All About Genetics





What do you know about your family tree? Have any of your relatives
had health problems that tend to run in families? Which of these
problems affected your parents or grandparents? Which ones affect you or
your brothers or sisters now? Which problems might you pass on to your
children?

Thanks to advances in medical research, doctors now have the tools to
understand much about how certain illnesses, or increased risks for
certain illnesses, pass from generation to generation. Here are some
basics about genetics.

Genes and Chromosomes



Each of us has a unique set of chemical blueprints affecting how our
body looks and functions. These blueprints are contained in our DNA
(deoxyribonucleic acid), long, spiral-shaped molecules found inside
every cell. DNA carries the codes for genetic information and is made of
linked subunits called nucleotides. Each nucleotide contains a
phosphate molecule, a sugar molecule (deoxyribose), and one of four
coding molecules called bases (adenine, guanine, cytosine, or thymine).
The sequence of these four bases determines the genetic code.

The specific segments of DNA that contain the instructions for making
specific body proteins are called genes. Right now, scientists believe
that human DNA carries from 25,000 to 35,000 genes. Some genes direct
the formation of proteins that eventually determine physical features
such as brown eyes or curly hair. Others provide instructions for the
body to produce important chemicals called enzymes (which help control
the chemical reactions in the body).

Sometimes, depending on the codes of a specific gene, even a small
error within the DNA structure can mean serious problems for the entire
body. Sometimes, an error in just one gene can result in a life that's
shortened or physically difficult.

Genes are found in specific segments along the length of human DNA,
neatly packaged within structures called chromosomes. Every human cell
contains 46 chromosomes, arranged as 23 pairs (called autosomes), with
one member of each pair inherited from each parent at the time of
conception. After conception, the chromosomes duplicate again and again
to pass on the same genetic information to each new cell in the
developing child. Twenty two autosomes are the same in males and
females. In addition, females have two X chromosomes and males have one X
and one Y chromosome. The X and the Y are known as sex chromosomes.

Human chromosomes are large enough to be seen with a high-powered
microscope, and the 23 pairs can be identified according to differences
in their size, shape, and the way they pick up special laboratory dyes.Genetic Problems



Abnormal Numbers of Chromosomes (Trisomies and Monosomies)



Genetic problems can happen for many reasons. Sometimes, a mistake
occurs during cell division, causing an error in the chromosome number
either before or shortly after conception. The developing embryo then
grows from cells that have either too many chromosomes or too few.

In trisomy, for example, there are three copies of
one particular chromosome instead of the normal two (one from each
parent). Down syndrome, trisomy 18 (Edwards) syndrome, and trisomy 13
(Patau) syndrome are examples of this type of genetic problem.

Trisomy 18 syndrome affects 1 out of every 3,000 newborns. Children
with this syndrome have a low birth weight and a small head, mouth, and
jaw. Their hands typically form closed fists with abnormal finger
positioning. They also might have malformations involving the hips and
feet, heart and kidney problems, and intellectual disability (also
called mental retardation). Only about 5% of these children live longer
than 1 year.

Trisomy 13 syndrome affects 1 out of every 5,000 newborns. This
syndrome causes cleft lip, flexed fingers with extra digits, hemangiomas
(blood vessel malformations) of the face and neck, and many different
structural abnormalities of the skull and face. It can also cause
malformations of the ribs, heart, abdominal organs, and sex organs.
Long-term survival is unlikely but possible.

In monosomy, another form of number error, one member of a chromosome pair is missing. There are too few chromosomes rather than too many.

Deletions, Translocations, and Inversions



Sometimes it's not the number of chromosomes that's the problem, but
that chromosomes are incomplete or abnormally shaped. In both deletions and microdeletions,
for example, some small part of a chromosome is missing. In a
microdeletion, the missing part of a chromosome is usually so small that
it amounts to a single gene or only a few genes.

Important genetic disorders caused by deletions and microdeletions
include Wolf-Hirschhorn syndrome (affects chromosome 4), Cri-du-chat
syndrome (chromosome 5), DiGeorge syndrome (chromosome 22), and Williams
syndrome (chromosome 7).

