1. health and fitness
2. disease

Chapter 10: Patterns of inheritance
Life Science 141
Dr Stephen Boatwright
Department of Biodiversity and Conservation Biology
Chromosomes are packets of genetic information
• A gene is a portion of DNA whose sequence of nucleotides encodes a protein
• Each gene can exist as one or more alleles or alternative forms of the gene
• The DNA in the nucleus is divided among multiple chromosomes which are long
strands of DNA associated with proteins
• A diploid cell contains two sets of chromosomes with one set inherited from each
parent
• Humans contain 23 pairs of chromosomes, with 22 of these pairs being autosomes
(chromosomes that are the same for both sexes) and a single pair of sex
chromosomes which determines whether an individual is male or female (female two
X chromosomes and male one X and one Y chromosome)
• A homologous pair of chromosomes look alike and have the same sequence of
genes in the same positions
• They may or may not carry the same alleles
• Since each homolog comes from a different parent each person inherits two alleles
for each gene in the human genome
• A gene’s locus is its physical location on the chromosome
• Meiosis is a specialized form of cell division that occurs in diploid germ cells and
gives rise to haploid cells, each containing just one set of chromosomes
• In humans these cells are gametes – sperm or egg cells
• Fertilization unites the gametes from two parents producing the first cell of the next
generation
• Gametes convey the chromosomes from one generation to the next and are
important in inheritance
Homologous Chromosomes
Gregor Mendel
Mendel’s experiments uncovered basic laws of inheritance
Why peas?
• Mendel, the son of a farmer and a brilliant mathematician was a monk in Austria and
he worked with the garden pea plant (Pisum sativum) which is capable of both selffertilization and cross-fertilization
• They are easy to grow, develop quickly, produce many offspring and it is easy to
control which plants mate with which
Dominant alleles appear to mask recessive alleles
• Mendel’s first experiments dealt with single traits that have two expressions
• He set up all possible combinations of crosses
• He noted that some plants were always true-breeding or self-fertilization always
produced offspring identical to the parent plant
• The crosses involving some traits, however, produced more variable offspring
• They were sometimes true-breeding but in other cases the offspring were mixed
• Sometimes some traits vanished in one generation, only to reappear in the next
• One trait seemed to obscure the other
• Mendel called the masking trait dominant and the trait being masked recessive
• A dominant allele is one that exerts its effects whenever it is present and a
recessive allele is one whose effect is masked if a dominant allele is also present
• When a gene has two alleles it is common to symbolize the dominant allele with a
capital letter and the recessive allele with the corresponding lowercase letter
Mendel’s experiments uncovered basic laws of inheritance
For each gene, a cell’s two alleles may be identical or different
• For a given gene a diploid cell’s two alleles may be identical or different
• The genotype expresses the genetic makeup of an individual, written as a pair of
letters representing the alleles
• individual that is homozygous for a gene has two identical alleles, meaning that both
parents contributed the same gene version
• If both the alleles are dominant the individual’s genotype is homozygous dominant
(e.g. YY) and if both are recessive the individual is homozygous recessive (e.g. yy)
• individual with a heterozygous genotype has two different alleles for each gene (e.g.
Yy)
• The two parents each contributed different genetic information
• The organism’s genotype is distinct from its phenotype or observable characteristics,
e.g. flower colour, stem length etc.
