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Cells
Figure 1.
An example of groups of cells working together in a specific
tissue type can be seen here. This is a photograph of
muscle cells, which combine their efforts in muscle tissue
to perform a common function: muscle contraction and relaxation.
The green lines represent the muscle cell membrane (called
the sarcolemma)and the bright purple-pink spots represent
the nuclei in the muscle cells. |
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Genes
Figure 2. |
We say that cells are the common
denominator of life and that genes are the smallest, common
units of inheritance. The genes contain long stretches
of the genetic code, which gets copied so that this genetic
code can be passed on to our children.
The genetic code is made up of four chemical bases that
are arranged in many different ways in different genes.
The chemical bases that make up the genes are represented
by the letters A, T, C, and G. The genes are found on
chromosomes in the cells of our body. Genes are important
because they contain the recipes for making proteins.
Therefore, researchers often say that "gene X
codes for protein X." |
Proteins
| Proteins are very important in our bodies
because they control the structure and most of the functions
that our bodies can perform. The role of a protein depends
on its shape and what other proteins and chemicals it
interacts with. Some proteins build muscle, while other
proteins help our blood to carry oxygen. There is a vast
array of functions that different proteins perform. In
addition, certain proteins may only be active and functioning
in certain kinds of cells in our body. A muscle protein,
for example, will not be expressed in a bone cell. Therefore,
we can say that most proteins are expressed in specific
cells at a specific point of ones lifetime and our genes
code for all of this complex information. |
Figure 3. |
Dystrophin Associated
Complex
Below
in figure 4, a very important group of proteins affiliated
with the muscle cell are shown. This group of proteins is called
the Dystrophin Associated Protein Complex, or DAPC. Each protein
that is named in the diagram is coded for by a different gene,
and the different genes are found on different chromosomes.
For example, the dystrophin gene is found on the X chromosome
and codes for the dystrophin protein. An error in the dystrophin
gene and therefore in the dystrophin protein leads to Duchenne
or Becker muscular dystrophy. The gamma-sarcoglycan gene, located
on chromosome 13, codes for the gamma sarcoglycan protein, and
an error in the gene and protein may lead to a form of limb-girdle
muscular dystrophy. Thus, errors in any of the genes that code
for proteins associated with the DAPC may lead to a form of
muscular dystrophy or a myopathy. If a person has an error in
such a gene, which lies on a certain chromosome, and this chromosome
is passed on to the person's child, a hereditary muscle disease
may be present in the family.
Figure 4. The black line in the
middle of this figure that is made up of circles represents
the muscle cell membrane. The part of the figure below
the membrane is the inside of the cell, while the part
of the figure outside the membrane is the outside of the
cell. Some muscle proteins are located right at the cell
membrane, while others are located inside the cell. |
Chromosomes
The genes lie along structures called chromosomes. Our chromosomes
are tightly coiled, threadlike bundles of DNA s within cells
that are visible with a microscope. Segments of DNA are broken
down to form the genes. It is helpful to think of a string of
pearls as the chromosome, with each bead representing one gene.
It is estimated that every cell in a person's body contains
30,000 to 40,000 thousand genes that function to make us viable
human beings.
Normally, every cell in the human body
contains 46 chromosomes, or 23 pair of chromosomes. Each
chromosome has a copy of a form of a particular gene,
with a corresponding form of the same gene on the other
chromosome. The gene on one chromosome is inherited from
the father, and the corresponding gene on the partner
chromosome is inherited from the mother. Therefore, there
is a total of two copies of each and every gene. For example,
the “hair color” gene may lie on chromosome
5. One chromosome 5 may have a gene that codes for red
hair. The other chromosome 5 may have a gene that codes
for blonde hair. The result of these two genes may be
an individual with strawberry-blonde hair.
The picture in Figure 5 is called a karyotype.
Chromosomes are numbered according to their size, beginning
with the largest, chromosome 1. This is a female karyotype
because the 23rd pair of chromosomes contains two X chromosomes.
A male has one X and one Y chromosome. |
Figure 5. |
Mutations
Mutations can occur in our DNA. We can think of DNA as a tightly
twisted ladder made up of letters (the genetic code, A,T,C,G)
that form sentences (genes). These sentences give our bodies
instructions on how to build proteins. If one of the letters
or words in the sentence is incorrect, the sentence may no longer
make sense, and therefore our bodies won't know what to do with
that particular set of instructions. Consequently, a protein
may be made incorrectly, or may not be made at all. Therefore,
genetic mutations result in abnormal, shortened, or nonexistent
proteins.
