fluorescence
in situ
hybridization
(FISH)
we can show that the factors—genes—are
located on chromosomes
The location of a
particular gene
can be seen by
tagging isolated
chromosomes
with a fluorescent
dye that highlights
the gene
Gametes have a single set of chromosomes
An organism’s life
cycle is the sequence
of stages leading
– from the adults of one
generation
– to the adults of the
next.
▪ Humans and many
animals and plants are
diploid, with body cells
that have
– two sets of
chromosomes,
– one from each parent.
Duplication of chromosomes is central
component of mitosis and meiosis
Sorts new sets of chromosomes
into the resulting pair of daughter
cells
For reproduction of single-celled
organisms
For growth of multicellular
organisms from a fertilized egg
into an adult
To repair and replacement of
cells
For sperm and egg production
Origins of Genetic Variation Among Offspring
The behavior of chromosomes during meiosis and
fertilization is responsible for most of the variation
that arises in each generation
▪ Three mechanisms contribute to genetic variation:
– Random fertilization (eg. many sperm competing to
fertilize egg, or many sperm and many eggs)
– Independent assortment of chromosomes
– Crossing over
Independent Assortment of Chromosomes
Homologous pairs of
chromosomes orient
randomly at
metaphase I of
meiosis
▪ In independent
assortment, each pair
of chromosomes
sorts maternal and
paternal homologs
into daughter cells
independently of the
other pairs
The number of combinations possible when
chromosomes assort independently into gametes is
2n, where n is the haploid number
▪ For humans (n = 23), there are more than 8 million
(223) possible combinations of chromosomes
▪ Means that the majority of our gametes are unique
First evidence of chromosomal basis for
inheritance
Thomas Hunt Morgan chose to study Drosophila
melanogaster, a common species of fruit fly
– They produce many offspring
– A generation can be bred every two weeks
– They have only four pairs of chromosomes
First evidence of chromosomal basis for
inheritance
Morgan noted wild type, or normal, phenotypes that
were common in the fly populations
▪ Traits alternative to the wild type are called mutant
phenotypesMorgan mated male flies with white eyes (mutant) with
female flies with red eyes (wild type)Morgan reasoned that the white-eyed mutant allele must
be located on the X chromosome
Chromosomes determine sex in many
species
Many animals have a pair of sex chromosomes,
– designated X and Y,
– that determine an individual’s sex.
▪ In mammals,
– males have XY sex chromosomes,
– females have XX sex chromosomes,
– the Y chromosome has 78 genes mainly related to the
development of testes
– The X chromosome contains 1,100 genes involved in
many aspects of physiology
The Y chromosome has genes required for the
development of testes
Sex determining region
of Y gene (SRY) is
solely responsible for
testes development
An absence of the Y
chromosome or SRY
gene allows ovaries to
develop
Other systems of sex
determination
The X-0 system
The Z-W system
The haplo-diploid system
In some animals, environmental temperature
determines the sex.
– For some species of reptiles, the temperature at which
the eggs are incubated during a specific period of
development determines whether the embryo will develop
into a male or female
Global climate change may therefore impact the sex ratio
of such species (ie. more female turtles born)
Sex-linked genes exhibit a unique pattern of
inheritance
Sex-linked genes are located on either of the sex
chromosomes.
▪ The X chromosome carries many genes unrelated to
sex.
▪ Most sex-linked human disorders are
– due to recessive alleles and
– seen mostly in males
Color blindness is an X-linked recessive trait
All daughters will receive color blindness allele from
colorblind father
½ sons will be colorblind if mother carries colorblind
allele
Only a daughter born to parents who both carry color
blindness allele could be colorblind
Hemophilia – the Royal Disease:
characterized by excessive bleeding because
hemophiliacs lack one or more of the proteins
required for blood clotting
The Y chromosome provides clues about
human male evolution
The Y chromosome provides
clues about human male
evolution because
– Y chromosomes are passed intact
from father to son and
– mutations in Y chromosomes can
reveal data about recent shared
ancestry.
– 8% of males in Central Asia carry
same mutation
* Males (XY) – One X chromosome
* Females (XX) – Two X chromosomes
Do females make twice as much as
males of the products encoded on the
X chromosome?