• Mendel’s observations that only some yellow-seeded pea plants were true breeding
arises from two possible genotypes for the yellow phenotype (homozygous dominant
and heterozygous)
• All homozygous plants are true-breeding because all their gametes contain the same
allele
• Heterozygous plants are not true-breeding because they may pass on either the
dominant or the recessive allele
• A wild-type allele, genotype or phenotype is the most common form of a gene in a
population
• A mutant allele, genotype or phenotype is a variant that arises when a gene
undergoes a mutation
Mendel’s experiments uncovered basic laws of inheritance
Every generation has a name
• The purebred P generation (for ‘parental’) is the first set of individuals being mated;
the F1 generation or first filial generation is the offspring from the P generation
• The F2 generation is the offspring of the F1 plants and so on
• See Table 10.1 pg. 203 in textbook for summary of terms
Fruit and Flower of the Garden Pea
Garden Pea Traits
Studied by Mendel
The two alleles of each gene end up in different gametes
Monohybrid crosses track the inheritance of one gene
A monohybrid cross is a mating between two individuals that are both heterozygous for
the same gene. A diagram called a Punnett square uses the genotype of the parents to
reveal which allele combinations the offspring may inherit
e.g. Pure breeding tall plants crossed with true breeding dwarf plants yielded only tall
plants (F1). Tallness is thus dominant and dwarfism is recessive
In the second generation tall plants from F1 were crossed with other plants of the F1
generation
When these tall plants (P2) are crossed with themselves (self-fertilized) some of the
offspring (F2) were tall and some short in a 3:1 ratio
From these results Mendel concluded that the unit for dwarfism did not disappear in the
F1 generation but that it was overshadowed by the unit for tallness. In the next
generation the dwarfism will again be expressed
Mendel’s Law of Segregation: As stated earlier Mendel came to the conclusion that in
adults we get two units for each trait. When a gamete is formed the two units separate
resulting in each gamete receiving only one unit. The above cross can thus be
represented as follows (remember that meiosis leads to the formation of four gametes):
P1
TT
Gametes: All
All
P1
Tt
T
T
tt
All
T
F1
Gametes
x
t
Tt
x
t
t
Tt
Gam
T
T
t
t
We can now determine the offspring using the so-called Punnett square. This is an
easier way of visualizing the offspring. The gametes of the one parent are written
across at the top and that of the other along the left-hand side
In the first table there are 12 tall plants (at least one T), and 4 dwarf plants (tt), which
gives us a ratio of 3:1
NB. When we have two or more gametes with the same allele, i.e. all dominant or all
recessive, we only need to write down the one gamete as the ratio will remain the same
Laws of Probability
When tossing a coin there is always a 50:50 chance of it being heads or tails. In the
same way the child of a parent heterozygous for a specific trait, e.g. Aa, will have a
50:50 chance of having either A or a
However, if we have a cross between Aa x Aa the child will inherit an allele from each
parent. In determining the probability that a child will inherit a specific set of two alleles
the law of probability states that the probability of two or more independent events
occurring together is the product (multiplication) of their chances of occurring separately
The chance of AA = ½ x ½ = ¼
The chance of Aa = ½ x ½ = ¼
The chance of aA = ½ x ½ = ¼
The chance of aa = ½ x ½ = ¼
From the above we can see that the dominant phenotype can occur ¾ times (75%), and
the recessive one ¼ times (25%)
Punnett Square Showing
Earlobe Inheritance Patterns
• Punnett square named after R.C. Punnett
• Punnett square for monohybrid cross has
4 squares and for a dihybrid cross 16
squares etc.
• Expected genotypes ¼ EE, ½ Ee, ¼ ee
or 1:2:1 genotypic ratio
• ¾ have unattached earlobes and ¼
attached earlobes, 3:1 phenotypic ratio
Test crosses
• A test cross is a mating between an individual of unknown genotype and a
homozygous recessive individual
• If all the offspring of this cross displays the dominant trait the unknown must be
homozygous dominant, and when some of the offspring shows the dominant trait and
others the recessive we know that the unknown is heterozygous
• In the case of the tallness experiments of Mendel F1 plants were crossed with true
breeding dwarf plants. Half the plants were tall and half were dwarf and this indicated
that the F1 plants were heterozygous
• Individuals with the recessive phenotype always have the homozygous recessive
genotype
• Individuals with the dominant phenotype have an indeterminate genotype: may be
heterozygous (Tt) or homozygous dominant (TT)
• Test cross determines the genotype of the individual having the dominant
phenotype
One-Trait Test Cross
Unknown is Heterozygous
One-Trait Test Cross
Unknown is Homozygous Dominant
Meiosis explains Mendel’s Law of Segregation
• Mendel used his data to conclude that genes occur in alternative versions or alleles
• He further determined that each individual inherits two alleles for each gene and that
