|Genetics I - Normal Background
inheritance; heterozygous; inheritance patterns; heredity
and disease; heritable; genetic markers
is common knowledge that a person's appearance (e.g., height, hair color, skin color, eye color, etc) are determined by genes.
A person's mental abilities and natural talents are certainly affected by heredity. Some diseases (or susceptibility to acquire
a disease) are also known to be genetically related.
An inherited abnormal trait or anomaly may be of no real consequence
to a person's health or well being (for example, a white splotch of hair or an extended ear lobe). An inherited anomaly may
be of minor consequence
(for example, color blindness).
On the other hand, an inherited disorder may
also have multiple effects resulting in
dramatically decreased quality or length of life. For some genetic disoders, genetic counseling and prenatal diagnosis may
The terms anomaly, abnormality, disorder, defect, disease, and syndrome are not used consistently and do
not have precise definitions.
Human beings have cells with 46 chromo-somes (2 sex chromosomes and 22 pairs of autosomal,
that is, non-sex chromosomes). Males are 44,XY; females are 44,XX.
Each chromosome is comprised of 2 extremely long
DNA molecules in combination with chromosomal proteins. Genes are defined by intervals along one of the DNA molecules.
location of the gene is called the locus. Most genes carry information which is necessary to synthesize a protein. The pairs
of autosomal chromosomes (one from mom and one from dad) carry basically the same
information; that is, each has the same
genes, but there may be slight variations in the DNA sequence of nucleotide bases in each gene.
Alleles are different
variants of a particular gene.
The information contained in the nucleotide sequence of a gene is transcribed to mRNA
(messenger RNA) by enzymes in the cell's nucleus and then translated to a protein in the cytoplasm. This protein may be a
structural constituent of a given tissue. It may be an enzyme which catalyzes a chemical reaction, or it may be a hormone.
There are also many other potential functions for proteins.
Recessive disease gene
a gene is abnormal, it may code for an abnormal protein or for an insufficient
amount of a normal protein. Since the autosomal
chromosomes are paired, there
are 2 copies of each gene. If one of these genes is defective, the other may code for sufficient
protein so that the abnormality is not clinically apparent. This is called a recessive disease gene.
If one abnormal
gene somehow produces disease, this is called a dominant heredi-
tary disorder. In the case of a dominant disorder, if one abnormal gene is inherited from
mom or dad, the child will show the disease. In the case of a recessive disease, if one abnormal gene is inherited, the child
will not show clinical disease, but they will pass the abnormal gene to 50% (on average) of their
A person with one abnormal gene is termed
HETEROZYGOUS for that gene. If a child receives an abnormal recessive disease gene from both parents, the child will show
the disease and will be HOMOZYGOUS for that gene. If two parents are each heterozygous for a particular recessive disease
gene, then 25% of their children (on average) will be homozygous for that gene and show the disease. If one parent is homozygous
and the other heterozygous, then 50% of the children
will be homozygous.
Genetics II - Disorders: autosomal and X-linked
Almost all diseases
have a genetic component, but the importance of that component varies. Disorders where genetics play an important role, so-called
genetic diseases, can be classified as single gene defects, chromosomal disorders, or multifactorial.
defects are also called mendelian disorders.
A single gene disorder is one that is determined by a
specific allele at a single locus on one or both members of a chromosome pair. Single gene defects are rare, with a frequency
of less than 1 in 500 births, but since
there are about 3000 known their combined impact is significant. The incidence
of serious single gene disorders is estimated to be about
1 in 300 births.
Single-gene disorders are characterized
by the pattern of transmission in families; this is called a pedigree. A kindred includes the relatives outside of the immediate
family. The affected individual that initially comes to
light or is of immediate interest is called the proband. The brothers
and sisters of the proband are called sibs.
There are only four basic patterns of single gene inheritance:
The observed effect of an abnormal gene (the appearance of a disorder)
is called the abnormal phenotype. A phenotype expressed in the same way (in both homozygotes and heterozygotes) is dominant.
A phenotype expressed only in homozygotes (or, for X-linked traits expressed in males but not females) is recessive.
for a recessive gene are called carriers. They usually don't express the phenotype clinically, but it can frequently be identified
by sensitive laboratory methods.
