GENETIC MUTATIONSDec 5, 2013

• Let’s review what we’ve done so far!

What Exactly is a chromosome?

Chromosomes are the rod-shaped, filamentous bodies present in the nucleus, which become visible during cell division.

They are the carriers of the gene or unit of heredity.

Number of chromosomes

• Normally, all the individuals of a species have the same number of chromosomes.

• Closely related species usually have similar chromosome numbers.

• Presence of a whole sets of chromosomes is called euploidy.

• It includes haploids, diploids, triploids, tetraploids etc.

• Gametes normally contain only one set of chromosome – this number is called Haploid

• Somatic cells usually contain two sets of chromosome - 2n : Diploid

3n – triploid4n – tetraploid

The condition in which the chromosomes sets are present in a multiples of “n” is Polyploidy

When a change in the chromosome number does not involve entire sets of chromosomes, but only a few of the chromosomes - is Aneuploidy.

• Monosomics (2n-1)• Trisomics (2n+1)• Nullisomics (2n-2)• Tetrasomics (2n+2)

• In a species Karyotype, a pictorial or photographic representation of all the different chromosomes in a cell of an individual, chromosomes are usually ordered by size and numbered from largest to smallest.

Centromeres and Telomeres• Centromeres and telomeres are two

essential features of all eukaryotic chromosomes.

• Each provide a unique function i.e., absolutely necessary for the stability of the chromosome.

• Centromeres are required for the segregation of the centromere during meiosis and mitosis.

• Teleomeres provide terminal stability to the chromosome and ensure its survival

• Chromosomes may differ in the position of the Centromere, the place on the chromosome where spindle fibers are attached during cell division.

• In general: – near the middle = metacentric– toward one end = acrocentric or

submetacentric– very near the end = telocentric.

*** Karyotype activity

• The centromere divides the chromosome into two arms, so that, for example, an acrocentric chromosome has one short and one long arm,

• While, a metacentric chromosome has arms of equal length.

• All house mouse chromosomes are telocentric, while human chromosomes include both metacentric and acrocentric, but no telocentric.

Prokaryotes vs Eukaryotes• Eukaryotes= true nucleus• Prokaryotes= unicellular organisms• Not only the genomes of eukaryotes are more

complex than prokaryotes, but the DNA of eukaryotic cell is organized differently from that of prokaryotic cells.

• The genomes of prokaryotes are contained in single chromosomes, which are usually circular DNA molecules.

• In contrast, the genomes of eukaryotes are composed of multiple chromosomes, each containing a linear molecular of DNA.

Raveled vs Unraveled DNA

Genetic Mutations

Structural

Nondisjunction

Chromosomal Aberrations

Human Karyotype

Normal Female Karyotype

Normal Male Karyotype

Chromosome Structure- Idiotype

Would this have helped you with your activity?

Structural Mutations

• Point mutations:NonsenseSilentMissense Deletion Insertion

• Deletions• Insertions• Duplications• Translocations

Insertions and Deletions (Indels)• Extra base pairs may be added

(insertions) or removed (deletions) from the DNA of a gene.

• The number can range from one to thousands. Collectively, these mutations are called indels.

•CAT• CART

• CHAT

• SCAT

• AT

• CATS

• CATHY

• CA

• A

• Indels of three nucleotides or multiples of three may be less serious because they preserve the reading frame.

• However, a number of inherited human disorders are caused by the insertion of many copies of the same triplet of nucleotides. – Huntington's disease and the fragile X

syndrome are examples of such trinucleotide repeat diseases.

Deletions

• Removal of sections of a chromosome will affect more than one gene and thus more than one protein…..

• Sections that have been deleted from one chromosome may become inserted into another.– Where the new segment is inserted affects

the outcome for the recipient chromosome.– CAT vs HIVE

= AT & CHIVE

Inversions occur within a single chromosome

Picking up where we left off…

• Yesterday we talked about indels

• Snowball activity!

Duplications• Duplications are a doubling of a section of

the genome.

• Gene duplication has been implicated in several human neurological disorders.

• Gene duplication has occurred repeatedly during the evolution of eukaryotes.

• Genome analysis reveals many genes with similar sequences in a single organism.

Such gene duplication can be beneficial:

1.Over time, the duplicates can acquire different functions. – This can provide the basis for adaptive evolution.

2.Genes that are similar in sequence and function, provide redundancy. – If one gene is “damaged” the redundant one can take

over.

Translocations• Translocations are the transfer of a piece of one

chromosome to a nonhomologous chromosome.

• Translocations are often reciprocal; that is, the two nonhomologues swap segments.

Translocations can alter the phenotype in several ways:

• translocated genes may have their expression altered.

• the break may occur within a gene destroying its function.

• the breakpoint may occur within a gene creating a hybrid gene.

