Genetics
To understand population genetics and evolution,
we’ll begin with a brief review of Mendelian
genetics (Chapter 9)
The basis of modern trait genetics is Mendel’s studies.
Mendel studied the garden pea - why?
Cheap, quick, basic traits well-known
More importantly, only two phenotypes for each
trait - flowers either purple or white, seeds
either yellow or green,…
He was also ‘lucky’ each is a single gene trait
each of the 7 traits he studied show simple
dominance - a dominant gene, when present
is always expressed in the phenotype
each shows complete penetrance - there are no
washed-out colors or incomplete expression
when he studied multi-trait phenotypes, the
pairs of traits he chose didn’t show effects of
crossing over
What did he find?
In a cross for seed colour - yellow is dominant over
green -
As long as you consider single factor crosses with
simple dominance, there are only a few possibilities:
both parents homozygous
YY
Y
y Yy
Y
Yy
y Yy
Yy
yy
all offspring will be identical
one parent homozygous, one heterozygous
YY
1/2Y 1/2Y
1/2Y 1/4YY 1/4YY
Yy
1/2y 1/4Yy 1/4Yy
offspring are half homozygous (like the
homozygous parent) and half heterozygous
What’s important is to remember that half the
gametes carry one of the parental chromosomes, and
the other half carry the other parental chromosome.
both parents heterozygous
Yy
½Y
½y
½Y ¼YY ¼Yy
Yy
½y ¼Yy ¼yy
1/4 of offspring homozygous dominant
1/2 of offspring heterozygous
1/4 of offspring homozygous recessive
Mendel found that a trait (e.g. green pea colour)
could disappear for a generation (hidden as a
recessive gene in heterozygotes), then reappear
in the next generation. He invented the terms
dominant and recessive. He proved it using a test
cross (a cross with a homozygous recessive
individual.
There are only two possible results:
all offspring identical - unknown parent homozygous
1/2 and 1/2 - unknown parent heterozygous
The results of single factor crosses led to Mendel’s
First Law - The Law of Segregation:
Each sexually reproducing organism has two alleles
for each trait. These alleles separate (segregate)
during meiosis. Only one appears in each gamete.
Now consider two factor (trait) crosses pea colour (yellow or green) and…
pea shape (round or wrinkled) together
Results of a two factor cross of heterozygotes:
9/16 dominant phenotype for both traits
3/16 dominant for one trait, recessive for the other
3/16 dominant for other trait, recessive for first one
1/16 recessive for both traits
From results of two factor crosses, Mendel formulated
the Law of Independent Assortment -
If traits are not located on the same chromosome, then
they are distributed independently in the formation of
gametes.
Now let’s consider some human traits that are
inherited simply, like Mendel’s traits in peas:
Mid-digital hair - presence (or absence) of any hair
on any finger between the middle and distal joints
I think this is a recessive.
Tongue -rolling - ability to curl your tongue into a
U shape. An autosomal dominant.
Clockwise rotation of the whorl of hair at the top
back of your head. Also autosomal dominant.
Brachydactyly - short fingers. An autosomal
dominant.
Autosomal recessive genes?
Blue eyes - presence of pigment in the iris is
dominant.
There are many others. We may be able to
determine whether a trait is dominant or recessive
from a pedigree.
e.g.
Your assignment (not one that will be graded):
For the following single gene traits in humans,
determine the phenotypes of your parents, siblings,
and, if possible, your grandparents:
tongue-rolling
hair whorl
mid-digital hair
Hitchhiker’s thumb
We could try to determine your genotype for these
traits from those of your relatives.
We use pedigrees to try to determine your genotype
or to determine whether a trait is dominant or
recessive.
Here’s a pedigree for an autosomal dominant trait:
And here’s a pedigree for a recessive trait:
Not all traits are autosomal, some are carried on
the unmatched X and Y chromosomes. These traits
are called sex-linked. Most are carried on the X.
They are inherited differently in males and females.
The male chromosome complement is XY. A male
cannot be heterozygous for an X-linked trait. There
is no way to ‘hide’ recessive traits. Therefore, sexlinked recessive traits are much more frequently
seen in males (their phenotypes) than females.
Examples of X-linked recessives:
red-green color confusion
hemophilia
Chromosome abnormalities:
fragile-X syndrome - most common genetically
caused mental retardation. A part of an X chromosome “hangs by a thread”. More common in males
than females. Effects partly determined by the parent
providing the fragile X chromosome.
arrow marks the fragile region
Retardation is more common if the fragile X came
from the mother, and is more common in males. Is
it sex-linked?
The reason for fragility is a much multiplied triplet
CGG repeat sequence (usually ~30x, in fragile X
100-1000s of times. Up to ~200 repeats there may
be no retardation. But the number of repeats seems to
increase when a woman passes the repeat segment to
her children.
So, it is sex-linked, but not in a simple Mendelian
way.
In addition to mutations that can cause cancer,
retardation, or various diseases, there can also be
abnormalities in chromosome number. This is
usually due to an error in meiosis producing either
sperm or eggs.
Because a female’s eggs only complete meiosis
year’s after it began, scientists believe that chromosome abnormalities are far more likely in older
females than in males.
The most common error in humans is trisomy 21 presence of (in whole or part) a 3rd copy of
chromosome 21. Caused by non-disjunction during
meiosis. Severity of resulting Down’s syndrome
depends in degree of trisomy.
Other relatively common chromosome number
errors occur in sex chromosomes. Why?
