Cell Division

• Cell division is important for cells to receive genetic material to function, to grow, to heal/repair, and to replace dead cells

  • Genetics - The study of heredity and variation of living organisms and how genetic information is passed from one generation to the next

• The cell theory, one of the central ideas in biology, states that:

  • All living things are composed of one or more cells

  • Cells are the smallest units of living organisms

  • New cells come only from pre-existing cells by cell division

    • This turns a parent cell into daughter cells

• All somatic cells go through cell cycles to become two cells

  • Somatic Cell - A plant or animal diploid cell that forms the body of the organism; excludes reproductive cells

The Cell Cycle

• The three main stages of the cell cycle are interphase, mitosis, and cytokinesis

  • Interphase is the majority of the cell cycle

• Interphase - The stage of the cell cycle during which a cell carries out its normal functions, grows, and makes copies of its genetic material in preparation for the next stage of the cycle

  • The cell grows, matures, copies its DNA, and prepares for division

  • Growth 1 is the major period of growth where the cell synthesizes many new molecules

  • Synthesis is the period where DNA is replicated as uncondensed fibres called chromatin

  • Growth 2 involves the production of more molecules

• Mitosis - The stage of the cell cycle where a cell’s nucleus and genetic material divide

  • Prophase - The stage where the cell’s chromatin condenses into chromosomes, the nucleus and nucleolus disappear, and spindle fibres form from the centrosomes and move towards the poles

    • Each chromosome exists as two copies of one chromosome called sister chromatids, as they have been replicated in interphase

      • Chromosome - A structure in the nucleus that contains DNA

      • Sister Chromatid - One of two chromosomes that are genetically identical and held together at the centromere

        • Centromere - The region where two sister chromatids are held together in a chromosome

    • Spindle Fibre - A microtubule structure that facilitates the movement of chromosomes within a cell

    • Centrosome - A structure that helps to form the spindle fibres

  • Metaphase - The stage where the spindle fibres from each pole attach to the centromere and guide the chromosome to the equator of the cell

  • Anaphase - The stage where each centromere splits apart, and sister chromatids, now individual chromosomes, are separated to opposite poles so that each pole has a complete set of DNA

  • Telophase - The stage that begins when chromosomes reach the opposite ends of the cell, where chromosomes start to unwind, spindle fibres break down, and the nucleus and nucleolus reform

• Cytokinesis - The stage of the cell cycle that involves the division of the cell cytoplasm and creation of two new daughter cells

  • In animal cells, an indentation forms and deepens as microfilaments constrict until the cell is pinched in two

  • In plant cells, a new cell plate forms between the two daughter nuclei, and cell walls form on either side of the plate

  • In prokaryotic cells, the duplicated DNA is pulled apart, and binary fission separates the cells

  • The daughter cells then begin interphase at G1

• Cell cycle checkpoints monitor cell growth

• Cell growth is monitored by a network of signals

The Structures of Genetic Material

• DNA is made of two long strands that form a spiral shape called a double helix

• DNA is usually in strands of chromatin, until mitosis begins

• The individual units of each strand of DNA are called nucleotides, made of a phosphate group, a sugar group, and a base

  • Sugar and phosphate groups serve as the backbones of the strands

  • The bases protrude inwards, and are paired as either adenine and thymine (A and T) or guanine and cytosine (G and C)

• Genome - The complete DNA sequence of an organism

• To replicate DNA, the double helix is unwound, and the bases on each strand of DNA serves as a template for a new strand, called semi-conservative replication because half of the original DNA is kept

Chromosomes

• Chromosomes are always paired

• In humans, one half comes from each parent, which are paired as homologous chromosomes

  • Sex Chromosome - An X or Y chromosome, which determines the genetic sex of an organism

    • Females have two X chromosomes, and males have an X and an Y

  • Autosome - A chromosome that is not involved in determining the sex of an organism

  • Homologous Chromosome - A chromosome that contains the same sequence of genes as another chromosome