• Look up an article on hybrid genes with the title: “Humans evolved after a female chimpanzee mated with a pig”

• On an exit card to be passed in, write down:– The source of the article (website name)– 2 things that you believe are legitimate facts from the theory– At least 2 questions/concerns you have about the theory

• When/if finished, check out this website & complete the questions with it:

http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter15/changes_in_chromosome_structure.html

• If you finish all of this, please start working on the handout “Chromosome Mutations and Chromosomal Disorders”

Nondisjunction

Monosomy

Trisomy

Chromosomal Aberrations

Mutations

• In the living cell, deoxyribonucleic acid (DNA) undergoes frequent chemical change, especially when it is being replicated.

• Most of these changes are quickly repaired. Those that are not, result in a mutation. Thus, mutation is a failure of DNA repair.

http://science.jrank.org/pages/4529/Mutagen.html

Mutagens

• Mutagens are chemicals or physical factors (such as radiation) that increase the rate of mutation in the cells of bacteria, plants, and animals (including humans).

• Most mutagens are of natural origin and are not just a modern phenomenon.

• Mutagens can be found in the food we eat, the air we breath, or the ground we walk on.

• Very small doses of a mutagen usually have little effect while large doses of a mutagen could be lethal.

How do mutagens affect us?• DNA in the nuclei of all cells encodes

proteins, which play important structural and functional (metabolic) roles in the cell.

• Mutagens typically disrupt the DNA of cells, causing changes in the proteins that the cell produces, which can lead to abnormally fast growth (cancer), or even cell death.

• In rare incidences, mutagens can even cause protein changes that are beneficial to the cell.

HOW IT HAPPENS• When cells are exposed to a mutagen, breaks

are produced in the chromosomes• Broken ends appear to be ‘sticky’ and can rejoin

with any other sticky end• Once breaks are produced, different fragments

may behave in a variety of ways• Breaks may rejoin in their original configuration• Breaks may fail to rejoin and give rise to a deletion • Broken ends may resort and rejoin other broken

ends and give rise to chromosomes that appear to be grossly distorted

TYPES OF ABERRATIONS2 CLASSES:

1. Chromosome Aberrations - result if cell is irradiated early in interphase (G1), before chromosome material has been duplicated - during DNA synthetic phase that follows, this strand of chromatin lays down an identical strand next to itself

2. Chromatid Aberration - result if cell is irradiated later in interphase after DNA has doubled (G2)

and chromosome consist of 2 strands of chromatin - break that occurs in a single chromatid arm, leaves opposite arm of same

chromosome undamaged

EXAMPLES OF ABBERATIONS

Many types of aberrations and rearrangements are possible:

• 3 Types are lethal to the cell» Dicentric, » Centric Ring (chromosome aberrations) and » Anaphase Bridge (chromatid aberration)

• 2 Important Non-Lethal Rearrangements» Symmetric translocations and small deletions

(interstitial and terminal)» Associated with several human malignancies via

activation of oncogenes or loss of suppressor genes

LETHAL ABERRATIONS

All 3 represent gross chromosomal distortions:

• Dicentric (or Tricentric)

• Involves interchange between 2 separate

chromosomes• If break occurs in each one early in interphase and

sticky ends are close together they may join• this interchange is replicated during DNA synthesis and

results in a distorted chromosome with 2 (or 3) centromeres and an acentric fragment

DICENTRIC CHROMOSOME

From: Radiobiology for the Radiologist, pg 24

From: Radiobiology for the Radiologist, pg 25

• Centric Ring• Break induced by radiation in each arm

of a single chromatid early in cell cycle

• The sticky ends may rejoin to form a ring with a centromere and an acentric fragment

• Later during DNA synthetic phase the chromosome is replicated

CENTRIC RING

From: Radiobiology for the Radiologist, pg 24

From: Radiobiology for the Radiologist, pg 26

• Anaphase BridgeResults from breaks that occur late in cell cycle (G2), after chromosome has replicated

Breaks may occur in both chromatids of the same chromosome, sticky ends may rejoin incorrectly to form a sister union

At anaphase, when the 2 sets of chromosomes move to opposite poles, the section of chromatin between the centromeres is stretched across between the poles, hindering separation into new daughter cells

Difficult to see in human cell cultures since bridge is only evident at anaphase

ANAPHASE BRIDGE

From: Radiobiology for the Radiologist, pg 24

From: Radiobiology for the Radiologist, pg 27

• Symmetric Translocation

• Involves break in 2 pre-replication chromosomes, with broken ends being exchanged between the 2 chromosomes

• Divided into pericentric (includes centromere) and paracentric (confined to 1 chromosome arm) inversions

• A translocation is associated with several human malignancies by the activation of an oncogene (e.g. Burkitt’s lymphoma)

• Small Deletion • Terminal deletion:

» Loss of genetic material from end of chromatid

• Interstitial deletion» Minute: very small deletion; show as small paired dots» Acentric ring: larger interstitial deletion; show as

acentric rings

– Deletion may be associated with carcinogenesis (cancer growth) if loss of material includes a suppressor gene

From: Biological Dosimetry, pg 18

• The Mighty Mutation Maker