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Genetics Study Notes - Summary - lectures 1 - 6, 9 - 13

Genetics (Western Sydney University)

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Week 1
Epigenesis –an organism arises from an egg that differentiates into adult structures

Genetics is the study of inherited traits; inherited traits are determined by the elements of heredity – genes (DNA)

Genes are segments of the DNA molecule

1866 Mendel discovered ‘factors’, 1869 Friedrich Miescher discovered DNA

Two types of nitrogen-containing bases comprise the chemical structure of DNA:

 Purines = adenine and guanine

 Pyrimidine’s = thymine and cytosine

Pairing between nucleotides of double helix is complementary: adenine pairs with thymine, guanine pairs with cytosine

Enzymes = proteins encoded by genes which are biological catalysts essential for metabolic activities in the cell

Polypeptide = a chain of linked amino acids

DNA codes for RNA = transcription RNA codes for protein = translation

Transcription is the production of an RNA strand that is complementary in base sequence to a DNA strand = mRNA

Bases in DNA: Adenine, thymine, guanine, and cysteine RNA: Uracil, adenine, cysteine, and guanine

DNA vs. RNA =

DNA sugar deoxyribose, RNA sugar ribose
DNA double stranded, RNA single stranded

 Translation
MRNA contains genetic code in triplet base codons that specify the sequence of amino acids in proteins
Transfer RNAs (tRNA) contain triplet base sequences = are complementary to codon sequences in mRNA and
position amino acids during translation

In the triplet code, three consecutive bases specify an amino acid, creating 43 (64 possible code words.

Mutation refers to any (heritable!) change in a gene

Base substitutions can alter the genetic code which specifies amino acid placement in proteins
Mutations produce alleles of a gene, and they are the source of genetic variation

Plieotrophy: The phenomenon of a single gene responsible for unrelated phenotypic effects

DNA cloning steps:

1. Vector and DNA fragment are joined to produce a DNA molecule
2. DNA is inserted into cell
3. DNA is cloned into many copies by replication & division

Genome / Proteome

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Genome = the totality of the DNA in a cell or in sexually reproducing organisms the DNA present in a reproductive cell

Proteome = Complete set of proteins coded for by a genome

Week 2

Mitochondria are the sites of cellular respiration, generating ATP from the catabolism of sugars, fats, and other fuels in
the presence of oxygen.

Chloroplasts: found in plants and eukaryotic algae, are the site of photosynthesis

Mitochondria and chloroplast have their own DNA - they can duplicate, transcribe & translate their genetic information

In the nucleus is a region of densely stained fibers and granules adjoining chromatin, the nucleolus
In the nucleolus, ribosomal RNA (rRNA) is synthesized and assembled with proteins from the cytoplasm to form
ribosomal subunits

Ribosomes contain rRNA and protein:

- A ribosome is composed of two subunits that combine to carry out protein synthesis.
- Cell types that synthesize large quantities of proteins (e.g., pancreas) have large numbers of ribosomes

Human Chromosome
human body or somatic cells have 46 chromosomes organized as 23 pairs which are homologous (homologs) because
each pair contains the same genes (may have different alleles)

• Humans are thus diploid (2n) = 2 copies of each chromosome, except for the sex chromosomes (X+Y) which are non-
identical

• Gametes (germ cells) are haploid (n) (1 of each chrom.)

Mitosis
is responsible for growth and repair
- tree height & root growth
- Hair, bone, skin growth and repair

• enables asexual reproduction

Cell cycle G1-S-G2-M

Cells spend most time (90%) in interphase

- Cells grow
- perform their functions
- DNA replicates
- organelles are also duplicated in preparation for cell division
G1 = gap 1; G2 = gap 2 ; S = synthesis, M = mitosis

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Cell cycle
Cell division cycles occur in stages:

- G1 = pre-DNA synthesis

- S = DNA synthesis

- G2 = post-DNA synthesis

- M = mitosis: cell division occurs by precise steps which distribute one set of chromosomes to each of two cells

Necrosis = localised tissue death (swelling and rupture of injured cells)

Apoptosis = also called programmed cell death is a specific process of dismantling and saving a cells components

Macrophages (big eaters) are often responsible for phagocytosis

• Interphase -

– Chromosomes are not visible - diffuse granular appearance

– nucleoli may be visible (ribosomal RNA + ribos. synth.)

• During S - DNA replication: exact duplicates = sister

Chromatids attached at the centromere

• In G2 the centrosome (region of cytoplasm containing

Centriole -microtubule organizing center) divides

• A centrosome duplication checkpoint (G2/M) delays

Entry into M until centrosome duplication is complete

Stages of Mitosis

Prophase-

• Centrioles migrate to poles (they organize cytoplasmic microtubules into spindle fibers), however, centrioles Not
universally responsible for formation of spindle fibers

• Chromosomes are visible, and continue to condense becoming shorter & thicker

• The nucleoli disappears and the nuclear membrane disintegrates

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Metaphase-

Prometaphase (the movement of chrom. to the metaphase plate)

• A bipolar mitotic spindle (microtubules) forms between the centrosomes

• Spindle fibers attach to the kinetochore (in the region of the centromere), chromosomes line up in center of cell =
metaphase plate

Anaphase

Centromeres divide longitudinally

Sister chromatids separate: one member of each pair is pulled to either pole of the cell as spindle fibers shorten, each
chromatid now a single chromosome

• Both groups of chrom. now the same as in the original nuclei

Telophase –

Spindle disappears

• Nuclear membranes + nucleoli form

• Chromosomes un-condense

• Cytoplasm divides, the two cells are diploid = each contains both members of every pair of chromosomes