    • They have similar length, centromere location, and banding patterns, but can have different forms genes

    • Gene - A functional part of a chromosome that contains information for inheritance, governs the expression of a trait and is passed on to offspring; it has a specific DNA sequence

    • Allele - A different form of the same gene

• Karyotype - A photograph of pairs of homologous chromosomes in a cell

  • A sample of chromosomes is stained, sorted, and paired

  • The autosomes are labeled as pairs 1 to 22, and the sex chromosomes are labeled as X or Y

  • To write a karyotype, use the following notation:

    • # of chromosomes, all sex chromosomes ± the autosomal chromosome that has aneuploidy

Sexual Reproduction

• Asexual Reproduction - Reproduction that requires only one parent and produces genetically identical offspring

• Sexual Reproduction - Reproduction that requires two parents and produces genetically distinct offspring

  • This involves the fusion of male reproductive cells with a female reproductive cell

  • Gamete - A male or female haploid reproductive cell

  • Zygote - A cell formed by the fusion of two gametes in fertilization

  • Fertilization - The joining of male and female haploid cells

  • Gametes have half the number of chromosomes than the parent somatic cell

    • Haploid - A cell that contains half the number of chromosomes as the parent cell, represented by n

    • Diploid - A cell that contains pairs of homologous chromosomes, represented by 2n

Meiosis

• Meiosis - The cellular process that produces cells containing half the number of chromosomes as the parent cell (genetic reduction) and are genetically unique through combinations of alleles (genetic recombination)

• Interphase Before Meiosis- Cells that will divide by meiosis will proceed through growth and synthesis, and replicate their chromosomes, so that the meiosis begins with duplicated chromosomes

• Meiosis has two complete cycles

• Prophase I - Each pair of homologous chromosomes condense and line up side by side in synapsis, where genetic information is exchanged through crossing over

  • Homologous chromosomes come together to form a tetrad

  • Tetrad - Two chromosomes or four chromatids

  • Chiasma - The site where chromosomes cross over

  • This is the longest meiotic phase

• Metaphase I - The pairs of homologous chromosomes (tetrads) line up along the equator of the cell, and spindle fibres attach to the centromere of each homologous chromosome

  • This is the shortest meiotic phase

• Anaphase I - The homologous chromosomes separate and move to opposite poles, which turns a diploid cell into a haploid cell

  • Sister chromatid remain attached

• Telophase I - Homologous chromosomes begin to uncoil and the spindle fibres disappear, the nuclear membrane forms, and two haploid cells form through cytokinesis

• Prophase II - The nuclear membrane disappears and spindle fibres reappear

• Metaphase II - A haploid number of chromosomes line up at the equator

• Anaphase II - Sister chromatids are pulled apart at the centromere by the spindle fibres towards opposite poles of the cells

• Telophase II - The nuclear membrane and nuclei reform

• Cytokinesis occurs, resulting in four unique haploid cells

• Spermatogenesis - The process of producing male gametes in mammals

  • It begins with a diploid cell called a spermatogonium, which reproduce beginning at puberty by mitosis, and then undergo meiosis

  • Following meiosis II, the cells undergo a final set of developmental stages to develop into four mature sperm

• Oogenesis - The process of producing female gametes in mammals

  • Meiosis takes place in the ovaries

  • It begins with a diploid called an oogonium, which reproduces before birth by mitosis

  • They begin meiosis, but stop at prophase I, where one cell will complete meiosis I every month after puberty

  • This involves an uneven division of cytoplasm, so that the meiosis will form one large, viable egg and a non-viable polar body

  • Once fertilized by sperm, the egg will finish meiosis II and produce one mature egg, and another polar body

  • Twins can be caused by two eggs that are both fertilized, or if a single zygote is divided into two separate bodies

• Meiosis forms genetically distinct haploids through independent assortment, random selection, and crossing over

  • Independent Assortment - The orientation of each chromosome in a homologous pair to one pole, which can result in a variation of possible gametes containing a combination of maternal and paternal chromosomes