Why not? - Because one of X chromosomes is
inactivated
NO!
Germline tissue
(produces gametes) express both X
chromosomes
somatic tissues
of females are a mosaic, some
express maternal X chromosome and others the paternal X
chromosome
X Inactivation in Female Mammals
In mammalian females, one of the two X chromosomes in each cell is
randomly inactivated during embryonic development – condenses into a Barr body
X-inactive specific transcript (XIST) is activated on
chromosome that will be inactivated
XIST mRNA covers the chromosome
Chromosomal DNA then has methyl (CH3) groups
attached to it to inactivate it
Accidents during meiosis can alter
chromosome number or structure
Observed rare
occasions when a white
eyed female fly would
emerge in a cross
between a red-eyed
male and white-eyed
female
▪ Explanation was that
female offspring must
have inherited two white
alleles instead of the
just one from the mother
▪ Nondisjunction is the
failure of chromosomes
or chromatids to
separate normally
during meiosis
Accidents during meiosis can alter
chromosome number or structure
This can
happen during
– meiosis I, if both
members of a
homologous pair go to
one pole or
– meiosis II if both sister
chromatids go to one
pole.
▪ Fertilization after
nondisjunction yields
aneuploid zygotes with
altered numbers of
chromosomes.
karyotype
is an ordered display of magnified
images of an individual’s chromosomes arranged in
pairs.A karyotype is produced by staining chromosomes with dyes
that stain DNA differentially based on DNA packing and base
composition
An extra copy of chromosome 21 causes Down syndrome
Trisomy 21, called Down
syndrome, produces a
characteristic set of
symptoms
– involves the
inheritance of three
copies of
chromosome 21
– is the most common
human chromosome
abnormality.
Genes on the same chromosome tend to be
inherited together
Bateson and Punnett crossed F1 plants that did not show a
9:3:3:1 ratio in the F2 generation.What they found was
an example of
linked genes
* are located close
together on the
same
chromosome
* tend to be
inherited together
* do not follow
Mendel’s law of
independent
assortment
Instead, they observed
a small number of
Purple Round and Red
Long plant
Crossing over produces new combinations of
alleles
Crossing over between homologous chromosomes
produces new combinations of alleles in gametes.
▪ Linked genes can be separated by crossing over, forming
recombinant gametes.
▪ The percentage of recombinant offspring is the
recombination frequency
Geneticists use crossover data to map
genes
The greater the distance between two genes on a chromosome,
the higher the likelihood that a crossing event could occur
between them(aka recombination)
Recombination frequencies can thus be used to map the relative
position of genes on chromosomes.
Genomic imprinting is unusual in that only one
inherited allele is expressed
For a few mammalian traits, the phenotype depends
on which parent passed along the alleles for those
traits
▪ Genomic imprinting involves the silencing of certain
genes depending on which parent passes them onInheritance of a mutant Igf2 gene from father results in dwarf mouse
▪ Inheritance of a mutant Igf2 gene from mother results in normal size mouse
Imprinting is the result of the methylation (addition of —CH3 groups) of
cysteine nucleotides (ie. similar to XIST silencing)
▪ Most ~100 imprinted genes are critical for embryonic developmentchromosome Normal Igf2 allele
is not expressed.
Normal-sized mouse
(wild type)
(a) Homozygote
Mutant Igf2 allele
inherited from mother
Mutant Igf2 allele
inherited from father
Normal-sized mouse (wild type)
Normal Igf2 allele
is expressed.
Dwarf mouse (mutant)
Mutant Igf2 allele
is expressed.
Mutant Igf2 allele
is not expressed.
(b) Heterozygotes
Normal Igf2 allele
is not expressed.
▪ Inheritance of a mutant Igf2 gene from father results in dwarf mouse
▪ Inheritance of a mutant Igf2 gene from mother results in normal size mouse
Inheritance of Organelle Genes
- Mitochondria,
chloroplasts, and other plant plastids carry small circular
DNA molecules
▪ Extranuclear genes are inherited maternally
because the zygote’s cytoplasm comes from the
egg
Controversial “mitochondrial donation” treatment
Some defects in mitochondrial genes prevent cells from
making enough ATP and result in diseases such as
mitochondrial myopathy