these alleles may be the same or different
• He deduced his law of segregation which states that the two alleles of each gene are
packaged into separate gametes; that is they segregate or move apart from each
other during gamete formation
• During meiosis I homologous pairs of chromosomes separate and move to opposite
poles of the cell
• A plant of genotype Yy therefore produces equal numbers of gametes carrying Y or y,
whereas YY a plant produces only Y gametes
• When gametes from the two parents meet at fertilization, they combine at random
• About 50% of the time both gametes carry Y, the other 50% of the time one
contributes Y and the other y
Genes on different chromosomes are inherited independently
• A dihybrid cross is a mating between individuals that are each heterozygous for two
genes
• Mendel also performed experiments where he followed the inheritance pattern of two
traits simultaneously, e.g. plants that differed in colour and height
• In these dihybrid crosses each F1 offspring inherit two gene pairs each consisting of
non-identical alleles
• Plants, true-breeding for both green pods and tallness were bred with plants truebreeding for yellow pods and dwarfism
• All the F1 plants had green pods and were tall
• In the F2 generation 4 different combinations were obtained due to the fact that the
two characteristics behave independently of one another
• It does not matter with which allele for pod colour the gamete ends up with it will have
a 50:50 chance of getting either of the alleles for height (refer to independent
assortment in meiosis)
• Due to Mendel's ignorance of chromosomes he deduced that the units for the
different traits were assorting independently into gametes
• Mendel’s law of independent assortment states that during gamete formation, the
segregation of the alleles for one gene does not influence the alleles for another gene
Two-Trait (Dihybrid) Cross
• In determining the possible outcomes of
crosses between two parents
heterozygous for both traits we can
again use the law of probability, e.g. Tt
for tall plants and Gg for yellow pods
Tall plants will be ¾ times,
Dwarf plants will be ¼ times,
Green pods will be ¾ times, and
Yellow pods will be ¼ times.
Thus,
Tall, green pods = ¾ x ¾ = 9/16
Tall, yellow pods = ¾ x ¼ = 3/16
Dwarf, green pods = ¼ x ¾ = 3/16
Dwarf, yellow pods = ¼ x ¼ =
1/16
Two-Trait Test Cross
• To determine if an individual is homozygous
dominant or heterozygous for either of the two
traits. Represent genotype as L_G_
• Crossed with an individual with recessive
phenotype
• A long-winged, grey bodied fly heterozygous for
both traits will form four different types of gametes
• ¼ have long wings and grey body; ¼ have long
wings and black body; ¼ have short wings and
grey body; ¼ have short wings and black body
• 1:1:1:1 phenotypic ratio
• The presence of offspring with short wings and a
black body shows that the L_G_ fly is
heterozygous for both traits LlGg
• If the L_G_ fly is homozygous for both traits no
offspring will have short wings or a black body
when the fly is crossed with one that is recessive
for both
Genes on different chromosomes are inherited independently
• Linked genes are carried on the same chromosome and they are therefore inherited
together. Unlike genes on different chromosomes they do not assort independently
during meiosis
• T H Morgan (1910) and his co-workers worked with the fruit fly Drosophila
melanogaster and they confirmed that each gene has a specific location on a
chromosome. The fruit fly normally has red eyes but in his experiments Morgan
encountered a male with white eyes which is a mutant form. When they crossed a
white-eyed male with a wild-type (normal) red-eyed female all the offspring had red
eyes giving him the impression that red eyes were dominant over white eyes in
agreement with the results Mendel had in his experiments
• When these offspring were crossed with one another all the females and half the
males had red eyes, and the rest of the males were white-eyed
• This could have been an indication that females could not have white eyes. A test
cross involving red-eyed females of the F1 generation followed giving equal ratios of
red- and white-eyed for both females and males. The only explanation for this was
that the gene of eye colour had to be on the X-chromosome, and called X-linked.
• The above provided the first clear evidence that genes are located on specific
chromosomes
• NB. When we state that a gene is X-linked we must write down the X and the Y
to indicate whether the specific individual is female or male.
X-Linked Inheritance
Linkage groups and crossing-over
As stated earlier the traits that Mendel studied were the results of genes located on
different chromosomes
This then obviously resulted in these genes being independently assorted from one
another
However, we do find that chromosomes carry different genes for different traits
It has been found that many genes located on a specific chromosome tend to end up
together in the same gamete; they are called linkage groups (found on the same
chromosome)
Crossing-over, i.e. the exchange of genetic material between nonsister chromatids
during meiosis, can affect the way linkage groups are passed on from one generation to
the next.