• Cytokinesis = cytoplasmic division

Cytokinesis - in plants a cell plate forms and in animals the cell constricts producing a cell furrow

MEIOSIS

Two rounds of cell division result in the formation of gametes which are genetically haploid = contain only one copy

of each pair of homologous chromosomes

Meiosis is a specialized type of cell division which occurs only in reproductive cells = germ cells

meiosis I

• Each daughter cell contains only one member of each homologous pair of chromosomes

meiosis II

• cell division occurs in the absence of chromosome duplication

- sister chromatids separate at anaphase (as in mitotic division)

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Meiotic vs. Mitotic Division

• Mitosis produces two cells which contain both members of each pair of homologous chromosomes = genetically
diploid

• Meiosis produces four cells, each of which contains one copy of each pair of homologous chromosomes = genetically
haploid

Mitosis and meiosis

• Mitosis makes exact copies, maintains exact numbers of chromosomes, diploid to diploid – has to do with growth and
repair

• Meiosis makes exact copies then mixes alleles, and reduces the chromosomes number to form gametes – diploid to
haploid

• Meiosis I & II - REDUCTION & DIVISION

– Reduction of chromosome # & division of chromatids

– has to do with sexual reproduction

Meiosis I: Stages

Prophase I - a unique process of genetic recombination occurs

- Homologous chromosomes pair = synapsis

- Physical exchange of genetic material occurs between homologous chromosomes

- Chiasmata = linkage points

Prophase I: 5 Sub stages

• Leptotene - ‘thin thread’ chromosome condense become visible, chromomeres appear on the threads

– Under electron mic. Sister chromatids are visible

• Zygotene - ‘paired thread’ pairing or synapsis of homologous chromosomes

– A pair of synapsed homologous chromosomes = bivalent,

– Chromatids are not visible at this stage

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• Pachytene - ‘thick thread’ condensation of chrom. Continues

• Crossing-over between homologous chromosomes occurs, tetrad may be visible.

– ie bivalent appears as tetrad because chromatids become visible

Diplotene - ‘double thread’ synapsed chromosomes begin to separate but held together at chiasma (plural chiasmata)

• Diakinesis- “moving apart’ maximum chromosome contraction or condensation prior to metaphase I

Independent Assortment

• Random alignment of homologous chromosomes during metaphase I results in independent assortment of non-
homologous chromosomes

• This occurs because the genetic elements on non-homologous chromosomes are unlinked = inherited as separate
physical units

Meiosis I

• Metaphase I - homologous chromosomes line up at metaphase plate; random alignment of nonhomologous

chromosomes is the basis of the Law of Independent Assortment

• Anaphase I -the physical separation of homologous chromosomes to the opposite poles of spindle-demonstrates Law
of Segregation;

Meiosis I and II

• Telophase I - spindle breaks down, nuclear reorganization occurs; one homolog from each bivalent is at each pole

• Second Meiotic Division occurs in absence of chromosome replication

• Meiosis II = equational division as the number of chromosomes in each cell remains constant

Meiosis II

• Meiosis II consists of prophase II, metaphase II, anaphase II and telophase II which are ‘identical’

to the stages of mitosis

• Anaphase II - centromeres divide & sister chromatids of each chromosome separate

• Telophase II - each cell contains haploid chromosome number, one member of each homologous pair

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Chromosome Structure

• Eukaryotic chromosomes are highly coiled complexes of a single DNA mol. and protein

• Chromosome size is measured in kb= kilobase pairs; 1 kb=1,000 base pairs; 1 Mb (megabase) = 1 million base pairs

• Chromosome-sized DNA molecules can be separated by electrophoresis in which DNA molecules move in response to
electric field

Chromatin Structure

• Chromatin is a stable, ordered complex of DNA and protein

• Histones = major class of basic (small) proteins in chromatin fibers

• Five major types of histones are found in chromatin: H1, H2A, H2B, H3 and H4 - histones are responsible for the
structure of chromatin

Chromatin Structure

• Nucleosome = the bead like units in chromatin (as viewed under electron mic.

• Each nucleosome core contains about 200 bps of DNA wrapped around a core of histone proteins

• Linker regions of DNA occur between adjacent nucleosomes

• Structure termed: beads on a string

Chromatin Structure

Nucleosomes coil to for higher order DNA structure = 30 nm fiber which is a left-handed superhelix or solenoidal
supercoil; contains 6 nucleosomes per turn

Chromatin Structure

• Heterochromatin = compact, heavily staining chromosome regions rich in satellite DNA and low in gene content

• Euchromatin= less condensed chromosome regions high in gene content

• Satellite DNA = highly repeated non-coding DNA sequences

Teleomeres are special DNA-protein structure found at the ends of chromosomes essential for chromosome stability

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Sex Chromosomes

• X and Y chromosomes = sex chromosomes which are non-identical but share some genes

• Males are genetically haploid for most genes on the X chromosome which results in unique pattern of X-linked
inheritance

• Autosomes = non-sex chromosomes

X-Linked Inheritance

• Genes on the X-chromosome are X-linked

• Females = XX; Males = XY

• Sex of progeny is determined by X or Y of sperm

• Morgan discovered X-linked inheritance by identifying mutations exclusive to male fruit flies

Spermatogenesis takes place in the testis and the stem cells that give rise to sperm, spermatogonia are located in
seminiferous tubule

• The developing sperm cell move towards the central opening (lumen) of the tubule as they undergo meiosis and
differentiation.

