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Cell Reproduction: Mitosis & Meiosis. Chapter 8 (and the beginning of Chapter 10). Overview. DNA replication Overview of cell division Mitosis Meiosis. DNA Replication. Occurs during interphase of cell cycle 1 DNA molecule untwisted

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Cell Reproduction: Mitosis & Meiosis

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Cell reproduction mitosis meiosis l.jpg

Cell Reproduction: Mitosis & Meiosis

Chapter 8

(and the beginning of Chapter 10)


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Overview

  • DNA replication

  • Overview of cell division

  • Mitosis

  • Meiosis


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DNA Replication

Occurs during interphase of cell cycle

1 DNA molecule untwisted

Each parent strand serves as template for new strand

= 2 new DNA molecules,

each ½ old & ½ new

= semi-conservative replication


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Enzymes break H bonds between 2 strands

= unwinds & exposes nucleotide bases

Free nucleotides pair with exposed bases

Each parent strand has new one made on it

= twist together to form double helix


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DNA replication in a little more detail …

Sugar-phosphate backbones of 2 DNA strands run in opposite directions

5’ end

= Phosphate group on sugar’s C

3’ end

= –OH group on sugar’s C


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DNA polymerase adds nucleotides to 3’ ends only

Daughter strand grows in 5’ to 3’ direction

= 1 daughter strand synthesized continuously

= Other daughter strand synthesized disjointedly


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Replication Enzymes: Helicases

Catalyze breaking of H bonds so double helix can unwind

Work with small proteins to prevent rewinding of parent strands


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Replication Enzymes: DNA Polymerases

Catalyze addition of free nucleotides to exposed bases on each strand

Also have proofreading abilities


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Replication Enzymes: DNA Ligases

Work on discontinuously-assembled strand

Seal together short stretches of new nucleotides


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Transcription

Only part of DNA strand unwound

RNA polymerase adds nucleotides to growing strand

Results in 1 free mRNA strand

DNA replication

Whole DNA molecule unwound

DNA polymerase adds nucleotides to growing strand

Results in 2 double-helix DNA molecules

Transcription vs. DNA replication


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Mistakes occur that can be lethal if not caught

e.g. wrong base-pairing

DNA proofreading mechanisms fix most replication errors & breaks in strands

(proofread & correct mismatches)

Repair enzymes repair some changes by snipping out damaged sites or mismatches

If mismatch can’t be fixed, replication is stopped


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Cell Division: An Overview

Parents reproduce to produce new generation of cells or multicellular organism

Offspring inherits all information & metabolic machinery from parent


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Prokaryotic Cell Division

Prokaryotic cells reproduce asexually

= binary fission


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Eukaryotic Cell Division

DNA in eukaryotic cells is in nucleus

Eukaryotic cells can’t divide by fission

Must copy & package DNA into > 1 nucleus before cytoplasm can split


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Two Types of Cell Division

Mitosis:

  • Produces 2 genetically identical cells

  • Happens throughout body

    Meiosis:

  • Produces 4 genetically different cells

  • Cells only have ½ of genetic info

  • Happens only in gonads


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Mitosis

One part of the cell cycle

Growth, cell replacement, tissue repair

Also used for asexual reproduction

= organisms clone selves

Unique to eukaryotes


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The Cell Cycle

The period from one cell division to next


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Interphase: The Longest Phase

90% of cell cycle length


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Interphase


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G1: Gap / Growth Phase

Cell growth

# of cytoplasmic components doubled


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S: Synthesis Phase

DNA duplicated


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Chromosome & copy = sister chromatids

Joined at centromere


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G2: Gap or Growth Phase II

Makes proteins necessary for cell division

Cell prepares to divide


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Cells stay in G1 if making macromolecules

Enter S when DNA & accessory proteins are copied

Rate of DNA replication is same for all cells of a species


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Same cycle length for same type of cells

Different cycle lengths for different types of cells

e.g. cells in red bone marrow divide every second

e.g. nerve cells stay in G1 indefinitely

Rate of cell division is under control

(checkpoints, molecular brakes, etc.)


