Lecture 2-3Genetics

Dr. Heba Al-Fares1

Contents of this lectureChromosome structureClassification of chromosomesChromosomal aberrations

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chromosomes in prokaryotic and eukaryotic cellChromosomes are structures within the living cells that

contain the genetic material.In ProkaryoticChromosomes is circular DNA molecules contain the

entire set of genetic instruction essential for life of the cell. (in a region of the cytoplasm called the nucleoid).

When circular DNA copied, the genetic information is passed on to the daughter cells (new cells created by cell division) during mitosis.

In EukaryotesChromosomes are threadlike strands that are consisting

of chromatin and carrying the genetic information arranged in a linear sequence.

To pass genetic traits from one generation to the next, the chromosomes must be copied, and then the copies must be divided up.

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Chromosomes (DNA) in eukaryotics• Chromosomes are double helix spirals

composed of deoxyribonucleic acid (DNA).

• Each contains genes in a linear order.

• Human body cells contain 46 chromosomes in 23 pairs – one of each pair inherited from each parent

• Chromosome pairs 1 – 22 are called autosomes.

• The 23rd pair are called sex chromosomes: XX is female, XY is male.

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Chromosome Structure DNA is long and thin and fragile:

needs to be packaged to avoid breaking.

First level is the nucleosome, 200 bp of DNA wrapped twice around a core of 8 histone proteins (small and very conserved in evolution). A string of beads.

The nucleosomes coil up into a 30 nm chromatin fiber. This level of packaging exists even during interphase.

During cell division, chromatin fibers are attached in loops of variable size to a protein scaffold. The DNA probably attaches at specific AT-rich areas called scaffold attachment regions.

The loops may be functional units: active vs. inactive in transcription.

Further coiling gives the compact structures we see in metaphase.

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Centromeres Sometimes called the “primary

constriction” on a chromosome, based on microscopic appearance.

The centromere is the attachment point for the spindle.

The centromere is a region of DNA on the chromosome. During cell division, a large protein structure, the kinetochore, that attaches to the centromere DNA sequences. The spindle proteins then get attached to the kinetochore.

The centromere is many repeats of about 170 bp element .

Centromere regions also contain large amounts of repeated sequence DNA.

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Telomeres

Telomeres are the DNA sequences at the ends of chromosomes. Chromosomes that lose their telomeres often fuse with other chromosomes or become degraded. There are telomere-binding proteins that protect the chromosome ends.

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Euchromatin and HeterochromatinEuchromatin is the location of active

genes (although many genes in euchromatin are not active: depends on cell type). During interphase euchromatin is extended and spread out throughout the cell.

Heterochromatin is darkly staining, condensed, and late replicating. Genes in heterochromatin are usually inactive.

Some heterochromatin is constitutive : always heterochromatin: especially around centromeres. Composed mostly of repeat sequence DNA.

Other heterochromatin is facultative: can be heterochromatin or euchromatin

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Microscopic examination of chromosomes• Karyotype : the chromosome as viewed under the

microscope (nuclear type).• Cytogenetics : the microscopic study of chromosomes and

analysis of their genetic property it combine genetic and cytology.

• It describes the light microscopic morphology of the component chromosomes, so that their relative lengths, centromere positions, and secondary constrictions can be identified.

CYTOGENETICS

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Classification of chromosomesMain features to identify and classify

chromosomes1. Size2. Location of the centromeres3. Banding patterns

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Banding patternsG-banding: chromosomes are treated with

trypsin enzyme that partially digest chromosomal proteins when exposed to dye call Giemsa some chromosomal region bind the dye heavily and produce dark band (tightly compacted and G bands contain high proportion of A-T pairs).

R (reverse Giemsa) bands are produced by heat-treating the chromosomes in saline solution before staining with Giemsa (the R bands rich in G-C and most active gene are located in this bands)

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Figure 8.1

Chromosome sizeLarge chromosomesMedium chromosomesSmall chromosomesSex chromosomes

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Types of ChromosomeChromosomes are placed into broad

categories depending on the position of the centromere.

metacentric: centromere in the middle, with arms of equal length.

telocentric: centromere at one end, with only 1 arm.

acrocentric: centromere near one end, with arms of very different lengths

sub-metacentric: centromere near the middle, with arms of slightly different lengths.

Chromosome are classified based on the locations of their centromeres.

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Counting out chromosome numbersEach eukaryotic organism has a very specific

number of chromosomes per cell — ranging from one to many. For example, humans have 46 total chromosomes.

These chromosomes come in two varieties: Sex chromosomes: These chromosomes

determine gender. Human cells contain two sex chromosomes. If you’re female, you have two X chromosomes, and if you’re male, you have an X and a Y chromosome.

Autosomal chromosomes: Autosomal simply refers to non-sex chromosomes. So, sticking with the human example, humans have 44 autosomal chromosomes.

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Counting out chromosome numbersIn humans, chromosomes come in pairs. That means you have 22 pairs of uniquely

shaped autosomal chromosomes plus 1 pair of sex chromosomes, for a total of 23 chromosome pairs.

Your autosomal chromosomes are identified by numbers — 1 through 22.

So, you have two chromosome 1s, two 2s, and so on.

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Counting out chromosome numbersThis figure

shows you how all human chromosomes are divided into pairs and numbered.

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Homologous chromosomes When chromosomes are divided into pairs, the

individual chromosomes in each pair are considered homologous, meaning that the paired chromosomes are identical to one another in shape and size.

These homologous chromosomes are sometimes referred to as homologs for short.

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Chromosomes carry genes Genes are sections of DNA that make up the

building plans for physical traits. The genes tell the body how, when, and where to

make all the structures that are necessary for the processes of living.