• All four cells that result from meiosis develop into mature sperm cells

Oogenesis is the development of ova, - mature, unfertilized egg cells

• In the developing female embryo oogonia the stem cells that give rise to ova multiple and then begin meiosis, but
stops at prophase I (primary oocytes), remain quiescent within small follicles until puberty

At puberty FSH periodically stimulates a follicle to grow and induces it primary oocyte to complete meiosis I and start

meiosis II.

• Meiosis STOPS again, the secondary oocyte released at ovulation does not continue meiosis II right away

• In humans penetration of the egg cell by the sperm triggers the completion of meiosis and only then is oogenesis
complete

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Week 3 Gregory Mendell

– Character: a heritable feature, such as flower color, pea shape

– Trait: a variant of a character, such as purple or white flowers, smooth or wrinkled peas

Mendel mated two contrasting, true-breeding varieties, a process called hybridization

• The true-breeding parents – are called the P generation

The hybrid offspring of the P generation

– Are called the F1 generation

• When F1 individuals self-pollinate

– The F2 generation is produced

Law of Segregation

A ratio of about three to one, purple to white flowers, in the F2 generation

Purple flower color was dominant, and white flower color was recessive
Mendell made a hypothesis, 4 concepts:

 Alternative versions of genes account for variations in inherited characters, which we now called alleles (alleles
are alternative forms of a gene)
 Second, for each character
– An organism inherits two alleles, one from each parent
– A genetic locus is actually represented twice

 Third, if the two alleles at a locus differ

– Then one, the dominant allele, determines the organism’s appearance
– The other allele, the recessive allele, has no noticeable effect on the organism’s appearance

 Fourth, the law of segregation

– The two alleles for a heritable character separate (segregate) during gamete formation and end up in different
gametes

Law of Independent Assortment

Mendel identified his second law of inheritance – The Law of Independent Assortment – By following two characters at
the same time

Crossing two, true-breeding parents differing in two characters

– Produces dihybrids in the F1 generation, heterozygous for both characters

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A dihybrid cross

– Illustrates the inheritance of two characters

• Produces four phenotypes in the F2 generation in a ratio of 9:3:3:1

The number of combinations possible when chromosomes assort independently into gametes is 2n, where n is the
haploid number of the organism.

– If n = 3, there are eight possible combinations.

The random nature of fertilization adds to the genetic variation arising from meiosis.

The laws of probability govern Mendelian inheritance

Mendel’s laws of segregation and independent assortment

– Reflect the rules of probability

• The Multiplication and Addition Rules can be applied to Monohybrid and other Crosses

Probability (P or p)

= the number of times a specific event can happen

The total number of possible events

• Multiplication Rule: The probability of two independent events occurring simultaneously equals the product of their
individual probabilities

– P (tossing 2 heads in a row) =1/2 x 1/2 = 1/4

• Addition Rule: The probability of obtaining one or the other of two mutually exclusive events is the sum of their
individual probabilities

– P (tossing a head or a tail) = 1/2 + 1/2 = 1

Complete dominance

– Occurs when the phenotypes of the heterozygote and dominant homozygote are identical

• E.g. PP appears the same as Pp that is they have the same phenotype

Codominance

Two dominant alleles affect the phenotype in separate, distinguishable ways e.g. human blood

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Dominant and recessive alleles

– Do not really “interact”

– Lead to synthesis of different proteins that produce a phenotype

Dominant alleles

– Are not necessarily more common in populations than recessive alleles

An organism’s phenotype

– Includes its physical appearance, internal anatomy, physiology, and behavior

– Reflects its overall genotype and unique environmental history

Pedigree: A family tree that describes the interrelationships of parents and children across generations

• Pedigrees

– Can also be used to make predictions about future offspring

• Many genetic disorders

– Are inherited in a recessive manner

• Recessively inherited disorders

– Show up only in individuals homozygous for the allele

• Carriers

– Are heterozygous individuals who carry the recessive allele but are phenotypically normal

• Wild type = the most common form of a trait occurring in a population

• Mutant = any form that differs from the wildtype

• Electrophoresis is a general term for any technique that separates and/or characterises charged particles based on
their specific migration rates in an electric field

Visible trait = one that is readily perceived

Molecular trait = perceived only by special methods

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Week 4:

Fruit flies were excellent tools for research due to short generation time, large number of offspring, and ease of
producing and analyzing mutations

Codominance is characterized by distinct expression of the gene products of both alleles e.g. MN antigens on blood cells

Incomplete dominance the heterozygote expresses an intermediate, ‘blended’ phenotype e.g. pink flower

Antibodies are specific proteins which bind to stimulating molecules or antigens

Nondisjunction = chromosomes fail to separate properly during anaphase of meiosis I or II

• This results in unbalanced chromosome segregation, such that one cell receives both copies of the chromosome pair

• Nondisjunction in meiosis I produces gametes with a pair of homologous chromosomes

• Nondisjunction in meiosis II produces gametes with a pair of sister chromatids

Nondisjunction can occur for any human chromosome resulting in zygotes with an abnormal number of chromosomes =
aneuploidy

• Trisomy of chromosome 21 is the most common autosomal aneuploidy = Down’s syndrome

Plieotrophy

The phenomenon of a single gene being responsible for number of distinct and seemingly unrelated phenotypic effects

• e.g. a pleiotropic effect white haired blue eyed cats - 40% are born deaf - reason unknown

Sickle cell disease caused by the substitution of a single amino acid in hemoglobin

Codominance modifies the 3:1 ratio in a monohybrid cross (instead we got 1:2:1).

Epistasis

Is a type of gene interaction

– Specifically it may be defined as the non-reciprocal interaction of non-allelic genes

– that is alleles of one gene may interfere with those of another gene but not vice versa

there are 9 (or more) possible modified ratios with 9:7; 12:3:1; 13:3, 9:4:3 and

9:6:1 the more common

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In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus.

