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J a v a d J a m s h i d i
F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s , D e c e m b e r 2 0 1 5
S e s s i o n 1Genetics
The Cellular and MolecularBasis ofInheritanceandChromosomes
2
CellNucleusCytoplasm
DNACompositionStructureReplicationTranscription
Chromosomes
Components of Inheritance
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Cell Cycle / Mitosis
Image from: An Introduction To Human Molecular Genetics Second Edition by Jack J. Pasternak, Published by John Wiley & Sons, Inc., Hoboken, New Jersey 2005.
4
Meiosis
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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The Human Genome
The nuclear genomeApproximately 3 200 000 000 nucleotides of DNAEither 23 or 24 different types of chromosomal DNA MoleculesAbout 20 000 to 23 000 genes, or maybe less!
The mitochondrial genome16 569 nucleotidesA small circular DNA37 genes
Human genes
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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)
Mitochondrial DNA
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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
Mutations
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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
Types of Mutation
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Substitution
Deletion
Insertion
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What do
Chromosomes do?
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Chromosome Structure
p arm
q arm
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Chromosomes Morphology
Classified according to position of centromere
Metacentric: Central centromere
Acrocentric:Sub-terminal centromere
Submetacentric: Intermediate centromere
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Prepare a Karyotype
Image from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)
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Karyotype
15 Imag
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A B
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Chromosome Nomenclature
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Karyotype Report
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)
Meiosis
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The Consequences of Meiosis
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 223, or approximately 1 in 8 million
Crossing over, each chromatid contains portions of DNA from both parental homologous chromosomes
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Chromosome Abnormality
Numerical
Aneuploidy
MonosomyTrisomyTetrasomy
PolyploidyTriploidyTetraploidy
StructuralTranslocations
ReciprocalRobertsonian
DeletionsInsertionsInversions
ParacentricPericentric
RingsIsochromosomes
Different Cell Lines (Mixoploidy)MosaicismChimerism
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Numerical Abnormalities
Aneuploidy: loss or gain of one or more chromosomes
Trisomy, Tetrasomy
Monosomy
Polyploidy: addition of one or more complete haploid complements
Triploidy
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Trisomy
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
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Monosomy
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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Non-disjunction
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Structural Abnormalities
Result from chromosome breakage
Balanced: no loss or gain of genetic materialgenerally 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.
Robertsonian translocations
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What did you learn?
DNA , Genes and Inheritance
Chromosomes
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