Genetic mutations can occur in two main ways:
Mutations can be inherited, or passed to a child from his mother
or father.
Mutations can occur sporadically (by chance) in the DNA of an
embryo.
Further, mutations can be inherited in different patterns.
• Autosomal Dominant
• Autosomal Recessive
• X-Linked
Autosomal
Dominant
Autosomal dominant means that an individual needs to inherit
only one copy of a gene with a mutation from either the mother
or the father in order to develop a genetic disease. In autosomal
dominant inheritance, we typically see several generations of
affected individuals, both males and females will be affected
in approximately equal proportions, and both a male and a female
can pass on the mutation to a daughter or a son. (DIAGRAM
of Pedigree and little people) This means that with each
pregnancy, there is a 50% chance (or a 1 in 2 chance)that the
baby will inherit the mutation for a given disorder.
For example, if A represents the healthy gene and a represents
the gene with the genetic alteration, statistically, we would
expect the following proportions of children to be affected
or not affected with the given autosomal dominant disease.
The purple letters in Figure
6 represent the parent’s genes, and the black letters represent
the genes of the potential offspring.
Figure 6.
As you can see, 50% of the children would inherit AA, and
be healthy, while the other 50% would inherit Aa and have
the given autosomal dominant disease.
Autosomal Recessive
Autosomal recessive inheritance is different from autosomal
dominant inheritance in that an individuals needs to inherit
two copies of a mutation in a gene, one from the mother and
one from the father, in order to be affected with a genetic
disorder. An example of an autosomal recessive disease is limb-girdle
muscular dystrophy, a disease that causes weakness in the limbs
and pelvic girdle of affected individuals. Limb-girdle muscular
dystrophy (LGMD) is a group of diseases, a few of which are
inherited in an autosomal dominant pattern. However, most forms
of this disorder are autosomal recessive and therefore, an individual
must inherit a mutation in the specific LGMD-causing gene from
both his or her mother and his or her father to develop LGMD.
With autosomal recessive inheritance, the parents of an affected
child are called carriers. This means that they carry a mutation
in a given gene, but this mutation does not affect the person
clinically, and usually, the person doesn't know that he or
she carries the gene. To have an affected child, two carriers
would have to mate. Therefore, there would be a 25% risk with
each pregnancy that the baby would be affected with the autosomal
recessive disorder. We get this risk estimate by the fact that
each parent can pass on either a chromosome with a "healthy
gene" or their chromosome with the genetic mutation. 1/2
x 1/2 = 1/4 or 25%. In autosomal recessive inheritance, we may
see that there is no other affected member in the family. However,
both males and females are equally likely to pass on the gene
with the mutation and both males and females can inherit the
mutation.
For example, if A represents the healthy gene and a represents
the gene with the genetic alteration, statistically, we would
expect the following proportions of children to be affected
or not affected with the given autosomal recessive disease.
The purple letters represent
the parent’s genes, and the black letters represent the
genes of the potential offspring.
Figure 7.
As you can see in Figure 6, 50% of the children would inherit
Aa, and be healthy, but would be carriers of the genes with
the mutations. 25% would be AA and would have two healthy
genes, while the remaining 25% would inherit aa and have the
given autosomal recessive disease.
X-Linked
X-linked genetic diseases are a little more complicated to explain.
There are two types of X-linked diseases: recessive and dominant.
To begin with, it is important to remember that females have
two X chromosomes. One can be thought of as a "back up"
copy. Males have only one X chromosome. Therefore, if a disease
is X-linked recessive, a female who has one copy of the altered
gene on one of her X chromosomes will not have the disease,
but will be a carrier of the disease. The male, however, who
has only one X, will have the disease. An affected male can
then pass on this genetic mutation to his daughters, who will
be carriers, but not to his sons (since he would pass on a
Y to his sons). A female carrier has a 50% chance to pass
on the altered gene and have a daughter who is a carrier,
and a 50% chance to pass on the altered gene to a son, thus
having an affected son. There is also a 50% chance that her
son would be healthy and not carry the genetic mutation.