    • For genes to be sorted independently, they must be on separate chromosomes

    • The number of genetically distinct gametes can be represented by 2ⁿ

    • Occurs during metaphase I

  • Crossing Over - The exchange of chromosomal segments between a pair of homologous chromosomes during prophase I

    • As a result, individual chromosomes contain some genes of maternal origin and some genes of paternal origin

• Errors during meiosis in both independent assortment and crossing over can result in abnormalities of chromosome structure

  • Deletion - A piece of a chromosome is deleted

  • Duplication - A section of a chromosome appears two or more times in a row

  • Inversion - A section of a chromosome is inverted

  • Translocation - A segment of one chromosome becomes attached to a different chromosome

• Errors in chromosome numbers are the result of non-disjunction

  • Non-disjunction - The failure of homologous chromosome pairs or sister chromatids to separate during the anaphase stages in meiosis

    • If it occurs during anaphase I, two gametes will have one extra, and two gametes will have one fewer

    • If it occurs during anaphase II, two gametes will have the normal amount, one gamete will have one extra, and one gamete will have one fewer

  • Monosomy - The loss of a chromosome in an autosome as a result of non-disjunction

  • Trisomy - The gain of an extra chromosome in an autosome as a result of non-disjunction

• Common chromosomal abnormalities in humans

  • Down Syndrome - Trisomy 21, and includes intellectual disabilities and a short stature

  • Edward’s Syndrome - Trisomy 18, and includes intellectual and physical disabilities and facial abnormalities

  • Patau’s Syndrome - Trisomy 13, and includes intellectual and physical disabilities, many organ defects, and a large triangular nose

  • Klinefelter’s Syndrome - XXY, and includes sexual immaturity

  • Jacobs’ Syndrome - XYY, and may be taller than average

  • Metafemale - XXX, and includes menstrual irregularity

  • Turner’s Syndrome - XO, and includes a short stature and underdevelopment sexually

• Prenatal genetic testing involves tests performed on a fetus to test for genetic-based abnormalities

  • This can include maternal blood tests and ultrasounds to provide information about potential physical and chromosomal abnormalities, which are non-invasive

    • Fetal proteins and fetal neck fluids are obtained and tested

  • Invasive procedures include collecting fetal DNA through amniocentesis, the taking a sample of amniotic fluid in the 14th week, or chorionic villus sampling, where cells from the chorion of the placenta are sampled in the 9th week of pregnancy

Cancer

• Hayflick Limit - The limit of the life span and amount of division of different types of body cells

• The cell cycle has checkpoints that determine whether the cell division should continue or not, and prevent the cell from undergoing mitosis uncontrollably

  • Proteins signal a stop in mitosis is something is wrong

  • G1 Checkpoint - Checks for DNA damage, cell size, nutrients and proteins for growth

  • G2 Checkpoint - Checks for successful DNA replication

  • Metaphase Checkpoint - Checks that chromosomes are correctly attached to spindles

• If the cell does not pass the checkpoints, the cell stops dividing and enters apoptosis

  • Apoptosis - Programmed cell death, where suicide genes produce proteins that kill the cell

  • Necrosis - Cells die from damage through toxic chemicals or physical forces

• Cancer - Cells divide uncontrollably as a result of DNA mutation and damage, where the genes that control checkpoints stop working

  • Cancer cells do not carry out their normal function

  • Tumor - A mass of cells that keeps growing and dividing without any obvious function

    • Benign Tumor - A tumor that physically crowds surrounding tissue, but does not affect it

    • Malignant Tumor - A tumor that interferes with the functioning of surrounding cells and outcompetes them

    • Metastatic Tumor - When cancer cells break off from a tumor and travel through blood and lymph to form a secondary tumor somewhere else in the body