Morgan found that the genes for eye colour and wing shape were on the same
chromosome (X) and that they tend to be inherited together, i.e. red eyes with normal
wings, and white eyes with vestigial (underdeveloped) wings
However, in some of his crosses he found progeny/offspring with red eyes and vestigial
wings, and white eyes and normal wings
This is the result of crossing over
The further apart genes are located on a specific chromosome the greater the chances
of crossing-over taking place
Gene expression can appear to alter Mendelian ratios
In his studies Mendel encountered traits that had clear dominance or recessive forms.
However, we do encounter situations where there is no such clear-cut dominance to be
observed, i.e. the offspring formed do not resemble either parent in appearance. Thus,
although we get three different genotypes we will only get two different phenotypes
Incomplete dominance: When true-breeding red snapdragons (flower plant) are crossed
with true-breeding white ones the F1 plants are all pink-flowered
(To prevent confusion between complete dominance and incomplete dominance we
write both alleles in the capital form, but we prime or number the one set/homologue,
e.g. RR for red, and R/ R/ or R1R2 for white instead of Rr. Pink will thus be RR/)
The F2 generation will have three possible colours, i.e. red, pink and white. The F2 thus
have three different phenotypes and three different genotypes
Incomplete Dominance
Gene expression can appear to alter Mendelian ratios
Codominace: In this case we find that no allele in a gene allele pair is completely
dominant over the other one. However, unlike incomplete dominance where the
heterozygote expresses a mixture of the two extremes, in codominance the
heterozygote displays characteristics of both alleles equally. The best quoted example is
in the case of blood groups in humans. Landsteiner (1900) discovered the multiple allele
ABO blood group in humans. Any individual will, however, have only two of the alleles
present
Glycolipids on the membrane of the red blood cells determine whether donated blood is
compatible with that of the recipient. The following table represents the different blood
groups and their compatibility with other blood groups
Blood
Type
Corresponding
to
Antigens on Red Cells
Antibodies in Serum
Genotype
Reactions to Anti-A
Reactions to Anti-B
O
Anti-A and Anti-B
Ii (OO)
-
-
A
Anti-B
IAIA or Iai (AA or AO)
+
-
B
Anti-A
IBIB or Ibi (BB or BO)
-
+
AB
None
IA IB (AB)
+
+
Inheritance of Blood Type
Terminology
• Pleiotropy
– A gene that affects more than one characteristic of an
individual
– Sickle-cell (incomplete dominance)
– Marfan syndrome – abnormality in fibrillin production
• Epistasis
– A gene at one locus interferes with the expression of a gene
at a different locus
– Human skin color (polygenic inheritance)
– Flower colour in sweet peas
Genetic disorders
Autosome - Any chromosome other than a sex chromosome
Genetic disorders caused by genes on autosomes are called
autosomal disorders
Some genetic disorders are autosomal dominant
An individual with AA has the disorder
An individual with Aa has the disorder
An individual with aa does NOT have disorder
Other genetic disorders are autosomal recessive
An individual with AA does NOT have disorder
An individual with Aa does NOT have disorder, but is a
carrier
An individual with aa DOES have the disorder
Autosomal Recessive Pedigree Chart
Autosomal Dominant Pedigree Chart
Autosomal recessive disorders
• Tay-Sachs Disease
– Progressive deterioration of psychomotor functions through
deterioration of nerve cells
• Cystic Fibrosis
– Mucus in bronchial tubes and pancreatic ducts is particularly
thick and viscous
• Phenylketonuria (PKU)
– Lack enzyme for normal metabolism of phenylalanine
– Phenylalanine builds up to toxic levels, can affect brain
function and affect other body systems
Cystic Fibrosis Therapy
33
Autosomal dominant disorders
• Neurofibromatosis
– Tan or dark spots develop on skin and darken
– Small, benign tumors may arise from fibrous nerve coverings
or can be more severe and affect the brain
– Several types
• Huntington Disease
– Neurological disorder (neurodegenerative)
– Progressive degeneration of brain cells, mental ability and
behaviour
• Severe muscle spasms
• Personality disorders
A Victim of Huntington Disease
35
Huntington Disease:
Normal and Diseased Brain
36
Polygenic inheritance
• Occurs when a trait is governed by two or more genes having
different alleles