X-linked dominant diseases are much more rare than X-linked
recessive diseases. In X-linked dominant diseases, an individual
needs only to have one copy of the altered gene on the X chromosome
to have the genetic disease. Thus a female can be affected
even though she has the "back up" X chromosome,
and there is a 50% chance that the genetic alteration will
be passed on in each pregnancy and a 50% chance that the baby
will be affected with the genetic disease. Every daughter
that an affected father has will have the X-linked dominant
disease, while every son the affected father has will not
be affected (because the son will inherit the Y chromosome
from his father).
Sporadic Mutations
Another way for an individual to develop a genetic disease is
for a genetic mutation to occur by chance. This is what geneticists
call a sporadic mutation. For example, using Duchenne muscular
dystrophy (DMD), it is possible that a mother may carry a mutation
in the gene that leads to DMD. The mother is very unlikely to
be affected with DMD because she has a second X chromosome that
compensates for the error in her other X chromosome. However,
since males only have one X chromosome, they do not have a back
up chromosome to compensate for such an error. Therefore, If
a mother did carry an altered DMD gene, there would be a 50%
chance that she would pass on the gene to each child. If one
of her children was a female, there would be a 50% chance that
the female baby would carry (and be unaffected) the altered
gene, and a 50% chance that she would have inherited the unaltered,
healthy gene. If this carrier mother had a son, there would
be a 50% chance the son would carry the altered X chromosome
and thus be affected, and a 50% chance that he didn't inherit
the altered copy and would be healthy. However, in some cases,
we know that a mother of an affected child does not carry an
altered gene. In this case, we have learned that a random change
in DNA can sometimes occur in a critical region of DNA, including
a gene region that codes for an important protein. Sometime
after the sperm fertilized the egg, an error occurred simply
by chance in the new baby's DNA in the specific DMD gene. As
a consequence, the baby has an altered DMD gene. New dominant
and X-linked mutations are more likely to occur than autosomal
recessive sporadic mutations, although a sporadic genetic alteration,
in general, is a rare event.
It is important to understand that all people have occasional
errors in their genes and DNA. In most cases, because we have
a pair of genes, if one contains an error, the other can compensate
and the person will have no medical problems. This is true for
autosomal recessive conditions. In autosomal dominant and X-linked
conditions, one error may be enough to cause illness, but this
happens very rarely. Many of the changes produced because of
mutations in genes are so mild that they go unnoticed. Also,
our bodies have built-in DNA proofreading mechanisms that are
capable of fixing many kinds of mutations in our DNA before
the mutations cause problems. Importantly, one should never
feel ashamed or guilty for having a child with a genetic condition.
Such instances are left up to chance and are no ones fault.
Scientific research has shown that about 3% of all children
are born with some recognizable birth defect and probably all
of us would be found to have some abnormal gene if we looked
hard enough at our DNA.
Family Trees
In order to determine what type of inheritance pattern a particular
genetic disorder follows, doctors and genetic counselors often
construct a family tree. The scientific term for a family tree
is a pedigree. Examples of pedigrees are shown above. A circle
is used to represent a female and a square represents a male.
A line going diagonally through the shape means the person has
died. Healthcare professionals use different shading patterns
to designate different medical conditions that a family member
has. The shading patterns and their definitions can be found
in the key that accompanies a pedigree.
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To construct a pedigree, healthcare providers ask many
types of questions, often about three generations of
your family, including:
•Your ethnic background(s)
•How many siblings/aunts/uncles/cousins you have
•Ages of relatives
•Medical information on your family members, dating
back 3 generations
•Is any one in the family related to each other
by blood?
•Did any babies in the family have birth defects
or medical problems
•Did any one in the family have miscarriages?
•A detailed medical history on the patient will
be taken.
Figure 8: This family tree displays
an autosomal dominant genetic disorder. We can determine
this because there are several generations affected,
both females and males are affected in equal proportions,
and multiple family members have the disorder.
|
Figure 8. |
All these questions help doctors and genetic counselors
to determine whether a genetic disease could have been inherited
from a particular side of the family and who else in the family
may be at risk for the same genetic disorder. Below are links
to some web sites that may be helpful in further explaining
some genetic concepts:
Links
Basic
Genetics
Biology
Online
Dr.
Chromo's School |