In translocations (which affect 1 out of every 500
newborns), bits of chromosomes shift from one chromosome to another.
Most translocations are "balanced," which means there is no net gain or
loss of genetic material; some are "unbalanced," which means some
genetic material is extra or missing.With inversions
(which affect about 1 out of every 100 newborns), small parts of the DNA
code seem to be snipped out and reinserted flipped over. Translocations
may be either inherited from a parent or arise spontaneously in a
child's own chromosomes.

Both balanced translocations and inversions typically cause no
malformations or developmental problems in the kids who have them.
However, adults with either translocations or inversions who wish to
become parents may have an increased risk of miscarriage or chromosome
abnormalities in their own children. Unbalanced translocations or
inversions are associated with developmental and/or physical
abnormalities.Genetic Problems (cont.)



Sex Chromosomes



Genetic problems also occur when abnormalities affect the sex
chromosomes. Normally, a child will be a male if he inherits one X
chromosome from his mother and one Y chromosome from his father. A child
will be a female if she inherits a double dose of X (one from each
parent) and no Y.

Sometimes, however, children are born with only one sex chromosome
(usually a single X) or with an extra X or Y. Turner syndrome is the
name of the disorder affecting girls born with only one X chromosome,
whereas boys with Klinefelter syndrome are born with XXY or XXXY.

Sometimes, too, a genetic problem is X-linked,
meaning that it's associated with change in a gene carried by the X
chromosome. Fragile X syndrome, which causes intellectual disability in
boys, is one such disorder. Other diseases that are carried by genes on
the X chromosome include hemophilia and Duchenne muscular dystrophy.

Females may be carriers of these diseases, but because they also
inherit a normal X chromosome, the effects of the gene change on the
affected X will be reduced. Males, on the other hand, only have one X
chromosome and are almost always the ones who have the substantial
effects of the X-linked disorder.

Gene Mutations



Some genetic problems are caused by a single gene that's present but altered in some way. Such changes in genes are called mutations.
When there is a mutation in a gene, the number and appearance of the
chromosomes is usually still entirely normal. To pinpoint the defective
gene, scientists use sophisticated DNA screening techniques. Some
examples of genetic illnesses caused by a single problem gene include:
phenylketonuria (PKU), cystic fibrosis, sickle cell anemia, Tay-Sachs
disease, and achondroplasia (a type of dwarfism).

Although experts originally believed that no more than 3% of all
human diseases were caused by errors in a single gene, new research
suggests that this may be an underestimate. Within the last few years,
scientists have discovered genetic links to many different diseases that
weren't originally thought of as genetic, including several different
types of cancer.

Oncogenes (Cancer-Causing Genes)



Researchers have identified 20 to 30 cancer-susceptibility genes that
greatly increase a person's odds of getting some form of malignancy.
For example, a gene on chromosome number 9 may be linked to basal cell
carcinoma, a common skin cancer. This gene, labeled PTC or patched,
someday might be important in screening for this type of cancer. Another
gene (HNPCC) that is carried by 1 out of every 300 Americans might
greatly increase someone's risk for colon cancer. And the doubly
dangerous gene BRCA-1 seems to give women an 85% chance of developing
breast cancer as well as a 50% chance of ovarian tumors.Other Genetically Linked Diseases



Altered genes may play a role in the development of many other
devastating illnesses. Parkinson's disease, for example, may be linked
to a gene on chromosome number 4, and multiple sclerosis may be linked
to alterations in a gene on chromosome number 6. Alzheimer's disease,
linked to a gene on chromosome 19, can already be diagnosed (in some
cases) by screening for that altered gene, although such screening is
viewed by many as controversial.

Although heart disease and diabetes appear to be related to
simultaneous changes in many different genes, the first of these may
already have been identified. According to the American Heart
Association, this gene may be an artery-clogging gene that almost
doubles the risk of fatty deposits blocking the coronary arteries.
Having the gene may also triple someone's chances of getting adult-onset
diabetes.

It's important to note that much of the newest information from
genetic research has not yet been translated into useful screening
tests. However, experts predict that this will soon change, and they
estimate that the number of available genetic tests will increase
dramatically in the years to come.