  • Mutation - A random change in the DNA code

    • Can be caused by random mistakes, carcinogens, or inheritance

  • Ex. If the gene p53 is damaged, cells will continue dividing

Mendel’s Experiments

• Mendel used pea plants, which showed many traits

  • Trait - A specific characteristic or feature exhibited by an organism

• Pea-plants self-fertilize, which gave their offspring predictable traits

  • True Breeding - Organisms that exhibit the same traits, generation after generation

• Mendel crossed specific female and male gametes in his experiment

  • Cross - The fertilization of a female gamete of specific genetic origin with a male gamete of a specific genetic origin

• Mendel observed seven traits: stem length, pod shape, pod colour, seed colour, seed shape, flower position, and flower colour

• Mendel would begin his experiments with parental, true-breeding plants

  • P Generation - In breeding, the organisms initially crossed and are typically true breeding

  • He would breed parents with different traits to produce offspring

    • F₁ Generation - The offspring of a cross of the P generation

    • F₂ Generation - The offspring of a cross between the F₁ generation

    • He found that in seed colour, all of the F₁ generation was yellow (dominant colour), but the F₂ generation expressed both phenotypes

      • Mendelian Ratio - An approximate ratio of 3:1 for dominant to recessive phenotypes in a monohybrid cross between two heterozygous parents

        • The larger the sample group, the closer to this ratio the result will be

  • Monohybrid Cross - A cross of two individuals that differ by one trait

• Theory of Particulate Inheritance - Recessive genes can be discretely inherited through generations, which causes traits to go unexpressed in the F₁ generation, but reappear in the F₂ generation

• Law of Segregation - Traits are determined by pairs of alleles that segregate during meiosis so that each gamete receives one allele

• Law of Independent Assortment - During gamete formation, the two alleles for one gene segregate or assort independently of the alleles for other genes on other chromosomes

• Dominant - The form of a trait that always appears when an individual has an allele for it

  • Usually represented by capital letters

• Recessive - The form of a trait that only appears when an individual has two alleles for it

  • Usually represented by lowercase letters

• Genotype - The combination of alleles for any given trait, or the organism’s entire genetic make-up

  • Heterozygous - An organism that has two different alleles of a gene

  • Homozygous - An organism that has two identical alleles of a gene

    • Can be homozygous dominant or homozygous recessive

• Phenotype - The physical and physiological traits of an organism

Monohybrid Crosses

• These use a cross of only one trait

• A cross between two heterozygous parents should express a ratio of 3:1 of dominant to recessive phenotypes

• Follow these steps:

  • Write a legend

  • Write and box the parent line

    • If part of the genotype is unknown, leave blanks where the alleles should go

  • Illustrate, with arrows, the possible gametes produced by each parent

  • Perform the cross with a 2×2 Punnett square and/or a pedigree

    • For a Punnett Square, male gametes go on top, each column/row has its own gamete, the grid between should express the possible combinations from both parents

    • For a pedigree:

      • Males are squares, females are circles

      • Generations are labeled with Roman numerals, and individuals are numbered

      • Carriers have a black dot, and affected individuals are completely shaded in

      • Twins branch from the same spot

  • Express the genotypes and/or phenotypes through ratios

• When given the offspring, but not the full parent line, decide which genes certainly had to come from each parent by considering homozygous genotypes and past crosses

• Test Cross - A cross between a parent of an unknown genotype and a homozygous recessive parent

  • If the offspring only express the dominant trait, the unknown is homozygous dominant

  • If the offspring express either trait, the unknown is heterozygous

Dihybrid Crosses

• Dihybrid Cross - A cross of two individuals that differ in two traits due to two different genes

• A cross between two fully heterozygous parents should express a ratio of 9:3:3:1 of dominant/dominant to dominant/recessive to recessive/dominant to recessive/recessive phenotypes

• Follow the same steps as a monohybrid cross, except with a 4×4 Punnett Square

  • Each parent should produce four gametes

    • Typically the number of gametes is solved by 2ⁿ, where n is the number of traits

    • For linked genes, the number of traits is the number of independently assorted traits