• Each dominant allele has a quantitative effect on the phenotype
• These effects are additive
• Result in continuous variation of phenotypes
Height in Human Beings
38
Frequency Distributions in
Polygenic Inheritance
39
Environment and Phenotype:
Himalayan Rabbits
40
X-linked alleles
• Genes carried on autosomes are said to be autosomally linked
• Genes carried on the female sex chromosome (X) are said to
be X-linked (or sex-linked)
• X-linked genes have a different pattern of inheritance than
autosomal genes have
– The Y chromosome is blank for these genes
– Recessive alleles on X chromosome:
• Follow familiar dominant/recessive rules in females (XX)
• Are always expressed in males (XY), whether dominant
or recessive
• Males said to be monozygous for X-linked genes
Eye colour in fruit flies
• Fruit flies (Drosophila melanogaster) are common subjects for
genetics research
• They normally (wild-type) have red eyes
• A mutant recessive allele of a gene on the X chromosome can
cause white eyes
• Possible combinations of genotype and phenotype:
XRXR
XRXr
XrXr
XRY
XrY
Genotype
Homozygous Dominant
Heterozygous
Homozygous Recessive
Monozygous Dominant
Monozygous Recessive
Phenotype
Female
Red-eyed
Female
Red-eyed
Female
White-eyed
Male
Red-eyed
Male
White-eyed
X-Linked Inheritance
Human X-linked disorders: Red-Green colour blindness
• Colour vision in humans:
– Depends three different classes of cone cells in the retina
– Only one type of pigment is present in each class of cone
cell
• The gene for blue-sensitive is autosomal
• The red-sensitive and green-sensitive genes are on the X
chromosome
• Mutations in X-linked genes cause RG colour blindness:
– All males with mutation (XbY) are colourblind
– Only homozygous mutant females (XbXb) are
colourblind
– Heterozygous females (XBXb) are asymptomatic
carriers
Red-Green Colorblindness Chart
45
X-Linked Recessive Pedigree
46
Human X-linked disorders: Muscular Dystrophy
• Muscle cells operate by release and rapid sequestering of
calcium
• Protein dystrophin required to keep calcium sequestered
• Dystrophin production depends on X-linked gene
• A defective allele (when unopposed) causes absence of
dystrophin
– Allows calcium to leak into muscle cells
– Causes muscular dystrophy
• All sufferers male
– Defective gene always unopposed in males
– Males die before fathering potentially homozygous recessive
daughters
Human X-linked disorders: Hemophilia
• “Bleeder’s Disease”
• Blood of affected person either refuses to clot or clots too
slowly
– Hemophilia A – due to lack of clotting factor IX
– Hemophilia B – due to lack of clotting factor VIII
• Most victims male, receiving the defective allele from carrier
mother
• Bleed to death from simple bruises, etc.
• Factor VIII now available via biotechnology
Hemophilia Pedigree
49
Human X-linked disorders: Fragile X syndrome
• Due to base-triplet repeats in a gene on the X chromosome
• CGG repeated many times
– 6-50 repeats – asymptomatic
– 230-2,000 repeats – growth distortions and mental
retardation
• Inheritance pattern is complex and unpredictable
Gene linkage
• When several genes of interest exist on the same chromosome
• Such genes form a linkage group
– Tend to be inherited as a block
– If all genes on same chromosome:
• Gametes of parent likely to have exact allele combination
as gamete of either grandparent
• Independent assortment does not apply
– If all genes on separate chromosomes:
• Allele combinations of grandparent gametes will be
shuffled in parental gametes
• Independent assortment working
Linkage Groups
52
Constructing a chromosome map
• Crossing-over can disrupt a blocked allele pattern on a
chromosome
• Affected by distance between genetic loci
• Consider three genes on one chromosome:
– If one at one end, a second at the other and the third in the middle
• Crossing over very likely to occur between loci
• Allelic patterns of grandparents will likely to be disrupted in parental
gametes with all allelic combinations possible
– If the three genetic loci occur in close sequence on the chromosome
• Crossing over very UNlikely to occur between loci
• Allelic patterns of grandparents will likely to be preserved in parental
gametes
• Rate at which allelic patterns are disrupted by crossing over:
– Indicates distance between loci
– Can be used to develop linkage map or genetic map of chromosome
Crossing Over
54
Complete vs. Incomplete Linkage
55
Chromosome number: Polyploidy
• Polyploidy
– Occurs when eukaryotes have more than 2n chromosomes
