A THOUGHTFUL CONCEPTION
Genetic Expressions
A person’s appearance, personality and skills intrigue us. For many years, people tried to
understand the inheritance of complex traits; often making statements that “those folks are all
dark-complexioned” or “his big ears are a throwback to Uncle Joe.” Although a complex trait
may have genetic components, it also may have environmental components; separating these
components that act to produce a complex trait may be impossible. For this reason, we look at
simpler circumstances to gain perspectives on the bigger picture.
It is important to separate manifestation of a gene from the gene itself. Redness is a
genetic trait of blood, but a gene for red blood does not exist. Blood is red because of
hemoglobin, which is red and is a protein made in blood cells with active genes for hemoglobin.
Phenotype is the name given to the manifestation or expression of a gene. Genotype is the name
given to the presence of a gene in a person. We will see that a person may have a gene for a
trait, but not show the trait.
GENES STAND UP. Humans have understood for many centuries that “features” are
passed from generation to generation in plants and animals. The first modern insights to genetic
mechanisms came from Gregor Mendel nearly 150 years ago. His experiments laid the
foundation for principles called Mendelian genetics. An example of a Mendelian trait controlled
by a single gene is sickle cell anemia, which we have mentioned previously. Most people have
hemoglobin A, whereas people with sickle cell anemia have hemoglobin S. This gene is located
on chromosome 11 and, since we have two copies of chromosome 11, we have two copies of the
gene. Variant forms of a gene are called alleles. So a person could have two hemoglobin A
alleles, two S alleles, or A and S alleles. The allele for hemoglobin A is dominant to hemoglobin
S, which is recessive. Since the phenotypic expression of a dominant allele masks the expression
of a recessive allele, just one dose of the A allele produces hemoglobin A. In order to observe
the expression of hemoglobin S in an individual in the form of sickle cell disease, the person
must carry two copies of the S allele. People with one copy of each allele (A and S) are said to
be heterozygous, or carriers, because they have a risk of producing a child with sickle cell
disease. A person with two identical alleles (AA or SS) is said to be homozygous. An example
of a family tree (pedigree) demonstrating the inheritance of sickle cell anemia is shown in Fig.
11.
Standard Pedigree Symbols
Figure 10
Pedigree of Sickle Cell Anemia
Figure 11
The father and mother are both carriers of sickle cell anemia gene (sickle cell trait) because they each have one
(p.
20)of the S allele. However, neither parent has sickle cell disease. As the chromosomes separate in meiosis,
copy
When
the chance
for homozygosity
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will berelatives
passed on procreate,
from each parent
to each child.
On average, weof
expect
¼ of thedisorders
children to be
AA (normal hemoglobin), ½ to be AS (carrier) and ¼ to be SS (sickle cell anemia). Carriers may wish to
seek genetic counseling.
When close relatives procreate, the chance for homozygosity of recessive disorders
increases. Sex between close relatives is taboo in most cultures. It occurs through incest or in
communities isolated because of geographical, religious or social reasons. It can also occur
when two people are unaware that they are half- siblings or first cousins. Such matings increase
the likelihood that the two parents are heterozygous for one or more alleles that will then become
homozygous in the offspring. Homozygote recessive traits can be phenotypically expressed.
The concept of dominant and recessive traits is at the heart of Mendelian genetics. Some
human traits that have Mendelian inheritance patterns are listed in the following Table. The
Table provides only the phenotype; the genetic change underlying most of these phenotypes is
unknown, but inheritance patterns can still be predicted.
Phenotypic Traits
Dominant
Freckles
Dimples in cheeks
Polydactyl (extra toes or fingers)
Pigmented skin
Widow’s peak
Male pattern baldness
Tongue rolling
Free (unattached) earlobes
Farsightedness
Hemoglobin A
High blood cholesterol
Absence of cystic fibrosis
Absence of Tay Sachs
Huntington’s disease
Recessive
Absence of freckles
Absence of dimples
Normal number of digits
Albinism
Straight hairline
Full hair
Inability to roll tongue into a U shape
Attached earlobes
Normal vision
Hemoglobin S
Normal blood cholesterol
Cystic fibrosis
Tay Sachs
Absence of Huntington’s disease
Mendelian concepts have helped people to understand genetic inheritance. In reality,
genetic inheritance is more complex than simple dominance and recessiveness. For example,
there usually are many alleles for one gene. Some of these alleles may be dominant; other,
recessive. One allele may show different types of dominance in relation to another allele: codominant, overdominant, incompletely dominant, or recessive.
CREATING NEW ALLELES. Variety is an important survival factor in biology.
Variation in a new generation is introduced, as we have seen, through meiosis and fertilization.
Another means of introducing variation is through genetic mutation.
Genetic mutation creates a new allele from a gene. As we have seen, a mutation of only
one codon can convert hemoglobin A to hemoglobin S. Beta globin of hemoglobin S differs
from beta globin of hemoglobin A in only one amino acid out of 146.
