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

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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.

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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

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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