Non-disjunction in X:
fertilized by Y-bearing sperm - XXY
Kleinfelter’s syndrome - externally male,
but sterile, and may have some breast
development
fertilized by X-bearing sperm - XXX
trisomy X - mostly normal, fully fertile,
but may have abnormal menses
What about an egg which gets no X chromosome?
fertilized by Y-bearing sperm - -Y
aborted in early development, genes on the X are
required for survival and development
fertilized by X-bearing sperm - -X
Turner’s syndrome - thickened skin fold alongside
the neck, otherwise normal in appearance, but
female sex organs and secondary sexual characters
do not develop at puberty, sterile. Only about 2%
develop to birth, most are auto-aborted.
What about non-disjunction in Y chromosome?
if it fertilizes a normal egg - XYY
“supermale” - taller than average, possibly (??)
slightly lower IQ, some controversial evidence
of a tendency to aggressiveness and a higher
than expected presence in prison populations
Sex chromosome compliments were also used in
Olympic sex testing. How?
Females are like calico cats. In each cell (normally
randomly) one of the X chromosomes is inactivated.
It remains condensed and is bound to the nuclear
membrane. The condensed X chromosome is called
a Barr body.
Males, with only one X, need it active.
Testing involves taking a scraping from the inside of
the cheek, putting the cells on a slide, and staining
the DNA. If there is a condensed chromosome (a
Barr body), the individual is a female. None and
he is excused from competition.
This is what a Barr body looks like:
There can be problems with this determination.
A few rare females (XX) carry, by translocation,
the male determining gene from the Y on at least
one of the X chromosomes. They would appear to
be males, have approximately male muscle development, and apparently even have an enlarged, penis-like
clitoris.
And some males (XY) may, by missing a burst of
testosterone normally produced by the embryo in
utero, develop as females externally, and even to
the point of having a (non-functional) uterus.
How should society deal with these individuals?
These last questions remain unresolved, but modern
molecular testing at least tells us how the tested
individuals function.
Translocations - Pieces of chromosomes may
end up attached to different places than normal.
One example: a section of chromosome 22 attaches
to chromosome 9. Result: chronic myelocytic
leukemia, a form of cancer.
Finally, let’s look at one of the more important
point mutations important in the human genome the sickle cell trait.
Sickle cell anemia is caused by a single base change
in the DNA for a protein chain in the hemoglobin
molecule. The result is replacement of one amino
acid (a glutamic acid replaced with a valine).
There is only a slight effect if an individual is
heterozygous. Some sickling occurs if the individual
is exposed to low oxygen. About 9% of AfricanAmericans/Canadians are heterozygous.
The situation and effects are much more serious in
those who are homozygous for the altered gene.
The sickling of red blood cells when oxygen is
not bound to the hemoglobin. It causes these cells to
stick in capillaries. That causes damage in various
organs (e.g. liver, kidneys, and brain); joint problems
…
The disease used to be fatal by early adulthood. Now
people survive into middle age.
Why does a gene that causes such severe problems
persist?
There are at least two reasons:
1) Being heterozygous confers a greater resistance
to malaria. Where the gene is found at high
frequency, malaria was a severe problem, and
remains widespread.
2. Women who are heterozygous for the sickle
cell gene are more fertile (are more likely to
have children, have more children) than those
who lack the gene. Of course, those who are
homozygous for the gene will have great
difficulty with pregnancy and birth.
Therefore, even where malaria is not a problem,
e.g. North America, the gene persists. This is one
of the reasons for the importance of genetic
counselling for those who may be carriers of any
of a large number of genetic diseases.
There are tests available during pregnancy that can
spot literally hundreds of chromosome or biochemical
abnormalities.
Amniocentesis - amniotic fluid from within placenta
extracted, cells in it cultured, tested for chromosome
abnormalities and/or suspected biochemical problems
Performed at 15-16 weeks into pregnancy.
Chorionic villus sampling - cells from the fetal part of
placenta extracted and tested. This test can be
performed earlier in pregnancy (6-12 weeks)
Now back to the inheritance and expression of
human traits Mendelian genetics is relatively simple. The
situation for most human traits is not quite that
simple. There are complications.
Expressivity - the same gene may be expressed
differently in two individuals. Reasons may
include environment, genetic background (the
other genes), …
Penetrance - the likelihood that an individual
carrying a dominant gene will express it. Some
traits with incomplete penetrance will be
expressed in only a fraction of individuals.
Pleiotropy - one gene may affect many traits.
Remember all those effects of sickle cell trait. The
same sort of thing occurs with a 3 base deletion in
the gene for a transmembrane protein that pumps
Cl- out of cells. The defective protein leads to
cystic fibrosis, affecting lungs, sweat, digestive
glands (particularly the pancreas), and sex organs.
Most (virtually all) traits are polygenic. What we see
in the phenotype is the joint result of the actions of
2 or more genes. Eye color results from 2 genes one determines whether pigment will be produced;
the other determines how much.
Multiple alleles - the Mendelian traits we looked at
had only two alternative alleles. Many traits have
more than 2 possible versions. The classic example
is blood types. There are 3 alleles involved in ABO
blood group determination: IA , IB , and i.
These alleles determine the presence of antigenic
proteins on the surfaces of red blood cells. IA causes
the presence of A-type glycoprotein on cell surfaces.
IB causes B-type glycoprotein. i does not cause an
effective antigen to be present.