– e.g., in mice and many other mammals, coat color depends on two genes.

– One, the epistatic gene, determines whether pigment will be deposited in hair or not.

• Presence (C) is dominant to absence (c).

– The second determines whether the pigment to be deposited is black (B) or brown (b).

• The black allele is dominant to the brown allele.

– An individual that is cc has a white (albino) coat regardless of the genotype of the second gene.

Epistasis

• 9:3:4 ratios is observed when homozygosity for a recessive allele masks the expression of the genotype of a different
gene (mouse/dog example)

• 9:7 ratios occurs when a homozygous recessive mutation in either or both of two different genes produces the same
phenotype

Epistasis

• 12:3:1 ratio results when a dominant allele of one gene masks the genotype of a different gene (see the example of
fruit colour in summer squash in text)

• 9:6:1 ratio occurs when homozygosity for a recessive allele of either of two genes results in the same phenotype but
the phenotype of the double homozygote differs (see novel genotypes in summer squash in text)

Complementation analysis can determine if two mutations causing a similar phenotype are alleles

Expressivity & penetrance

The level (or range) of expression of a particular genotype is expressivity, e.g. if R is a dominant gene for red flowers R_
individuals will have red flowers but individuals may vary in the intensity of red.

The level of penetrance is the proportion (or percentage) of individuals of a given genotype who express a given
phenotype, e.g. if R_ = red flowers, penetrance is 100%.

Variable penetrance = the proportion of individuals that express

Variable expressivity = level of expression

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Week 5

Population genetics involves the application of genetic principles to entire populations of organisms

Application of genetic principals such as:

Segregation,
Independent assortment,
Recombination
Mutation, to entire populations

• Population = group of organisms of the same species living in the same geographical area

• Subpopulation = small population unit

• Local population = the predominantly interbreeding population

• Metapopulation = population made up of several discrete smaller populations

• Gene pool = all alleles in population

Genotype frequency = proportion of individuals in a population with a specific genotype

Allele frequency = proportion of alleles in a population

• Hardy Weinberg (HW) Principle analyzes the factors which may affect the frequencies of alleles in a population

• HW principle uses a simple equation to calculate allelic frequencies:

P = frequency (f) of all alleles = 1 (always total 1)

p = (f) dominant allele

q = (f) recessive allele p + q =1

Hardy Wein-berg conditions

• Mating is random (no subpopulations)

• Allelic frequencies are the same in males and females

• All genotypes have equivalent viability and fertility

• Mutation does not occur

• Migration into & out of the population is absent

• Population is large so that allelic variations do not occur by chance

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Random mating

Organisms form mating pairs that are independent of genotype

• Random mating is the most prevalent

• Self-fertilization = inbreeding, also refers to mating’s between relatives

p2 = pp = frequency of homozygous dominant genotype

2pq = frequency of heterozygous genotype

q2 = frequency of recessive genotype

When an ‘allele’ is rare there are many more heterozygotes than there are homozygotes if q = 0.1 then (1- q = p = 0.9)

• The ratio of heterozygotes to homozygotes is

2pq/q2 = 2(0.9)(0.1)/(0.1)2 = 18 or app 20

Hardy-Weinberg frequencies can be extended to multiple alleles:

-- Frequency of any homozygote = square of allele frequency

-- Frequency of any heterozygote = 2 X product of allele frequencies

Polymorphism: The presence in a population of two or more relatively common forms of a gene, chromosome, or
genetically determined trait.

Genetic Inbreeding

• Inbreeding means mating between relatives

• Inbreeding results in an excess of homozygotes compared with random mating

If random genetic drift were the only force at work all alleles would become fixed or lost and their would be no
polymorphism.

• Other facts however prevent the effects of drift

– Large pop size

– Mutation and migration (alleles lost can be reintroduced)

– Natural selection (particular selection that maintains genetic diversity such as heterozygote superiority)

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Which of the following genotype freq. (AA aa) satisfy the H-W principal?

a) 0.25AA, 0.50 Aa, 0.25 aa total = 1

a) p2 = .25 so p = 0.5 and q = 1-p = 0.5

p2 + 2pq + q2 = 1

= 0.25AA, 0.50 Aa, 0.25 aa

b) 0.64AA, 0.27 Aa, 0.09 aa total = 1

p2 = .64 so p = 0.8 and q = 1-p = 0.2

= 0.64 AA, 0.32 Aa, 0.04 aa

c) 0.49AA, 0.42 Aa, 0.09 aa total = 1

c) p2 = .49 so p = 0.7 and q = 1-p = 0.3

= 0.49 AA, 0.42 Aa, 0.09 aa

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Week 6

If a population consisted of half sexual females and half asexual females, the asexual condition would increase

These differences, termed sexual dimorphism, may include size differences, coloration differences, enlarged or
exaggerated features, or other adornments.