(Autosomal Dominant - like in HD and Familia Hypercholesterolemia)
(Autosomal Recessive - Cystic Fibrosis, PKU, AAT, Sickle Cell, ADA)
In autosomal dominant inheritance, the abnormality
or abnormalities appear in every generation. Every affected child has an affected parent and, on average, each child of an
affected parent has a 50% chance of showing the disease. Normal members of the family do not transmit the disease. Males and
females are equally likely to have the disease and to transmit the disease. Male-to-male transmission can occur (unlike with
X-linked dominant inheritance) and males can have unaffected daughters (unlike with X-linked dominant inheritance).
autosomal recessive inheritance, the parents of an affected individual may not express the disease. On average, the chance
of an affected child's brothers or sisters having the disease are 1 in 4.
Males and females are equally likely to be
affected. For a child to have symptoms of an autosomal recessive disorder, the child must receive the recessive gene from
BOTH parents. Because these disorders are rare, when a child has symptoms of an autosomal disorder there is a chance that
the parents are related.
X-Linked Inheritance (Hemophilia A, Tay-Sachs, Duchenne Muscular Dystrophy)
X-linked recessive inheritance, the incidence of the disease is much higher in males than females. Since the abnormal gene
is carried on the X chromosome, males do not transmit it to their sons; they do transmit it to all their daughters.
presence of one normal X chromosome masks the effects of the X chromosome
with the abnormal gene so almost all of the daughters
of an affected man appear normal, but they are all carriers of the abnormal gene. The sons of these daughters then have a
50% chance of receiving the defective gene.
In X-linked dominant inheritance, the presence of the defective gene makes
manifest in females even if there is also a normal X chromosome present. Since males
pass the Y chromosome to
their sons, affected males will not have affected sons, but all of their daughters will be affected. Sons or daughters of
affected females will have a 50% chance of getting the disease (except for the rare case of the female with two abnormal.
Only a few, very rare, disorders are classified as
X-linked dominants. One of these is hypophosphatemic rickets (also called vitamin D resistant rickets).
Genetics III - Disorder Types
In chromosomal disorders, the defect is due not
to a single gene, but to an excess or deficiency of the genes contained in a whole chromosome or chromosome segment.
syndrome is the most common chromosomal disorder (1 out of 800). Other common examples are Klinefelters syndrome (1 out of
1000 males) and Turners syndrome (1 out of 5000 females).
Genetics III - Disorder Types continued
of the most common diseases which affect humans undoubtedly involve inter-actions of numerous genes, e.g., coronary heart
disease, hypertension, stroke, and various kinds of cancer.
are small organelles present in most of the body's cells which function in the conversion of certain chemicals in our food,
in the presence of oxygen, to the common currency of energy inside cells, i.e., ATP. Mitochondria contain their own private
DNA. In recent years several hereditary disorders have been shown to result from mutations in mitochondrial DNA
Genetics IV - Some Definitions
INHERITANCE (Autosomal dominant)
- a person called the CARRIER. Only one parent must be a carrier in order for a child to inherit the disease.
Proteins are complex organic compounds. The basic structure of protein is a chain
of amino acids that contain carbon, hydrogen, oxygen, and nitrogen. The presence of nitrogen differentiates protein from carbohydrate
is the main component of muscles, organs, and glands. Every living cell and all body fluids, except bile and urine, contain
protein. The cells of muscles, tendons, and ligaments are maintained with protein. Children and adolescents require protein
for growth and development.
names:chromosomes. Humans have 46 chromosomes. There are a total of 23 pairs of chromosomes or 46 total chromo-somes.
All of the body's genes are contained within these 46 chromosomes
GENE - Locus
Genes are the smallest units of heredity. The information
from all the genes, taken together, makes up the blueprint or plan for the human body and its functions.
A gene is
a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside
within long strands of DNA which in turn make up the chromosomes. Some diseases, such as sickle cell anemia, can be caused
by a change in a single gene (one out of the millions of genes which make up the plan for the entire human body).
are arranged in order along the DNA strand within the chromosome (similar to beads on a string). Matching genes from each
parent exist on matching chromosomes and matching positions along the DNA within the chromosome. These genes are paired, one
from the mother and one from the father.