      • These genes are inherited together, but can be broken during crossing over

      • The genotype should be written with the linked genes together, with a line over them

        • Ex. If A and B, and a and b are linked, write ABab with a bar over it, instead of AaBb

  • If a parent produces identical gametes, then the Punnett square can be reduced to only crossing each identical gamete once

Polygenic Traits

• Continuous Variation - Multiple allele pairs spread throughout the chromosomes

• Polygenic Traits - Traits controlled by multiple alleles

Codominant Genes

• Codominant Gene - Two different alleles at a locus are responsible for different phenotypes, and both alleles affect the phenotype of the heterozygote

Blood Types

• Blood types depend on the antigens (agglutinogens) present on the surface of an individual’s red blood cells

  • Agglutinogens A - Type A

  • Agglutinogens B - Type B

  • Agglutinogens A and B - Type AB

  • No Agglutinogens - Type O

• Antibodies (agglutinins) present in the blood can attack specific antigens, causing agglutination (clumping) and hemolysis, and thus limit compatibility

  • Type A - Anti-B Agglutinins

  • Type B - Anti-A Agglutinins

  • Type AB - No Agglutinins

  • Type O - Anti-A and Anti-B Agglutinins

• I^A and I^B are codominant over i

  • Type A - I^AI^A or I^Ai

  • Type B - I^BI^B or I^Bi

  • Type AB - I^AI^B

  • Type O - ii

• The Rh factor is another type of antigen

  • Rh+ - RR or Rr

  • Rh- - rr

  • Anti-Rh antibodies are not present in Rh- blood unless the blood is sensitized to Rh+ blood first

• Rh Hemolytic Disease

  • An Rh- mother carries an Rh+ baby, and becomes sensitizes to the Rh+ (she produces antibodies)

  • If the mother carries a second child with Rh+, the antibodies will attack the baby

• Compatibility

  • Blood types cannot receive blood with antigens that it has antibodies against

    • Ex. Type A cannot receive type B because it has anti-B antibodies, but type AB can receive type B because it has no antibodies

  • Rh- can only receive Rh-, but Rh+ can receive Rh+ or Rh-

Incomplete Dominance

• Incomplete Dominance - The phenotype of a heterozygote is a blend of both the dominant and recessive traits

Sex-Linked Genes

• Sex Linked Gene - A gene coded on a sex chromosome

• Sex linked recessive traits

  • If it is linked to the X, males can never be carriers, as the presence of just one allele makes its single X affected

  • XX - Normal female

  • X^aX - Carrier female

  • X^aX^a - Affected female

  • XY - Normal male

  • X^aY - Affected male

• Sex linked dominant trait

  • Anyone with an affected allele is affected

  • XX - Normal female

  • X^AX or X^AX^A - Affected female

  • XY - Normal male

  • X^AY - Affected male

• Hemizygous - If there is only one copy of a gene for a particular trait, such as X-linked genes in males

Lethal Alleles

• Lethal Allele - A mutated gene that is capable of causing death

  • Dominant lethal alleles typically kill both heterozygotes and dominant homozygotes

  • Some lethal alleles kill when there is a lethal homozygous genotype, but show abnormal phenotypes in heterozygotes

    • The ratio for a cross between two abnormal phenotypes are usually 1:2:1, dead (lethal homozygote) to heterozygote to normal homozygote

• Wild-Type Allele - The non-mutant form of a gene, encoding the normal genetic function

Complementary Genes

• Complementary Genes - Genes can only be expressed in the presence of other genes

• A_bb would be the recessive phenotype, aaB_ would be the recessive phenotype, and A_B_ would be the dominant phenotype

• The ratio for a cross of two completely heterozygous parents is 9:7 for dominant to recessive

Epistasis

• Epistasis - One gene masks the expression of a different gene for a different trait

• If the genotype bb masks a gene, A_bb would not show a trait, aaB_ would show the recessive phenotype for gene A, and A_B_ would show the dominant phenotype for A