Primary sexual differentiation = involves only gonads (as opposed to secondary sexual characteristics)

Unisexual, dioecious and gonochoric all refer to an individual containing only male or female organs

Bisexual, monoecious and hermaphroditic refer to individuals containing male and female organs

The term intersex usually refers to individuals that are of intermediate sexual condition – often sterile

Sex determination must occur differently in different tissues of the same plant

•heterogametic sex has different sex chromosomes e.g. XY human males

•homogametic sex has homologous chromosomes e.g. XX human females

Klinefelter (47,XXY) and Turner (45,X)

Y determines maleness in HUMANS

X and Y pair during meiosis and there is a small region of homology between the two critical to segregation

• Y chromosome has at least 75 genes

• The pseudoautosomal regions (PARs) present on both ends of the Y chromosome that share homology with regions
on the X chromosome and synapse and recombine with it during meiosis

The non-recombining region of the Y chromosome is called the male specific region of the Y (MSY)

• It has euchromatic and heterochromatic regions

• The SRY (sex determining region) is located adjacent to PAR of the short arm of the Y chromosome

The testis-determining factor (TDF) is a protein encoded by a gene in the SRY that triggers testes formation

The MSY can be divided into three regions:

– X-transposed region (15 percent)

– X-degenerative region (20 percent)

– ampliconic region (30 percent, encodes

Proteins specific to the development and function of the testis

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AIS -androgen insensitivity syndrome

• A mutation on the X chromosome results in testicular feminisation where XY individuals are phenotypically female but
are sterile.

• The mutation prevents a response to the presence of testosterone and thus they do not develop secondary male
characteristics

Primary sex ratio reflects the proportion of males to females conceived in a population (hard to estimate)

Secondary sex ratio reflects the proportion of each sex that is born (easier to estimate)

• Females =2 copies of X chromosome

• One copy of X is randomly inactivated in all somatic cells = dosage compensation

• Females are genetic mosaics for genes on the X chromosome; only one X allele is active in each cell

• Barr body = inactive X chromosome

Mary Lyon, a British geneticist, demonstrated that the selection of which X chromosome to form the Barr body occurs
randomly and independently in embryonic cells at the time of X inactivation

• The mechanism of dosage compensation by X inactivation is called the single-active-X principle

X inactivation results from chromosome condensation, initiated at a site called XIC (X inactivation centre)

Sexual Mosaics = people whose bodies are a mixture of male and female tissues

Sex determination in Drosophila (revision)

• Drosophila is unusual in XY sex determining organisms

– the Y in flies is not sex determining

• XXY = normal fertile female (male in humans)

• XO = normal looking but sterile males

– Y is associated with maleness BUT not male determining

– XO males shows Y is not necessary for development BUT is for fertility

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Sex-limited traits = those traits expressed differently in the 2 sexes but are not sex linked

e.g. milk yield in cattle, egg laying in chickens

Sex-influenced traits = genotypes determined by autosomal genes are expressed differently in the two sexes

Sex chromosomes determine sex in some plants and animals (most mammals)

• But there is no universal mode of sex determination

Lecture 7

Chromosome mutations/abbreviations:

– Change in the total number of chromosomes

– Deletion or duplication of genes or segments of a chromosome

– Rearrangements of the genetic material either within or among chromosomes

Chromosome maps are prepared by dividing the chromosome into two regions (arms) separated by the centromere

Centromeres may be located in different regions of a chromosome:

• Metacentric = located in middle of chromosome

• Sub metacentric = located closer to one end of chromosome

• Acrocentric = located near the end of chromosome

Chromosomes lacking centromere = Acentric

Chromosome with 2 centromeres = Dicentric

1. euploid = balanced chromosome sets or equal number of copies of each chromosome or multiples of n e.g. 2n = 46 in
humans

2. aneuploid = unbalanced set of chromosomes or unequal copy number e.g. 3 of chromosome # 22 but 2 of all others,
or 1 of chromosome # 22 but 2 of all others e.g. 2n +1 = 47 or 2n-1 = 45 in humans

• acentric chromosomes are genetically unstable because they cannot be maneuvered

• dicentric chromosomes are genetically unstable because they cannot be transmitted in a predictable fashion

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Euploidy – balanced sets or multiples of n

• Diploidy (diploid) = 2n, e.g. 2n =46, humans

• Triploidy (triploid) = 3n, e.g. 3n = 69 humans

• Tetraploidy = 4n, e.g. 4n = 92 in humans

• Pentaploidy = 5n etc….

• Polyploidy = more than two sets e.g. 3n, 4n, 5n etc…

Polyploidy = genome composed of multiple complete sets of chromosomes; occurs mostly in plants.

Haploid = set of unpaired chromosomes found in gametes.

Monoploid = basic number of chromosmes in a polyploid series

 Monoploid = basic number in a polyploid series (a single set of chromosomes) - designated as X

 Haploid = number of chromosomes in gametes (n) and may be the same as the Monoploid number

Formation of polyploids in plants

• endoreduplication = doubling of the chromosome complement without cell divison

• autopolyploidy = chromosomes derived from single diploid

• allopolyploidy = chromosomes derived from two ancestral species, sometimes several hybridisation events are
involved

Endopolyploidy is the condition in which only certain cells in an otherwise diploid organism are polyploid

• In these cells, replication and segregation of chromosomes occur without nuclear division

Trisomy (2n + 1) down syndrome = 21

 Tolerated better by plants than by animals (interferes with chromosomal sex determination)

Trisomy 16

 chromosomal abnormality, but fetuses NEVER survive past the first trimester.
Note in this case that a sex chromosome is missing as well.

