Javad Jamshidi Fasa University of Medical Sciences, December 2015 Session 1 Genetics The Cellular and Molecular Basis of Inheritance and Chromosomes

2 Cell Nucleus Cytoplasm DNA Composition Structure Replication Transcription Chromosomes

3 Image from: An Introduction To Human Molecular Genetics Second Edition by Jack J. Pasternak, Published by John Wiley & Sons, Inc., Hoboken, New Jersey 2005.

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5 The nuclear genome Approximately nucleotides of DNA Either 23 or 24 different types of chromosomal DNA Molecules About to genes, or maybe less! The mitochondrial genome nucleotides A small circular DNA 37 genes

6 Most human genes are unique single-copy genes coding for polypeptides Include enzymes, hormones, receptors, and structural and regulatory proteins. Image from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)

7 The mtDNA genome is very compact, containing little repetitive DNA Codes for 37 genes, which include Two types of ribosomal RNA 22 transfer RNAs 13 proteins Inherited almost exclusively from the oocyte leading to the maternal pattern of inheritance

8 Heritable alteration or change in the genetic material Can arise through exposure to mutagenic agents, but the vast majority occur spontaneously through errors in DNA replication and repair. Somatic mutations & Germ line mutation It is estimated that each individual carries up to six lethal or semilethal recessive mutant alleles

9 Substitution Deletion Insertion

10 What do Chromosomes do?

11 p arm q arm

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

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

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

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17 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)

18 Meiosis

19 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

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

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

22 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

23 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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25 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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 DNA, Genes and Inheritance  Chromosomes