X-chromosome = femaleness (Drosophila, the fruit fly) Male ZZ Female ZW Birds, amphibians, reptiles, butterflies, moths. Female XX Male Xo Grasshoppers

75. Constant for each cell in the body (except sex cells which only have half sets). Constant throughout the life of an individual (you don’t lose or gain chromosomes) Constant for all members of a species © 2007 Paul Billiet ODWS

76. Mouse Maize © A. Lane Rayburn Image believed to be in the Public Domain

77. © 2007 Paul Billiet ODWS Organism Chromosome numbers Human 46 Chimpanzee 48 House Mouse 40 Maize 20

78. Image believed to be in the Public Domain