Video Transcript
The pedigree chart provided shows
the inheritance of Duchenne muscular dystrophy, DMD, within a family. Couple A and B decide to have
another child. What is the probability, in
percent, this child will be a female carrier of DMD?
This question is asking about the
inheritance of a genetic disorder, so let’s begin by reviewing some key facts about
genetics and inheritance.
Humans have 23 pairs of
chromosomes. One of each pair comes from the
biological mother and the other from the biological father. 22 pairs are called autosomes. And they are homologous chromosomes, which means that they are of a similar
length. And they have the same genes at
each location along the chromosome.
Remember, the alleles, the
different varieties of a gene, in a homologous pair are not necessarily going to be
the same, as they have come from two different people who are genetically
different. For example, chromosome 15 carries
the gene for eye color. However, you may get a brown allele
from your father and a blue allele from your mother, as shown in this example.
Here, the resulting genotype is
heterozygous, hetero- meaning different and -zygous refers to the state of the
alleles, so this means one of each type of allele. The dominant allele will be
expressed in the phenotype, the observable outcome. In eye color, brown is dominant
over blue, so the phenotype here will be brown eyes.
Let’s look at a normal Punnett
square to look at the potential outcome of a genetic cross. The alleles at the top are the ones
we inherit from our mother, and the alleles on the left are the ones we inherit from
our father. Each intersecting box is a
potential allelic combination of an offspring.
The pink box in the top left has
two dominant alleles, making the genotype homozygous dominant, homo- meaning same,
so the same dominant alleles. And the phenotype is dominant
too. The two yellow boxes both have a
dominant and a recessive allele, so the genotype is heterozygous and the phenotype
is dominant. And lastly, the green box in the
lower right has two recessive alleles, so the genotype is homozygous recessive and
the phenotype is recessive.
In this example, 75 percent of the
offspring will have a dominant phenotype, and 25 percent will have a recessive
phenotype.
We have so far talked about the 22
pairs of autosomes, but what about the 23rd pair? Well, the chromosomes of this last
pair are the sex chromosomes and can either be X or Y. Females have two X chromosomes, and
males have an X and a Y. The X chromosome is much larger, as
you can see, and carries about 900 genes, whereas the smaller Y chromosome only
carries about 55 genes. The majority of the genes carried
on the X and Y chromosomes are different. This creates interesting
inheritance patterns, as we will now see.
If the gene is only carried on the
Y chromosome, it means that only those with the XY chromosome pairing will express
them. For example, the gene controlling
the development of the male reproductive system is only found on the Y chromosome,
so only a person with the Y chromosome can develop this anatomy.
The recessive alleles for color
blindness and hemophilia are only carried on the X chromosome. So, if someone who is XY inherits
the hemophilia allele on their X chromosome, then they will have hemophilia. They are often referred to in a
question such as ours as an affected male. If someone who is XX inherits a
hemophilia allele, then they will only express it if their other X chromosome is
also carrying it and can be referred to as an affected female. If they end up with one dominant
allele and one recessive hemophilia allele, they are known as carrier females as
they can pass it on to their offspring, but they will not have hemophilia
themselves. This is why a higher proportion of
males have hemophilia than females.
These traits of genes that are
carried only on the sex chromosomes and are not affected by sex hormones are called
sex-linked traits. So, hemophilia is an X-linked
trait, and the development of male reproductive organs is a Y-linked trait.
Now, let’s look at the pedigree
chart from the question. It details how Duchenne muscular
dystrophy is inherited throughout a family. Notice that some of the individuals
are labeled as carriers, but there are no male carriers. This indicates that it is an
X-linked genetic disorder.
When you look at the top of the
pedigree chart, you can see that a carrier female and an unaffected male have
produced a male affected offspring. This confirms it is X-linked, as if
the gene was carried on an autosome, B could only have received a dominant allele
from their father and therefore would not be affected.
The cross we are looking at between
person A and person B has an unaffected female and an affected male. So let’s now work through this.
Here is the Punnett square for that
cross. We can see some differences from
the typical Punnett square we looked at before. Since Duchenne muscular dystrophy
is an X-linked trait, we are looking at the sex chromosomes specifically. Having female carriers in the
pedigree chart indicates that the allele for the disorder must be recessive.
Note, the not-affected dominant
allele is represented by a capital N and the recessive allele for the disorder by a
lowercase n. If the allele for Duchenne muscular
dystrophy is recessive, then the X chromosome of the affected male must carry this
recessive allele, while both X chromosomes of the unaffected female must have
dominant alleles.
As you may remember, when looking
at inheriting sex chromosomes, half of the offspring will be female, XX, as
illustrated in the top two boxes, and half will be males, XY, seen in the bottom two
boxes. The females have received the
dominant allele from the mother and the recessive one from their father. So they are heterozygous, which
means they are carriers. Since the males only have one X
chromosome, they will only have one copy of the allele. In this case, the only copy they
can have is the dominant one from their mother. Therefore, they will not express
the disease and are unaffected males.
The question was asking us what the
probability is that the child will be a female carrier of Duchenne muscular
dystrophy. We can now see that the
probability, in percent, that this child will be a female carrier of DMD is 50
percent.