– Named according to number of complete sets of
chromosomes
– Major method of speciation in plants
• Diploid egg of one species joins with diploid pollen of
another species
• Result is new tetraploid species that is self-fertile but
isolated from both “parent” species
• Some estimate 47% of flowering plants are polyploids
– Often lethal in higher animals
Chromosome number: Aneuploidy
• Monosomy (2n - 1)
– Diploid individual has only one of a particular chromosome
– Caused by failure of synapsed chromosomes to separate at
Anaphase I (nondisjunction)
• Trisomy (2n + 1) occurs when an individual has three of a
particular type of chromosome
– Diploid individual has three of a particular chromosome
– Also caused by nondisjunction
– This usually produces one monosomic daughter cell and one
trisomic daughter cell in meiosis I
– Down syndrome is trisomy 21
Nondisjunction
58
Trisomy 21
59
Chromosome number: abnormal sex chromosome number
• Result of inheriting too many or too few X or Y chromosomes
• Caused by nondisjunction during oogenesis or
spermatogenesis
• Turner Syndrome (XO)
– Female with single X chromosome
– Short, with broad chest and widely spaced nipples
– Can be of normal intelligence and function with hormone
therapy
Chromosome number: abnormal sex chromosome number
• Klinefelter Syndrome (XXY)
– Male with underdeveloped testes and prostate; some breast
overdevelopment
– Long arms and legs; large hands
– Near normal intelligence unless XXXY, XXXXY, etc.
– No matter how many X chromosomes, presence of Y
renders individual male
Turner and Klinefelter Syndromes
62
Chromosome number: abnormal sex chromosome number
• Poly-X females
– XXX simply taller & thinner than usual
– Some learning difficulties
– Many menstruate regularly and are fertile
– More than 3 Xs renders severe mental retardation
• Jacob’s syndrome (XYY)
– Tall, persistent acne, speech & reading problems
Abnormal chromosome structure
• Deletion
– Missing segment of chromosome
– Lost during breakage
• Translocation
– A segment from one chromosome moves to a nonhomologous chromosome
– Follows breakage of two nonhomologous chromosomes and
improper re-assembly
Abnormal chromosome structure
• Duplication
– A segment of a chromosome is repeated in the same
chromosome
• Inversion
– Occurs as a result of two breaks in a chromosome
• The internal segment is reversed before re-insertion
• Genes occur in reverse order in inverted segment
Deletion, Translocation,
Duplication, and Inversion
66
Inversion Leading to
Duplication and Deletion
67
Abnormal chromosome structure
• Deletion Syndromes
– Williams syndrome - Loss of segment of chromosome 7 –
intellectual disability, distinctive behavioural and facial
characteristics and cardiac problems
– Cri du chat syndrome (cat’s cry/Lejeune’s syndrome) - Loss
of segment of chromosome 5 – characteristic cat-like sounds
made by affected children due to problems with larynx and
nervous system
• Translocations
– Alagille syndrome – affects liver, heart, kidneys and other
body systems due to organ abnormalities
– Some cancers
Williams Syndrome
69
Alagille Syndrome
70
Microevolution
• All the members of a single species occupying a particular area – population
• Evolution that occurs within a population is called microevolution and results in
changes in the relative frequencies of alleles in a population
• In population genetics, the various alleles at all the gene loci in all individuals make
up the gene pool
• The Hardy-Weinberg principle:
– Allele frequencies in a population will remain
constant assuming:
• No Mutations
• No Gene Flow
• Random Mating
• No Genetic Drift
• No Selection
Therefore conditions that can cause deviation from this
equilibrium are mutations, gene flow, non-random mating,
genetic drift and natural selection
Genetic Drift
Founder Effect
Calculating Gene Pool Frequencies
Using the Hardy-Weinberg Equation
Sixteen percent of a population is unable to taste the chemical PTC. These non-tasters
are recessive for the tasting gene.
1) What percentage of individuals in the population are tasters?
2) What is the frequency of the dominant and recessive allele?
3) What percentage of the population are heterozygous for the trait?
The delta-32 mutation, a recessive gene, gives humans protection from HIV infection.
The allele frequency in a town in Sweden is 20%.
1) What percentage of the population have two copies of the gene and are therefore
immune to HIV?
2) What percentage of the population are less susceptible to the disease since they are
heterozygous?