Javad Jamshidi Fasa University of Medical Sciences, October 2014 Session 3 Medical Genetics Chromosomes And Cell division

2 What do Chromosomes do?

3 p arm q arm

4 Classified according to position of centromere Metacentric: Central centromere Acrocentric: Sub-terminal centromere Submetacentric: Intermediate centromere

5 Autosomes are numbered from largest to smallest, except that chromosome 21 is slightly smaller than chromosome 22

6 Image from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012) A B C DE F G

7 Karyotype Analysis G banding Q banding R banding C banding Molecular Cytogenetics FISH CGH Array CGH

8 Image from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)

9 Is used most commonly. Approximately 400 to 500 bands per haploid set. Each band corresponds on average to approximately 6 to 8 Mb High-resolution banding, up to 800 bands per haploid set

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11 Q banding Similar pattern to G banding, Needs fluorescent microscope R banding Light and dark bands are reversed C banding Used to identify centromeres / heterochromatin

12 Based on the ability a single-stranded DNA to anneal with its complementary target DNA probe is labeled with a fluorochrome Has been widely used for clinical diagnostic and there are a number of different types of probes

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14 Spectral karyotyping (SKY)

15 For detection of regions of allele loss and gene amplification Useful in study tumors

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17 Image from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)

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20 Normal male 46,XY Normal female 46,XX A male with Down syndrome 47,XY,+21 female with cri du chat syndrome 46,XX,del(5p)

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22 Meiosis

23 It facilitates halving of the diploid number of chromosomes Provides an extraordinary potential for generating genetic diversity bivalents separate independently, likelihood of two gametes with the same chromosomes is 1 in 2 23, or approximately 1 in 8 million crossing over, each chromatid contains portions of DNA from both parental homologous chromosomes

24 Table from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)

25 Numerical Aneuploidy Monosomy Trisomy Tetrasomy Polyploidy Triploidy Tetraploidy Structural Translocations Reciprocal Robertsonian Deletions Insertions Inversions Paracentric Pericentric Rings Isochromosome s Different Cell Lines (Mixoploidy) Mosaicism Chimerism

26 Aneuploidy: loss or gain of one or more chromosomes Trisomy, Tetrasomy Monosomy Polyploidy: addition of one or more complete haploid complements Triploidy

27 Autosomal trisomies compatible with survival to term: Down syndrome (trisomy 21) Patau syndrome (trisomy 13) Edwards syndrome (trisomy 18) Most other autosomal trisomies result in early pregnancy loss An additional sex chromosome (X or Y) has only mild phenotypic effects

28 The absence of a single chromosome Autosomal monosomy is almost always incompatible with survival to term Monosomy of sex chromosome is viable, Turner syndrome 45,X

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30 Polyploid cells contain multiples of the haploid number of chromosomes such as 69, triploidy, or 92, tetraploidy Survival beyond mid-pregnancy is rare. Triploidy is found relatively often in spontaneous miscarriages

31 Origins of triploidy

32 Result from chromosome breakage Balanced: no loss or gain of genetic material generally harmless, but some exceptions carriers are at risk of producing children with an unbalanced chromosomal complement. Unbalanced: contains an incorrect amount of chromosome material The clinical effects are usually serious.

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What did you learn?  Chromosomes  Structure  Nomenclature  Classification  Methods of Chromosome Analysis  Karyotype  Fish  Chromosome abnormalities  Numerical  Structural