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Extra or Missing Chromosomes

• Polysomy = extra copies of single chromosomes in a cell

• Trisomy = extra copy of a chromosome

• Trivalent = abnormal pairing of trisomic chromosomes in cell division

• Univalent = extra chromosome in trisomy is unpaired in cell division

• Trisomy-X = 47, XXX (female)

• Double-Y = 47, XYY (male)

• Klinefelter Syndrome = 47, XXY (male, sterile)

• Turner Syndrome = 45, X (female, sterile)

• Fragile-X syndrome = X chromosome instability resulting from high copy number of trinucleotide repeat

Deletions = missing chromosome segment

Gene Duplications

• Duplication = chromosome segment is present in multiple copies

• Tandem duplications = repeated segments are adjacent

Chromosome Inversions

• Inversions = genetic rearrangements in which the order of genes is reversed in a chromosome segment

• Inversions do not alter the genetic content but change the linear sequence of genetic information

• At synapsis = homologous pairing, inversion loops form

Translocation is movement of a chromosomal segment to a new location in the genome

• Reciprocal translocations = exchange of genetic segments between non-homologous (unrelated) chromosomes

• There is no loss of genetic information but the functions of specific genes may be altered

• Reciprocal translocation may affect one or both pairs of chromosomes

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 Heterozygous translocation = only one pair of non-homologous chromosomes is affected

 Homozygous translocation = both pairs of non-homologous chromosomes are affected

Robertsonian Translocation

• Robertsonian translocation = fusion of two acrocentric chromosomes in the centromere region

• Translocation results in apparent loss of one chromosome in karyotype analysis

• Genetic information is lost in the tips of the translocated acrocentric chromosomes

Chromosome maps are prepared by dividing the chromosome into two regions (arms) separated by the centromere

• p = short arm (petite); q = long arm

Inversions = genetic rearrangements in which the order of genes is reversed in a chromosome segment

• Inversions do not alter the genetic content but change the linear sequence of genetic information

Week 9

One variety of extra nuclear inheritance is organelle heredity, in which DNA contained in mitochondria or chloroplasts
determines certain phenotypic characteristics of the offspring

Infectious heredity

• A second type involves infectious heredity, resulting from the symbiotic or parasitic association with a microorganism

Maternal effect

• A third is maternal effect on the phenotype, in which nuclear gene products are stored in the egg and then
transmitted through the ooplasm to the offspring

Endosymbiosis is believed to account for mitochondria and chloroplasts

Chloroplast DNA (cpDNA) is circular (like bacteria), double stranded but free of associated proteins like nuclear DNA

Mitochondrial DNA (mtDNA) is typically circular, double stranded and like cpDNA is free of associated proteins found in
nuclear DNA. (H = heavy; L = light; S = Svedberg coeff

 Replication in mitochondria is dependent on genes encoded by nuclear DNA

cpDNA and mtDNA

• Both circular and devoid of histones like nDNA

• cpDNA is much larger than mtDNA,

• cpDNA has many long non-coding sequences and duplication are present

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Human mtDNA

mtDNA is very susceptible to mutations

– Doesn't have histones to protect from mutations

– Mitochondria have high concentrations of reactive oxygen species (ROS) generated by cell respiration

• Heteroplasmy is the condition in which adult cells have a variable mixture of normal and abnormal organelles

Week 10

For a molecule to serve as the genetic material, it must be able to:

– Replicate
– Store information
– express information
– allow variation by mutation

 Some viruses have an RNA core rather than a DNA and the RNA serves as the genetic material

The central dogma of molecular genetics is that DNA makes RNA, makes proteins

Genome size

• Kilobase (kb) = 103 nucleotide pairs (double stranded) or 103 nucleotides (single stranded)

‘Alternative splicing’ is a form of gene regulation which results in the generation of alternative mRNAs from a single gene

Two types of nitrogen-containing bases comprise the chemical structure of DNA:

- Purines = adenine (A) and guanine (G) - Pyrimidine’s = thymine (T) and cytosine (C)

DNA: Chemical Comp.

• Hydrogen bonds between purines and pyrimidine’s hold the double-strand together

• Nucleoside = sugar +base

• Nucleotides = building blocks of DNA = phosphate + sugar + base

• Sugar = 5 carbon deoxyribose

• Phosphodiester bonds link sugar molecules to phosphate groups

Orientation of sugar-phosphate linkages = 5’ to 3’ as the phosphate attached to the 5’ carbon of one sugar is linked to
the 3’ carbon of the next sugar

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• DNA consists of two polynucleotide chains which run 5’ to 3’ in opposite directions = antiparallel

• DNA chains are held together by hydrogen bonds between bases

• DNA bases pair by Chargaff’s rules:

- Adenine (A) pairs with Thymine (T) - Guanine (G) pairs with Cytosine (C)

DNA is a double helix consisting of two polynucleotide chains held together by hydrogen bonds between the purines and
pyrimidine’s

• The Watson-Crick DNA model is of B-DNA, which is believed to be the biologically significant form.

• A-DNA is slightly more compact than B-DNA.

• C-DNA, D-DNA, and E-DNA are also right-handed forms of DNA that are less compact than B-DNA.

• Z-DNA forms a left-handed double helix

Retroviruses replicate in an unusual way - RNA serves as a template for synthesis of a complementary DNA by the RNA
dependent DNA polymerase called reverse transcriptase

RNA single stranded; uracil instead of T, ribose instead of deoxyribose

Three classes of cellular RNAs that function during expression of genetic information

– Messenger RNA (mRNA)

– Ribosomal RNA (rRNA)

– transfer RNA (tRNA)

DNA replication is semi-conservative =each original DNA strand is a template for a new strand complementary to the
original

DNA REP.

• Autoradiogram of replicating circular chromosome shows that DNA synthesis is bi-directional from a single start site =
origin of replication (OR)

• Replication forks = region where parental strands are separating and new strands are synthesized

• Replicon = length of DNA replication following 1 initiation event

Linear DNA replication

Replication of linear DNA molecules proceeds bidirectionally from multiple origins of replication which form replication
loops

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DnaA (protein) binds to the origin of replication and is responsible for the initial steps in unwinding the helix.