Genes are described as DOMINANT or RECESSIVE. DOMINANT means that one
in the gene pair is able to control the trait which that gene pair codes for. RECESSIVE means that both genes in the gene
pair are necessary to control the trait.
Complex proteins that
cause a specific chemical change in other substances without being changed themselves. Enzymes exist in the mouth (saliva),
stomach (gastric juice), and intestines (pancreatic juice, intestinal juice, and intestinal mucosa); and change starches,
proteins, and sugars into substances the body can digest.
Enzymes also cause clotting (thrombin); split, reduce, or join other enzymes;
or remove amino groups during oxidation.
Genetics V - Autosomal dominant (HD)
names: inheritance (autosomal dominant); genetics (autosomal dominant)
single abnormal gene on one of the auto-somal chromosomes (one of the first 22 "non-sex" chromosomes) from either parent can
cause the disease. One of the parents will have the disease (since it is dominant) in this mode of inheritance and that person
is called the CARRIER. Only one parent must be a carrier in order for the child to inherit the disease.
The inheritance of genetic diseases, abnormalities, or traits is described by
the type of chromosome the abnormal gene resides on (autosomal or sex chromosome)
and by whether the gene itself
is dominant or recessive.
Autosomally inherited diseases are inherited through the non-sex chromosomes, pairs 1 through
22. Sex-linked diseases are inherited through one of the "sex chromosomes", the X chromosome (diseases are not inherited through
the Y chromosome).
Dominant inheritance occurs when an abnormal gene from ONE parent is capable of
even though the matching gene from the other parent is normal. The
abnormal gene dominates the outcome of the gene pair.
inheritance occurs when BOTH matching genes must be abnormal to produce
disease. If only one gene in the pair
is abnormal the disease is not manifest or is only
mildly manifest; however the disease can be passed on to the children.
STATISTICAL CHANCES OF INHERITING A TRAIT:
an autosomal dominant disorder: If one parent is a carrier and the other normal there is a 50% chance a child will inherit
In other words, if it is assumed that 4 children are produced, one parent is carrier and exhibits disease,
the STATISTICAL expectation is for:
2 children normal
2 children with the disease
This does not mean that
children WILL necessarily be affected; it does mean that EACH child has a 50:50 chance of inheriting the disorder.
Genetics VI - Counseling~ Prenatal Diagnosis/General
(Opinion of Adam.com Medical Library)
Genetic counseling and
Alternative names: prenatal diagnosis
over 4000 years, certain human abnormalities have been noted to run in families but the "WHY" of the observations did not
become apparent until the advent of modern genetics and the recognition of how genetic information is transmitted. Before
one only heard the admonition, "it's in the blood" (thought to refer more to bloodline
rather than some abnormal
element in the blood).
Present day medicine has recognized how genetic diseases are inherited based on an
of the nature of DNA, genes, and chromosomes. Scientists are presently
trying to "map" the chromosomes, to determine the
location and function of all of the millions of genes in each chromosome. This will ultimately help in treating genetic disorders.
until science has the ability to treat some of the more disastrous and ultimately
fatal genetic disorders the best remaining
recourse is prevention.
Prevention of genetically transmitted disease can consist of major choices: abstinence
from pregnancy, artificial insemination, prenatal diagnosis, and termination of affected pregnancies.
involves testing fetal cells, amniotic fluid, or amniotic membranes to
detect fetal abnormalities.
(and prenatal diagnosis) provides parents with the knowledge to make
intelligent, informed decisions regarding possible
pregnancy and its outcome.
Based on genetic counseling some parents, in the face of possibly lethal genetic
disease, have forgone pregnancy and adopted children while other have opted for artificial insemination from an anonymous
donor who is not a carrier of the specific disease.
Many diseases transmitted as a single gene defect can now be diagnosed
very early in
Because of this some parents have elected to become pregnant and then, early in the
pregnancy, had the disease status of the fetus determined. The pregnancy is continued if the fetus is disease-free.
Parents who decide to continue the pregnancy with a defective fetus may be able to
better prepare to care for the infant by being informed about the disease in advance.