What are they?
of Mendelian Inheritance
nutrition, sunlight etc.)
by known gene loci
-- zero "linkage"
alleles; Null alleles
Dihybrid -- Dihybrid Cross
cross or Back
cross (when are these the same -- and when not?)
Genetics Practice from
a course at MIT.
Genetics: describes interesting horse phenotypes and genotypes,
crosses and results
Online Mendelian Inheritance in Man: a
professional physician’s reference on inherited diseases
What are they?
a particular version of a given DNA sequence. "Allele" is a
term, implying more than one possible version or copy, like different
of a book. Like editions of a book, all existing alleles result
a process of change, either gradual or drastic change.
be more than two
possible alleles for a given gene locus (but only
two at a time, in a given diploid individual.)
can mean many different possible combinations for
An example of multiple alleles is human blood type -- A or B alleles
a blood serum protein, whereas the O allele makes no protein ( a null
Gene loci which confer traits of tissue type may have 20 or more
from evolution, the process of natural selection.
be created by molecular genetics.
natural and artificial
alleles can be used by the scientist for breeding purposes.
Alleles can be
as DNA polymorphisms, using restriction digest and gel electrophoresis
(see Week 7).
An allele may
to an inherited disease--a clue as to the gene locus defective in the
four alleles (M1-M4) is linked to this disease?
Is the disease
to be dominant or recessive?
report on an inherited disease in her family, see Tuberous
expressing gene products, which are either mRNA and protein, or
a functional RNA. But how they determine a "visible
trait" is not simple. Consider this:
fly eyes have two pigments, brown and scarlet. Normal flies make
pigments, but a strain with defective gene B has brown eyes, and a
with defective gene S has scarlet eyes.
the wild type, WHICH GENE (B or S) makes which pigment (brown or
practice, the most
common "new" alleles (arising out of mutation) are often named for a
resulting from the absence of their gene product. Thus the allele
for a gene producing scarlet pigment is named "brown" for the brown eye
in the absence of scarlet pigment.
or loss of pigmentation, a very common phenotype observed in many
of animals and plants. Alleles can confer loss of pigmentation in
two different ways:
Traits are not
inherited like "beads on a string." Traits result from complex
(1) among the products of genes; (2) between genes and regulatory
expressed by other genes; (3) between genes and proteins, and
factors such as nutrients, temperature, etc.; (4) chance effects during
The allele encodes an enzyme which converts pigment precursors into
pigment; or a protein required for pigment deposition. (Humans;
The allele encodes a regulatory protein which represses synthesis or
of pigment. (Horse; foxglove)
inheritance can be seen to "work" is that in many cases we can hold all
the above factors constant, for a given genotype (genes
a trait) and a given
phenotype (appearance of trait).
can work (still at a SINGLE gene locus)
we can use molecular genetics to create artificial alleles in
animals and plants. There are two ways to make a transgene,
which have different consequences for inheritance:
dominance. Codominant alleles each contribute to the
for example A and B blood type alleles together produce AB blood
Incomplete dominance means that the hybrid produces a lesser degree of
the dominant phenotype than the purebreeding dominant.
If an allele (either dominant or recessive) results in death before
a class of progeny will be absent from the offspring. What ratios
allele (or pair of recessive alleles) at one gene locus can result in
diverse effects throughout the body.
Inject or transfect DNA into a fertilized egg. The DNA sequence
taken up somewhere in the genome, but not at the same position
any homologous gene. The position on the gene map is
(but fixed once the allele is inserted.)
A DNA sequence containing a linked selective marker (such as drug
is put into embryonic stem cell culture (ES cells). The ES cells
are put into a blastula, which develops into a chimeric offspring;
a pure-breeding line is bred. In this case, the new allele recombines
homologously and replaces an allele at a standard map position.
Problem. Explain how to breed transgenic mice to create a mouse
for sickle-cell anemia.
Pászty et al,
1997 October 31; 278: 876-878.
is caused by a single base pair defect in human beta-globin.
To test drug
for sickle disease, can we generate a transgenic mouse model for human
blood cells sickel under stress.
sickle only when attacked by malaria parasites. Prevents malaria.
to exhibit sickle-cell pathology, the native mouse genes--all at
loci--must be defective (null alleles.) We have a transgenic
human Hb-alpha, Hb-beta-sickle
on a transgene,Tg(Hu), inserted
in the mouse genome (not at the mouse globin genes.) But the
still has its own genes producingalpha
construct this strain,
the transgenic strain was intercrossed with a mouse strain heterozygous
for null alleles for alpha
would you need to cross?
mice would show the desired phenotype of blood with entirely human
have to do to create a similar model with exclusively normal human
Why would this be important in order to use the model? (For
interest, read Ryan et al, 1997.)
What is the
of sex? Why have so many animal and plant species evolved the
mechanisms of sexual recombination?
diverse combinations of traits, because when the environment
there is greater chance that some individuals will survive.
plants develop two different sexual types (sexes)? Different
species do it differently:
the latest about evolution of X and Y.
Male and female organs
on the same individual. (Garden pea plant; invertebrate worms)
Juvenile is born
female, later develops
into male; or vice versa. (Some fish and other vertebrates)
Diploid (female) versus
from unfertilized eggs (male) (Ants, bees, other social
Sex chromosomes--X, Y
W, Z (birds; moths). One member of pair (male Y, or female W)
is largely degenerate, having lost most of its genes through
that show X,
Y sex determination can have two different mechanisms of addressing gene
either case, traits encoded by genes on the X chromosome will show
inheritance. A female carrying two recessive X-linked alleles,
crossed with a wild-type male will produce criss-cross
inheritance. This is because the
Y chromosomes from the male all behave as null alleles
So the recessive allele from the female parent is always expressed in
male offspring. But her female offspring will receive one
allele from the father.
inactivation of one X or the other, in early embryonic cells.
down-regulation of gene expression from both X chromosomes. (Drosophila)
paired chromosomes are called autosomes.
X-linkage, you need to know the results of these crosses:
X X with X
X X with X
X X with X
X X with X
also need to FIGURE OUT THE PARENTS of a given combination of offspring.
particularly common because they only need one recessive allele present
for the phenotype to be expressed in the male. Some examples:
One of the
features of Fragile X syndrome is the role of imprinting
by methylated genes. (See next week.)
of all men
are partly color-blind.
Defective alleles are so common because (a) their effect is non-lethal,
and (b) the genes for red and green photoreceptors are extremely
and lie close together on the X chromosome, where they can recombine
over) with each other by mistake. Sometimes a color-blind person
can see a different "hybrid" color that no one else can!
Pedigrees, here ; SOLUTIONS;
Still more pedigrees **Medical Pedigrees
understand "dominant" and "recessive":
Dominant gene makes MUCH MORE than enough protein to cause a trait.So
one is needed; perhaps only in some cells.
Incompletely Dominant gene makes BARELY ENOUGH protein for the
So TWO COPIES are needed for the FULL trait.
Recessive gene makes no protein; inactive or partly active protein; or
not enough protein for the trait.
Penetrance and Variable Expressivity
real people, inheritance of any trait (dominant or recessive) is often
confounded by partial penetrance or by variable
of a trait.
percentage of individuals with a genotype who actually show the
If only 80% of people with the genotype actually develop the trait,
you could pass on a trait without showing it -- even if the trait is
is the degree of the trait. For example a genetic defect causing
mental retardation (such as Fragile X) can result in individuals with a
very wide range of intellect; and you cannot predict the degree of