DNA polymerases catalyze the elongation of new DNA at a replication fork

DNA polymerase catalyzes DNA synthesis and requires a DNA template and all four dNTPs

DNA Synthesis

• Addition of nucleotides into growing DNA chain by DNA polymerase occurs by cleavage of two phosphate groups and
the attachment of the nucleoside monophosphate to the 3’-OH of adjacent deoxyribose sugar

DNA polymerases can only add nucleotides to the free 3’ end of a growing DNA strand.

• A new DNA strand can only elongate in the 5’->3’ direction

At the replication fork, one parental strand (3’-> 5’ into the fork), the leading strand, can be used by polymerases as a
template for a continuous complimentary strand.

• DNA polymerases cannot initiate synthesis of a polynucleotide because they can only add nucleotides to the end of an
existing chain that is basepaired with the template strand.

• To start a new chain requires a primer, a short segment of RNA.

DNA polymerase 1 removes the primers on the lagging strand and the fragments are joined by DNA ligase.

Primase, an RNA polymerase, links ribonucleotides that are complementary to the DNA template into the primer.

• Topoisomerases: nick and rejoins DNA to permit strand separation

• Helicases: unwinds DNA at replication fork

• Single-strand binding protein: stabilize DNA at replication fork preventing reformation of helix (type of helicases)

• gyrase (topoisomerase II): cleaves both strands and swivels the ends to release torsional stress

• RNA primase: initiates strand synthesis by forming RNA primer

DNA polymerase complex : catalyzes the incorporation of DNA nucleotides

• DNA ligase: joins Okazaki fragments on lagging strand

Repeated rounds of replication produce shorter and shorter DNA molecules

Telomeres protect genes from being eroded through multiple rounds of DNA replication

• Telomerase uses a short molecule of RNA as a template to extend the 3’ end of the telomere

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Week 11 - Mutations

Mutation - Change in genotype not resulting from recombination

Gene mutations are the source of new alleles (adaptation and evolution)

Spontaneous mutation: happen naturally and randomly and are usually linked to normal biological or chemical
processes in the organism

Induced mutation: result from the influence of an extraneous factor, either natural or artificial

- Radiation
- UV light
- Natural and synthetic chemical

• Mutagen = an agent that raises the freq. of mutation above the spontaneous rate.
• Mutant = a biological entity such as an allele, a cell or an individual organism

Spontaneous rates are generally very low, they vary between organisms and they also vary between genes within an
organism

Types of Mutations (Cell type)

 Somatic mutations occur in any cell except germ cells and are not heritable
 Germ-line mutations occur in reproductive cells
 Autosomal mutations occur within genes located on the autosomes,
 X-linked and Y-linked mutations occur within genes located on the X and Y

Types of Mutations Cell type cont.

• When a recessive autosomal mutation occurs in a somatic cell of a diploid organism, it is unlikely to result in a
detectable phenotype

• Inherited dominant autosomal mutations will be expressed phenotypically in the first generation

• X-linked recessive mutations arising in the gametes of a homogametic female may be expressed in hemizygous male
offspring

Types of Mutations (Expression)

• Conditional mutations: may not be evident under certain conditions

• E.g. temperature-sensitive mutations: conditional mutation whose expression depends on temperature

• At specific permissive temp. A mutant gene product may function normally while it might lose it functional capacity at
a different restrictive temp.

• Unconditional mutations: always expressed

Mutations: Effect on function

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 Loss-of-function mutation: totally nonfunctional gene product- eliminates normal function (knockout or null)
 Haploinsufficiency: with some recessive mutations the remaining dominant allele cannot produce sufficient gene
product

Hypomorphic mutation: reduces level of expression or reduces normal function (leaky)

Mutations: Effect on function

 Hypermorphic mutation: above normal level of expression (opposite to hypo) - gene product is over produced
 Gain-of-function: many are dominant and may cause expression at an abnormal time or in an abnormal place
 A specific type of gain-of-function is

– E.g. ecotypic expression = expression of a gene in an abnormal location

Mutations: molecular change

Point or base substitution is a change of one base pair to another

 May result in a new triplet code for a different amino acid: missense mutation
 May result in a triplet code for a stop codon: nonsense mutation (translation terminated prematurely)
 New triplet code still codes for the same amino acid: silent mutation

• Transversion mutations = base substitution between a purine and a pyrimidine

Four types of transition mutations

Purine to purine

 or G  A
AG

Pyrimidine to pyrimidine

T  C or C  T

Transition mutations in the third codon position do not change the amino acid that is encoded.

• The same applies to most codons ending in a purine (A & G)

Nonsense mutations change a codon to a stop codon which results in a premature termination of translation • e.g. the
stop codons are UAA, UAG or UGA & converts it to UGA a stop codon

Insertions add one or more nucleotides pairs to DNA sequence

• Deletions remove one or more nucleotide pairs from DNA sequence

• Insertions or deletions involving a multiple of 3 DNA base pairs are called in-frame since they do not alter the reading
frame of the genetic code

• Frame shift mutations shift the reading frame of the codons in the mRNA.

Any insertion or deletion that is not a multiple of three nucleotides will produce a frameshift

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Replication slippage can occur anywhere but there is hyper mutability in regions containing repeat sequences

• Purines and pyrimidine’s can exist in tautomeric forms—alternate chemical forms that differ by a single proton shift in
the molecule

• Tautomeric shifts can change the bonding structure, allowing noncomplementary base pairing

– May lead to permanent base-pair changes and mutations

Some of the most common causes of spontaneous mutation are two forms of DNA base damage:

 Depurination: loss of one of the nitrogenous bases (usually a purine A or G) in an intact double-helical DNA
molecule
 Deamination: amino group in cytosine or adenine is converted to uracil, and adenine is converted to
hypoxanthine

Deamination: amino group in cytosine or adenine is converted to uracil, and adenine is converted to hypoxanthine

Induced Mutations Arise from DNA Damage Caused by Chemicals and Radiation

Mutagens are natural or artificial agents that induce mutations

 Fungal toxins
 Cosmic rays
 Ultraviolet light
 Industrial pollutants
 Medical X rays
 Chemicals in tobacco smoke

Intercalating agents are chemicals that have dimensions and shapes that allow them to wedge between DNA base pairs,
causing base-pair distortions and DNA unwinding e.g.