A mutation may occur spontaneously without apparent cause. Alternatively, a mutation
may be caused by environmental chemicals, physical factors such as radioactivity or ultraviolet
light, or even biological agents such as a virus. A new mutation may be advantageous, neutral,
or harmful. Most mutations are harmful. Perhaps this accounts for the many mechanisms a cell
has to prevent and/or repair mutations. Cells have a way to neutralize some mutational events,
but these are only partially effective. Once a mutation has occurred, the cell may be able to
remove the mutated part of DNA and replace it with the original version.
Some genes have a higher frequency of mutation than others; they are less stable. The
reasons for this are largely unknown. Similarly, a mutation (such as the change from
hemoglobin A to hemoglobin S) can occur many times. Mutations may produce dominant or
recessive alleles. A new allele that lacks function will typically be recessive whereas a new allele
that creates a new function for a protein will typically be dominant. These are simply
generalized observations; many exceptions exist.
Mutations may occur in any cell, somatic or germinal. They may even occur in
mitochondrial genes. When a mutation occurs in a somatic cell capable of dividing, the change
will be passed on to all daughter cells. In this way mutations accumulate in a person’s body; the
likelihood of a person having cells with mutations increases with age. Many cancers are caused
by mutations. Older cells may be missing entire chromosomes. Mutations occurring in germ
cells can be passed on to future generations. Fortunately, the people who are most likely to be
reproducing are younger people, who are less likely to have mutations when compared with
older people.
Mutations can adversely affect reproduction. The effect may be slight impairment to
fertility or complete prevention of reproduction, i.e., sterility. It may be dominant or recessive.
It may affect both sexes or only one sex.
A majority of genes are capable of mutating to a lethal allele. Lethal mutations have the
phenotypic effect of death. Dominant lethals are self- limiting, eradicated with the death of the
cells or host. Recessive lethals in germ cells are passed on to many generations of offspring
through heterozygosity. Every person has about five to eight harmful recessives, phenotypically
expressed only when they become homozygous.
BEYOND MENDEL. Mendel’s principles explain single gene traits. Other traits such as
height, skin color, blood pressure, intelligence and personality at first seemed to be inherited in
different ways. Early in the 20th century it occurred to Ronald Fisher that complex traits may be
affected by a large number of genes and even environmental factors; in a word, they are multifactorial. This combination of genetic and environmental factors account for a range of
phenotypes such as range of heights in adult American men: 3 feet (91 cm) to 7 feet (213 cm).
There is a continuous distribution of phenotypes throughout the range, with very few individuals
at either extreme and with the majority of individuals concentrated in between. A graph of the
distribution forms a classical bell-shaped curve (See Fig. 12).
Interactio n of genes and environment
to produce a phenotypic trait is clear. Genes
and environment interact to produce skin
color. The color of a person with genes for
melanin darkens with sun exposure. Another
example is body size. A person may have
genes that could result in a large body, but
proper nutrition during childhood is necessary
Bell Curve
for those genes to fulfill their potential; proper
Figure 12
nutrition delayed until adulthood is too late for
body-size genes to be effective.
Diseases also have genetic plus environmental components. Notable are hardening of
arteries, diabetes and cancer. The interaction of genes and environment is obvious in heart
attacks. A major cause of heart attacks is blockage of the coronary arteries that feed heart
muscle. The blockage may be caused by cholesterol, blood clots, or by both. Genes are
responsible for cholesterol in the blood. Other genes are responsible for blood-clotting proteins.
Beyond these genes are numerous others affecting blood flow in arteries. Environmental factors
(lifestyle, in this example) affecting heart health include diet, exercise, smoking and stress.
Intelligence and behavior are complex traits affected by both genetics and environment.
Indeed, the terms intelligence and behavior are each used to denote a variety of attributes. For
example, there are many different ideas about the nature of intelligence, the general ability to
reason and solve various kinds of problems. Testing to measure the intelligence of people in
large groups demonstrates a bell- shaped distribution curve.
Some of the best research on genetic factors influencing behavior and intelligence has
been done by comparing identical (monozygotic) twins who have grown up together with those
who were reared separately in families at great distance. Regardless of whether the identical
twins were reared together or apart, their measured intelligence in most cases is very much the
same. This is in contrast to non-identical, fraternal (dizygotic) twins who can have widely
varying intelligence even when reared together and especially when reared apart.
Production of brain chemicals related to behavior – dopamine, norepinephrine and
serontonin – is influenced by genes. An excess or deficiency of these chemicals can adversely
affect behavior. Some mental diseases can be caused by single genes. Phenylketonuria (PKU),
Lesch-Nyhan syndrome and Tay Sachs disease are examples of single-gene disorders that cause
mental retardation. Other mental disorders are multifactorial, such as alcoholism, schizophrenia
and bipolar (manic-depressive) disorder.