“HBB” Genetics Home Reference, National Institute of
Medicine
Reviewed: July 2009
Published: January 13, 2014
Sickle cell anemia, a common form of sickle cell
disease, is caused by a particular mutation in the HBB
gene. This mutation results in the production of an
abnormal version of beta-globin called hemoglobin S or
HbS. In this condition, hemoglobin S replaces both betaglobin subunits in hemoglobin. The mutation changes a
single protein building block (amino acid) in betaglobin. Specifically, the amino acid glutamic acid is
replaced with the amino acid valine at position 6 in betaglobin, written as Glu6Val or E6V. Replacing glutamic
acid with valine causes the abnormal HbS subunits to
stick together and form long, rigid molecules. The rigid
HbS molecules bend red blood cells into a sickle
(crescent) shape. The sickle-shaped cells die
prematurely, which can lead to a shortage of red blood
cells (anemia). The sickle-shaped cells can also block
small blood vessels, causing pain and organ damage.
Germinal and Somatic Mutations
by Phillip McClean – North Dakota State University
Eukaryotic organisms have two primary cell types --germ and somatic. Mutations can occur in either cell
type. If a gene is altered in a germ cell, the mutation is
termed a germinal mutation. Because germ cells produce
gametes, some gametes will carry the mutation and it
will be passed on to the next generation when the
individual mates. Typically germinal mutations are not
seen in the individual containing the mutation.
Somatic cells make up all the cells in the body other than
the germ cells. Mutations in somatic cells are called
somatic mutations. Because they do not occur in cells
that give rise to gametes, the mutation is not passed
along to the next generation by sexual means. To
maintain this mutation, the individual containing the
mutation must be cloned. Two examples of somatic
clones are navel oranges and red delicious apples.
Horticulturists first observed the mutants. They then
grafted mutant branches onto the stocks of "normal"
trees. After the graft was established, cuttings from that
original graft were grafted onto tree stocks. In this way
the mutation was maintained and proliferated.
Most tissues are derived from a cell or a few progenitor
cells. If a mutation occurs in one of the progenitor cells,
all of its daughter cells will also express the mutation.
For this reason, somatic mutations generally appear only
in one part of the body.
Cancer tumors are a unique class of somatic mutations.
The tumor arises when a gene involved in cell division, a
protooncogene, is mutated. All of the daughter cells
contain this mutation. The phenotype of all cells
containing the mutation is uncontrolled cell division.
This results in a tumor that is a collection of cells called
tumor cells.
Mutations and Disease
The Tech Museum of Innovation
A mutation is an accidental changes in its code.
Mutations can lead a protein being missing or in the
wrong shape, and that can lead to disease.
We all start out our lives with some mutations. These
mutations inherited from your parents are called germline mutations. However, you can also acquire mutations
during your lifetime. Some mutations happen during cell
division, when DNA gets duplicated. Still other
mutations are caused when DNA gets damaged by
environmental factors, including UV radiation,
chemicals, and viruses.
Few mutations are bad for you. In fact, some mutations
can be beneficial. Over time, genetic mutations create
genetic diversity, which keeps populations healthy.
Many mutations have no effect at all. These are called
silent mutations.
But the mutations we hear about most often are the ones
that cause disease. Some well-known inherited genetic
disorders include cystic fibrosis, sickle cell anemia, TaySachs disease, phenylketonuria and color-blindness,
among many others. All of these disorders are caused by
the mutation of a single gene.
Most inherited genetic diseases are recessive, which
means that a person must inherit two copies of the
mutated gene to inherit a disorder. This is one reason
that marriage between close relatives is discouraged; two
genetically similar adults are more likely to give a child
two copies of a defective gene.
Diseases caused by just one copy of a defective gene,
such as Huntington's disease, are rare. Thanks to natural
selection, these dominant genetic diseases tend to get
weeded out of populations over time, because afflicted
carriers are more likely to die before having children.
Scientists estimate that every one of us has between 5
and 10 potentially deadly mutations in our genes-the
good news is that because there's usually only one copy
of the bad gene, these diseases don't manifest.
Cancer usually results from a series of mutations within
a single cell. Often, a faulty, damaged, or missing p53
gene is to blame. The p53 gene makes a protein that
stops mutated cells from dividing. Without this protein,
cells divide unchecked and become tumors.
Sickle cell anemia is the result of a point mutation, a
change in just one nucleotide in the gene for
hemoglobin, protein in red blood cells that transport
oxygen in our bodies. This mutation causes the
hemoglobin in red blood cells to distort to a sickle shape
when oxygen leaves the cell. The sickle-shaped blood
cells clog in the capillaries, very small veins, cutting off
circulation.
Having two copies of the mutated genes cause sickle cell
anemia, but having just one copy does not, and can
actually protect against malaria - an example of how
mutations are sometimes beneficial.