– Ethidium bromide – Chemotherapeutic agents

Adduct-forming agents, mutation-causing chemicals, bind to DNA and alter its conformation, thereby interfering with
replication and repair

– Acetaldehyde

• Component of cigarette smoke

– Heterocyclic amines (HCAs)

• Cancer-causing chemicals created during cooking of meats (beef, chicken, and fish)

UV radiation creates pyrimidine dimers (two identical pyrimidine’s) that distort the DNA conformation in such a way that
errors tend to be introduced during DNA replication

• Thirty percent of mutations causing human diseases are single base-pair mutations creating nonsense mutations

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Fragile X syndrome

• 1st found in an X-linked form of mental retardation

• Particular X chromosomes fracture in cultured cells starved of DNA precursors

• called fragile X chromosomes and the form of mental retardation called fragile X syndrome’

A male carrier may be normal but his daughters often have affected children

• Transposable elements are DNA sequences capable of moving (transposing) from one location to another.

• Transposable elements are found in prokaryotes and eukaryotes

• Transposable elements are agents of mutation

• They can disrupt genes by inserting into them.

• They can promote breakage, translocations and inversion

Are grouped into families based on DNA sequence

The ClB method estimates the rate at which spontaneous recessive lethal mutations arise on the Dros. normal male X
chromosome

Week 11

• Transcription is the production of an RNA strand that is complementary in base sequence to a DNA strand = messenger
RNA (mRNA)

• RNA is synthesized from template DNA following strand separation of the double helix

Messenger RNA (mRNA) contains genetic code in triplet base codons that specify the sequence of amino acids in
proteins

The code contains "start" and "stop" signals, certain codons (nonsense codons) that are necessary to initiate and to
terminate translation

The genetic code is

• Unambiguous each triplet codes for only 1 amino acid

• Degenerate or redundant most amino acids are specified by 2, 3 or 4 different codons

mRNA serves as an intermediate in transferring genetic information from DNA to proteins. The triplet nature of the code
was revealed by frameshift mutations

Only tryptophan and methionine are encoded by a single codon

Three codons (UAG, UAA, and UGA) serve as termination codons and do not code for any amino acid

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During translation, blocks of three nucleotides, codons, are decoded into a sequence of amino acids

translation, a cell interprets a series of codons along a mRNA molecule.

• Transfer RNA (tRNA) transfers amino acids from the cytoplasm’s pool to a ribosome

AUG sometimes called the initiator codon

Transcription in eukaryotes occurs in the nucleus and is not coupled to translation

• Eukaryotic transcription requires chromatin to become uncoiled, making the DNA accessible to RNA polymerase and
other regulatory proteins. This transition is referred to as chromatin remodeling

Eukaryotic RNA polymerases rely on transcription factors (TFs) to scan and bind to DNA

• RNA polymerase II (RNP II) is responsible for a wide range of genes in eukaryotes

• RNP II promoters have a core promoter element and promoter that determine where RNP II binds to the DNA and
where it begins copying the DNA into RNA

The other three regulatory DNA sequences, proximal-promoter elements, enhancers, and silencers, influence the
efficiency or rate of transcription initiation

• The TATA box is a core promoter element that binds the TATA-binding protein (TBP) of transcription factor TFIID and
determines the start site of transcription

• Enhancers and silencers

– can be upstream, within, or downstream of the gene

– can modulate transcription from a distance

– act to increase or decrease transcription in response to cell's requirement for a gene product or at a particular time
during development or place within an organism

Introns (intervening sequences) are regions of the initial RNA transcript that are not expressed in the amino acid
sequence of the protein

• Introns are removed by splicing, and the exons are joined together in the mature mRNA

There are two main types of RNA editing prior to translation

• Substitution editing: the identities of individual nucleotide bases are altered; prevalent in mitochondria and
chloroplast RNA derived in plants

• Insertion/deletion editing: nucleotides added/deleted from the total number of bases

• Translation is the biological polymerization of amino acids into polypeptide chains

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• This process requires

– Amino acids

– Messenger RNA (mRNA)

– Ribosomes (general workbench for translation)

– Transfer RNA (tRNA)

• Ribosomes consist of proteins and ribosomal RNAs (rRNAs)

• They have a large subunit and a small subunit

• The rRNAs perform important catalytic functions associated with translation

– They promote the binding of the various molecules involved in translation and fine-tune the process

tRNAs are small in size and very stable , A tRNA has an anticodon that complementarily base-pairs with the codon in the
mRNA

3 steps of translation of mRNA (3 steps = initiation, elongation and termination)

Sickle-cell anemia is a recessive genetic disease in which afflicted individuals are homozygous for the HbS hemoglobin
allele

• Heterozygotes (HbA HbS) are carriers of the affected gene but are largely unaffected

Week 13

Quantitate traits: pea shape, colour, Drosophila eye colour etc are examples of different phenotypes

• Meristic traits are polygenic traits in which the phenotype is recorded by counting whole numbers

• Quantitative traits can be explained in Mendelian terms by many genes, each behaving individually in Mendelian
fashion, contributing to the phenotype in a cumulative or quantitative way

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