Each pair of homologous chromosomes carries the same — but not necessarily identical — genes.

For example, both chromosomes of a particular homologous pair might contain the gene for hair color, but one can be a “brown hair” version of the gene — alternative versions of genes are called alleles — and the other can be a “blond hair” allele.

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Chromosomes carry genes One chromosome carries the allele A while its

homolog carries the allele a (the relative size of an allele is normally very small; the alleles are large here so you can see them).

The alleles code for the different physical traits (phenotypes) you see in animals and plants like hair color or flower shape.

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Chromosomes carry genesEach point along the chromosome is called a

locus (Latin for “place”). The plural of locus is loci (pronounced low-sigh).

Most of the phenotypes that you see are produced by multiple genes (that is, genes occurring at different loci and often on different chromosomes) acting together.

For instance, human eye color is determined by at least three different genes that reside on two different chromosomes.

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Chromosome numbers haploid and euploidChromosome numbers can get a bit confusing. Humans are diploid, meaning we have two

copies of each chromosome. Some organisms (like bees and wasps) have

only one set of chromosomes (cells with one set of chromosomes are referred to as haploid); others have three, four, or as many as sixteen copies of each chromosome!

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Chromosome numbersThe number of chromosome sets held by a

particular organism is called the ploidy. The total number of chromosomes doesn’t tell

you what the ploidy of an organism is. For that reason, the number of chromosomes

of an organism is often listed as some multiple of n.

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Chromosome numbersHumans are 2n = 46 (indicating that humans

are diploid and the total number of chromosomes is 46).

A single set of chromosomes referred to by the n is the haploid number. Human sex cells such as eggs or sperm are haploid.

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Chromosome number and ploidy condition in commercial important crop species

Common name

Chromosome no. in X

2nPloidy

alfalfa8324X

Apple17342X

Oats 13524X

Wheat, durum

7284X

Wheat, bread

7426X

Barley 7142X

Strawberry

7568X

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X : (genome) The entire complement of genetic material in chromosome set. N: basic number of chromosome

Variation In Chromosome NumberEuploidy

Normal variations of the number of complete sets of chromosomesChromosomes number are multiples of some basic number (n)N: number of chromosome in one nuclear genome (haploid) that is

1xn=n, diploid 2n that is 2xn=2n, and so onN is called the haploid chromosome number.2n is called diploid. 3n, 4n, and so on are called polyploid.Haploid, Diploid, Triploid, Tetraploid, etc…Genome (X): The entire complement of genetic material in

chromosome set.

AneuploidyVariation in the number of particular chromosomes within a set

Aneuploidies: changes in part of chromosome setsA change from euploid numberMonosomy, trisomy, tetrasomy

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Polyploidy v Aneuploidy

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Plants commonly exhibit polyploidy 30-35% of ferns and flowering plants are polyploid Many of the fruits & grain are polyploid plants

Polyploid strains often display desirableagricultural characteristics wheat cotton strawberries bananas

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Euploid Number can Naturally Vary

Most animal species are diploidPolyploidy in animals is generally lethalSome naturally occurring euploidy variations

bees - females are diploid.

Benefit of Odd Ploidy-Induced Sterility

Seedless fruitwatermelons and bananasasexually propagated by human via cuttings

Seedless flowersMarigold flowering plants

Prevention of cross pollination of transgenic plants

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Chromosomal aberrations Substantial changes in chromosome structureTypically affect multiple genes (loci)

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CATEGORIES OF CHROMOSOMAL ABERRATIONS

InversionsNormal A B C D E F

Pericentric – inversion about the centromere A D C B E F

Paracentric – inversion not involving the centromere

A B C E D F

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A segment of chromosome that is flipped relative to that in the homologue

Inversions

Figure 8.11

Centromere lies within inverted region

Centromere lies outside

inverted region

DeletionsLoss of a region of a chromosome

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Symptom: cat-like cry, short stature, and facial abnormality.

Duplication

Duplications result from doubling of chromosomal segments, and occur in a range of sizes and locations.

a. Tandem duplications are adjacent to each other.

b. Reverse tandem duplications result in genes arranged in the opposite order of the original.

c. Tandem duplication at the end of a chromosome is a terminal tandem duplication.

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Fig. 17.5 Duplication, with a chromosome segment repeated

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DUPLICATION, WITH A CHROMOSOME SEGMENT REPEATED

Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

Forms of chromosome duplications are tandem, reverse tandem, and terminal tandem duplications

39Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

Phenotypic consequences of duplications correlated to size & genes involved

Duplications tend to be less detrimental

Duplications

When a segment of one chromosome becomes attached to another

Exchange or joining of regions of two non-homologous chromosomes

In reciprocal translocations two non-homologous chromosomes exchange genetic material

Usually generate so-called balanced translocations Usually without phenotypic consequences.

Translocations

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FIG. 8.13B(TE ART)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Nonhomologous chromosomes

Reciprocaltranslocation

1 1 7 7

Nonhomologous crossover

1 7

Crossover betweennonhomologous

chromosomes

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FIG. 8.13A(TE ART)

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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Environmental agent causes 2 chromosomes

to break.

Reactive ends

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2 2

DNA repair enzymesrecognize broken ends

and connect them.

Chromosomal breakage and DNA repair

ChromosomesProkaryoticCircularVery small1 chromosome per cellSome enzymes and

proteins are associated with the DNA.

Not housed in a nucleus.

EukaryoticLinearFairly longSeveral

chromosomes per cell.

Histone proteins package DNA Same in all eukaryotes

Housed in a nucleus.Nucleosome—2

loops of DNA wrapped around 8 histone proteins.