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After G2, cell enters mitosis

Mitosis maintains cell’s chromosome #


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Chromosome Number

Humans have 46 chromosomes

= diploid (2n)

2 of each type of chromosome

= one set from mother, one from father


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During mitosis:

Each 2n parent cell produces two 2n daughter cells

Each daughter cell has each pair of chromosomes

= 23 pairs


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During mitosis, 2 sister chromatids (duplicated chromosomes) separate

Each becomes independent chromosome that ends up in 1 of daughter cells


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The Mitotic Spindle

Present in every cell

Made of microtubules

= change length by addition or removal of tubulin subunits

Originates from pair of centrioles


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Early in cell division, duplicated chromosome is condensed = coils up

DNA winds twice around histones

= nucleosome

Keeps chromosomes organized during nuclear division


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Late Interphase / Pre-Prophase

Outside of nucleus, 2 centrioles duplicate selves


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Early Prophase

Inside nucleus:

Chromosomes begin to condense

Outside nucleus:

Spindle begins to form

Nuclear envelope begins to fall apart


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Late Prophase

Nuclear envelope completely falls apart

Spindle fibres from each pole attach to sister chromatids of each chromosome


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Metaphase

Chromosomes line up halfway between spindle poles


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Anaphase

Sister chromatids of each chromosome separate & move to opposite poles

(motor proteins attached to kinetochores drag chromatids along microtubules)

Spindle poles pushed apart by growing microtubules


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Telophase

1 of each type of chromosome reaches each spindle pole

= 2 identical groups of chromosomes at each cell pole

Chromosomes decondense

Nuclear envelope forms around each cluster of chromosomes

= two nuclei, each with 2n # of chromosomes


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Cytokinesis

Cytoplasm of cell divides

Results in 2 daughter cells, each with same number of chromosomes as parent cell


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Cytokinesis in Animal Cells

Contractile ring mechanism

Halfway between cell’s poles, plasma membrane constricts = cleavage furrow

(ATP energy causes contraction of actin filaments)

Cleavage furrow deepens until cytoplasm split into 2


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Cytokinesis in Plant Cells

Cell plate formation

Golgi vesicles move to cell equator & fuse

Vesicle membranes become cell membranes

Contents become cellulose cell wall


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Summary of Mitosis

Nuclear & cellular division that maintains chromosome #

Used for growth, repair, asexual reproduction


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Cell division & DNA replication regulated so that:

DNA only replicated once before cell division

Cells that never divide do not replicate DNA

Cells don’t try to replicate DNA if lack the energy & raw materials to complete process


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Cellular Controls over Mitosis

Anchorage dependence

Animal cells must be in contact with a solid surface to divide

Density-dependent inhibition

Crowded cells stop dividing

Growth factors

Required to start & continue dividing

Secreted by other cells


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Cell Cycle Checkpoints

Cell cycle has checkpoints:

  • Structure of chromosomal DNA monitored

  • Completion of phases monitored

  • Determines if good time for cell division

    Rely on internal & external cues


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G1 checkpoint is most important:

If no go-ahead signal, cell will switch to non-dividing G0 phase

e.g. nerve & muscle cells remain in G0 indefinitely


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Cancer & Cell Division

  • If immune system doesn’t recognize & destroy a cancerous cell, it may divide multiple times & form a tumor

  • Benign

  • Cells remain localized

  • Malignant

  • Spreads to other parts of body & disrupts function


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Why don’t cancer cells follow the rules?

Don’t exhibit density-dependence

Have defective control systems

Ignore / over-ride checkpoints

Some synthesize own growth factors so continue dividing

Divide indefinitely


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Types of Cancers

Carcinomas

Internal & external coverings of body e.g. skin

Sarcomas

Supportive tissues e.g. bone & muscle

Leukemias & Lymphomas

Blood-forming tissues e.g. bone marrow, spleen, lymph nodes


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Ways to Treat Cancer

If not severe:

Surgical removal of tumor

Radiation therapy

(damages DNA of cancer cells to greater degree than normal cells)


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If severe:

Chemotherapy

Uses drugs to disrupt cell division

e.g. Paclitaxel freezes the mitotic spindle at metaphase

e.g. Vinblastin prevents spindle formation

Also affects rapidly-dividing normal cells e.g. intestinal lining, immune cells, hair follicle cells


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Cloning

Donor cells from 1 animal starved so enter non-dividing G0 phase

Nucleus removed from unfertilized egg cell of another animal


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Donor cell & egg cell placed next to each other in culture dish & electrically stimulated

Cells fuse & enter mitosis


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Cell continues mitotic divisions & forms embryo

Embryo implanted into surrogate mother

(same spp. as egg cell)

Surrogate mother gives birth to genetic twin of “donor cell” animal


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Mitosis vs. Meiosis

Mitosis:

  • Occurs in somatic cells

  • Results in 2 genetically identical cells

  • Growth, cell replacement, tissue repair

    = asexual reproduction

    Meiosis:

  • Occurs in sex cells

  • Results in 4 genetically different cells with ½ genetic info of parent cell

    = sexual reproduction


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Asexual vs. Sexual Reproduction

Asexual reproduction:

Individual makes multiple offspring with identical DNA

Sexual reproduction:

Allows for variety in heritable traits

Adaptive in changing environments

Meiosis → formation of gametes → fertilization


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The Eukaryotic Chromosome

Double-stranded DNA & associated proteins

Chromosomes duplicated during interphase

Unduplicated

Duplicated

Centromere

Sister chromatids


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Chromosome Number

Almost every cell in body has 2 complete sets of chromosomes

One set from mother, one from father

2 sets = diploid (2n)

Each cell has 2 versions of each gene


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Homologous chromosomes

Pair of chromosomes that carry genes for same heritable traits

Except sex chromosomes (X or Y)


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Genes

Sequences of chromosomal DNA

Contain heritable information to make new individuals

Individuals have pairs of genes on pairs of chromosomes

Each member of pair of gene = allele


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Allele

One of the variant forms of a gene at a particular (locus) location on a chromosome

Different alleles produce variation in inherited characteristics (e.g. hair & eye colour, etc.)

Basis for evolution: endless combinations of alleles lead to variations in traits


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So What is Meiosis?

Nuclear division that halves chromosome #

Occurs only in sex (reproductive) cells

1st step in formation of gametes ( or )

Gametes fuse with opposite sex gametes to form new individual


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Humans are diploid (2n) with 46 chromosomes

(23 + 23 homologous chromosomes)

Meiosis halves chromosome number so daughter cells (gametes) are haploid (n) with 23 chromosomes


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Gametes

Have only 1 set of chromosomes

= haploid(n)

Each gamete has 1 allele for each gene

In humans = eggs or sperm


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During meiosis, one cell goes through 2 divisions to end with formation of 4 cells, all with haploid (n) nuclei


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Interphase

Same as in mitosis:

Cell grows & duplicates cytoplasmic components

DNA is replicated


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Prophase I

Chromosomes condense

Crossing-over occurs between homologous chromosomes

Centrioles move to opposite sides of nuclear envelope

Nuclear envelope begins to fall apart


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Crossing Over

When chromosomes condense during prophase, homologous chromosomes stick very closely together & form a tetrad


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Maternal & paternal chromosomes swap genes

= exchange segments of genetic info

Homologous chromosomes become mixture of maternal & paternal info

chiasma


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Metaphase I

Homologues of chromosomes tethered by microtubules at opposite spindle poles

Chromosomes line up along equator of cell


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Anaphase I

Chromosomes pulled apart & move towards respective poles

Poles move further apart


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Telophase I

Cytoplasm divides

Results in 2 haploid cells

(only have 1 of each pair of homologous chromosomes)

Chromosomes still duplicated


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Prophase II

New mitotic spindle forms in each cell

Chromatids of each chromosome become tethered to opposite poles


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Metaphase II

Chromosomes line up along equator of cell


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Anaphase II

Chromatids separate & move towards opposite poles

Spindle poles pushed apart


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Telophase II

Nuclear envelope forms around each chromosome cluster


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Cytokinesis

Cytoplasm divides

Results in 4 haploid (n) daughter cells

Chromosomes are unduplicated


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Meiosis—things to pay attention to:

  • DNA replication:

    • Occurs only during interphase before Meiosis I

  • Meiosis I

    • Prophase: crossing-over

    • Metaphase: line up in 2 rows

    • Anaphase: separation of homologous chromosomes

  • Meiosis II

    • Similar to mitosis but no interphase precedes it

    • Division results in haploid cells


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Meiosis & Trait Variation

Can occur via:

  • Crossing over

  • Random alignment of chromosomes at metaphase I


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a. Crossing Over

Exchanges of allele-containing segments occurs between non-sister chromatids (i.e. between maternal & paternal chromosomes)

Gene-swapping: different versions of heritable information are swapped

= leads to recombination of genes & variation in traits


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b. Metaphase I Alignments

a.k.a random assortment

Duplicated chromosomes randomly tether to spindle poles

i.e. no set rules for where maternal & paternal chromosomes should be positioned


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Which half of homologous chromosome pair ends up at which pole is totally random

223 (8,388,608) possible combos of maternal & paternal chromosomes!


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From Gametes to Offspring

In animals, diploid germ cells become gametes

Gametes differ from species to species


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Male Gamete Formation

Germ cell (spermatogonium) develops into 1° spermatocyte

Enters meiosis

Results in 4 haploid cells (spermatids) that differentiate into sperm cells


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Female Gamete Formation

Germ cell (oogonium) develops into 1° oocyte (immature egg)

Grows in size

4 daughter cells differ in structure & function


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When 1° oocyte divides after meiosis I, one daughter cell (2° oocyte) gets most of cytoplasm

Other cell (1st polar body) is very small


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After meiosis II, one of 2° oocyte’s daughter cells is 2nd polar body (also very small)

Other gets most of cytoplasm and develops into ovum (egg)

1st polar body’s daughter cells are both polar bodies


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Polar bodies eventually degenerate

Sole function: to ensure ovum is haploid

Ovum gets most of cytoplasm & metabolic machinery

Is able to support early cell divisions of new individual after fertilization


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Fertilization: When 2 Gametes Become 1

Male & female gametes unite

Haploid nuclei fuse

Restores diploid nature of cells

(n + n = 2n)

↑ variation among offspring:

  • Random gametes fusing

  • Millions of possible chromosome combos in each gamete


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Summary of Meiosis

Nuclear division that halves chromosome number

Results in n male & female gametes that can fuse during fertilization to produce 2n offspring


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Chromosomal Abnormalities

Abnormal chromosome structure:

Breakage of chromosome leads to rearrangements that affect genes on that chromosome

Abnormal chromosome number:

Chance events occur before or after cell division that result in wrong chromosome #


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Changes in Chromosome Structure

Can have neutral to harmful effects, depending on type of chromosomal change

4 types of rearrangement:

  • Inversion

  • Deletion

  • Duplication

  • Translocation


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(a) Inversions

Broken fragment reattaches to original chromosome but in reverse direction

Genes still present in normal #, so less harmful than other categories


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(b) Deletions

Fragment of chromosome is lost

Cause severe physical & mental problems

e.g. cri du chat


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(c) Duplications

Fragment from one chromosome joins to a sister chromatid or homologous chromosome

Can have severe effects


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(d) Translocations

Fragment of chromosome attaches to non-homologous chromosome

May or may not be harmful


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If chromosomal changes occur in sperm or egg cells:

= may cause congenital disorders

If chromosomal changes occur in somatic cells:

= can lead to development of cancer

(which is why cancer is generally not heritable)


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Heritable Changes in Chromosome #

Chance events occur before or after cell division that result in wrong chromosome #

Consequences can be minor or lethal


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Most changes in chromosome number occur because of non-disjunction

= 1 pair of chromosomes do not separate during mitosis or meiosis


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Aneuploidy:

Normal #  1 chromosome

e.g. trisomy 21 (Down Syndrome)

Polyploidy:

3n, 4n, etc.

Normal in many plants & animals


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# of sex chromosomes can also be abnormal

E.g. XO, XXX, XXY, XYY

Will return to this when covering inheritance


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