Human Genetics Principles
in a Nutshell
by James L. Weber, Ph.D.
June 2005
Our bodies are comprised
of trillions of microscopic units called cells. Cells in turn are built
up from many specific types of molecules, both large and small. The large
molecules or macromolecules include polysaccharides, nucleic acids and
proteins.
Proteins are the workhorses
of our cells:
-
proteins are the building
blocks for most cellular and organismal structures;
-
proteins are the enzymes
which catalyze the chemical reactions which make life possible;
-
proteins control communications
between and within cells;
-
proteins control the expression
of genes;
-
proteins replicate the
genetic material.
There are about 30,000 different
types of proteins in our bodies. Each protein is present in many, many
copies. An adult, for example, carries about 1021 (a billion
trillion) hemoglobin molecules. Hemoglobin is the protein in our blood
which ferries oxygen from the lungs to the rest of our body.
The flow of genetic information is:
DNA to RNA to Protein.
Each protein is a linear
polymer of a specific sequence of 20 different amino acids. DNA is also
a linear polymer comprised of 4 types of nucleotides. The sequence of
amino acids in each protein is encoded by a segment of DNA called a gene.
Three consecutive nucleotides in a gene encode a single amino acid in
the corresponding protein. The genetic code is universal among all living
things.
Each human life begins with
a single, microscopic cell. This single cell contains no bones, liver,
brain, or any other adult tissue, but does contain a full complement of
genetic instructions (genes) to specify all these tissues. In this very
real sense, our genome is a blueprint for people. The genetic blueprint
encodes the sequences of all the proteins within our bodies and also programs
human development for all stages of our lives from the single cell to
old age.
DNA is a double helical
molecule with specific base pairing rules. Each of the two strands of
the double helical structure serves as a template for synthesis of a new
DNA strand during replication. Before a cell divides, the DNA within the
cell nucleus is copied with exceptional fidelity. Each of the two daughter
cells receives an identical copy of the DNA instructions.
The sum total of DNA within
an organism is the organism’s genome. The human haploid genome (one
copy of each chromosome) contains about 3 billion nucleotides. Each chromosome
contains a single very long DNA molecule. Each of the approximately 30,000
genes within our genome is located at a precise position along one of
the chromosomes.
The Human Genome Project
is the organized, international effort to map and sequence the entire
human genome. Much information about the human genome including maps and
sequences are available through the internet. The great majority of the
human DNA sequence has now been determined.
DNA is an exceptionally
ancient and stable molecule. It is passed from one generation to the next
with only very gradual change. The nucleotide sequences of chimpanzee
(our closest living relative) and human DNA are about 98.5% identical
despite the fact that our last common ancestor lived about 6 million years
ago. Similarities in DNA nucleotide sequences can be detected between
all free living organisms including reptiles and plants, worms and fungi,
and humans and bacteria. The degree of similarity in DNA nucleotide sequences
from two species indicates the evolutionary relatedness of the two species.
Humans have 46 total chromosomes,
two copies of each of 23 different types. Chromosomes 1 through 22 are
the same in both males and females. The sex (X and Y) chromosomes differ
between the sexes. Males have one X and one Y chromosome, whereas females
have two X and no Y chromosomes. One copy of each chromosome type is inherited
from the mother and one from the father. A father contributes an X chromosome
to each of his daughters and a Y chromosome to each of his sons.
Each pair of homologous
human chromosomes, whether from a single individual or from two individuals
are about 99.9% identical in sequence. This is why all humans from all
parts of the planet are so much alike, and so different from all other
animals including even our closest living relatives. Nevertheless, with
3 billion total nucleotides, 0.1% difference means about 3 million nucleotide
differences among homologous chromosomes. These DNA sequence differences
are largely, but not entirely, responsible for the differences among people.
Some human traits and diseases
are completely heritable, some partially heritable, and some are not influenced
by genes at all. Examples of traits and disorders in each category are
shown below. Traits and disorders are established to be heritable by family
studies, twin studies and animal studies. Not all human traits have been
examined for heritability. Traits and disorders which are partially heritable
are also influenced by nongenetic or environmental factors. As examples,
diet influences height, and cigarette smoking influences lung cancer.
Completely (or nearly completely)
heritable:
-
gender
-
eye color
-
skin color
-
cystic fibrosis
-
muscular dystrophy
-
deafness (many forms)
Partially heritable:
Not (or only very weakly) heritable:
Human diseases are inherited
through dominant, recessive and complex modes. Dominant inheritance means
one copy of the abnormal gene is sufficient to cause disease. Examples
of dominant disorders include Huntington’s disease, some forms of
breast cancer and some forms of Alzheimer’s disease. Recessive inheritance
means two abnormal copies of the relevant gene must be present in the
affected individual. Examples of recessive disorders include cystic fibrosis,
sickle cell anemia and many forms of deafness. When an abnormal gene responsible
for a recessive disorder is located on the X chromosome, then only males
are primarily affected. Examples of such "sex-linked" recessive
disorders are hemophilia and color blindness. Complex inheritance often
means that several genes combine to influence a single trait or disease
and that nongenetic factors also play a role.
Through the genome project
and through other studies, scientists are learning which nucleotide sequence
differences influence specific disorders and traits. Today, we know relatively
few of the genetic variations which affect common human traits and disorders.
However, many scientists are working on this problem, and our catalogue
of such variants is growing rapidly. Along with this knowledge has come
the technology necessary to efficiently screen for DNA variations. Using
a small of amount of blood or other tissue from a donor, laboratory experts
can now readily determine the nucleotide sequence of virtually any segment
of human DNA.
Our fantastic new ability
to screen human DNA sequences has the potential to provide great benefit
or great harm. Many tough ethical, legal, and social questions are raised
by our new genetic technologies. We will wrestle with these tough issues
all of our lives. The more people understand genetics, the better prepared
they will be to deal with these issues. Genetics education is therefore
critical to effectively applying this powerful new knowledge and technology.
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