|What You Need to Know About Genetics
Written by Ruth Papazian, MS
Reviewed by Gerry Klein, MD
The Human Genome Project (HGP) is an international research program initiated by
the U.S. Department of Energy and the National Institutes of Health in 1987 to
understand genetic heredity from one generation to the next.1 The main mission
of the HGP is to characterize the structure, organization and function of human
being accomplished with the creation of a map of the human genome that details
the nucleotide sequence of all 46 chromosomes, as well as the estimated 30,000
to 100,000 genes comprising our DNA.2
the past decade, genetic research has shown that most diseases arise from
genetic mutations or polymorphisms passed along from parents to children that
can result in a serious inherited disorder (such as Huntington's Disease),
predispose to a chronic condition (such as high blood pressure) or increase vulnerability
to infectious disease or to environmental toxins.
variations from one person to the next also affect responsiveness to medication
and susceptibility to treatment-limiting side effects - and help explain why
the same medication at the same dose improves one patient's symptoms, has no
effect on another patient's symptoms and may cause a severe adverse effect in a
researchers are examining the genomes of people who are helped and who are
harmed by particular medications to determine what the differences are between
these two groups at the molecular level. This type of research is called
instance, consider variation in a gene that codes for the production of an
enzyme that metabolizes (digests) a medication to treat high blood pressure. If
someone inherits a version of the gene that causes the body to pump out too
much of this enzyme, the medication would be metabolized and cleared from the
body too quickly to adequately lower blood pressure.
now use trial-and-error to determine which drug is the safest and most
effective for a particular patient, and some patients are switched from one
medication to another until they and their doctors are satisfied. The goal of pharmacogenetic research is to
enable doctors to practice "personalized medicine" - disease
prevention strategies and treatments devised for each individual patient based
on his or her one-of-a-kind genetic profile.
The ABCs of DNA and SNPs
you understand the basic concepts involved in genetic and pharmacogenetic
research, here's a list of terms you are likely to see in newspaper and
magazine articles on this Web site and elsewhere announcing new breakthroughs.
What is DNA?
(deoxyribonucleic acid) is the chemical of which genes and chromosomes are
made. DNA, which is found in every cell of your body, is a molecule made up of
two strands to which nitrogenous bases, known as nucleotides, are attached.
There are four nucleotides: adenine (A), thymine (T), guanine (G) and cytosine
(C). Like magnets that are attracted to each other, these bases pair up - A
with T and G with C - to hold the two strands together and cause them to wind
around each other like a twisted ladder.4 About five percent of DNA in a chromosome
consists of genes; scientists aren't yet sure what the rest of the DNA does.
Slideshow: What is DNA?
What is a gene?
are found on chromosomes. Each gene is a particle of DNA that determines the
characteristics, or traits, of an individual and are passed on from parent to
child.5 We have two copies of every gene, one from each parent. A gene is a
single component of a person's genome. The human genome is estimated to
comprise 30,000 to 100,000 genes, with each gene ranging in size from fewer
than one thousand to several million nucleotide bases.6
What do genes do?
gene consists of a sequence of nucleotides that encode instructions for making
a specific protein. Different sequences of adenine (A), thymine (T), guanine
(G) and cytosine (C) result in different proteins.
are essential to the structure and function of every cell in your body. For
instance, insulin regulates blood sugar, collagen keeps blood vessels elastic
and melanin gives hair and skin its color. Everyone has slightly different
versions of some genes that code for these and other proteins. In some cases,
genetic variations are linked to a disease or disorder - a mutation or
polymorphism in a gene involved in melanin production could cause albinism
(lack of pigment in the skin and hair). In other cases, polymorphisms are not
linked to a disease, as when different versions of a gene involved in melanin
production result in one person having blond hair, another having black hair
and a third having auburn hair.
What is a chromosome?
cells in your body contains a nucleus, which is where your chromosomes are
found. Each chromosome, which looks something like a Gummi worm, is made up of
protein and a single molecule of DNA. The normal human genome comprises two
sets of 23 chromosomes - one set from each parent. Among these 46 chromosomes is one pair of sex chromosomes that
determine gender (your mother can only pass on X chromosomes so if you got a
second X chromosome from your father, you're female and if you got a Y
chromosome from your father, you're male). The other 44 chromosomes are called
What do chromosomes do?
molecules are very long - consisting of anywhere from 50 to 250 million bases-
and chromosomes keep DNA tightly bundled in a neat package.
What is a polymorphism?
are sequence variations in DNA.7 The simplest type of sequence polymorphism is
a Single Nucleotide Polymorphism (or SNP, pronounced "snip"), in
which a nucleotide in a base pair is substituted for another nucleotide. When
this happens, a nucleotide sequence that might look like AACCAAG instead looks
like AACTAAG. Each of the two variations of the gene is called an allele.8
Polymorphisms involve alleles that occur in at least one percent of the
Slideshow: Polymorphism and Mutations
What is a mutation?
use the term "mutation" to refer to a harmful genetic variation
associated with a specific human disease or disorder. Like a polymorphism, a
mutation is a variation in DNA sequence - but mutations are rarer, occurring in
less than one percent of the population. Mutations cause cells to produce
proteins that function abnormally or are non-functional, which can result in disease or adverse
reaction to medicine.
What is a genome?
word "genome" was coined around 1930, and is a combination of
"gene" and "chromosome." A genome is the total amount of
DNA in the genes and chromosomes of a particular organism, typically expressed
in the number of base pairs. The normal human genome consists of three billion
base pairs. Since every cell in your body contains all 46 chromosomes, every
cell also contains your entire genome.9
What is a genotype?
for identical twins, everyone has his or her own unique genotype. One copy of
every chromosome - and all of the genes on it - is inherited from your mother
(via an egg cell), and the other copy is inherited from your father (via a
sperm cell). The gene inherited from Mom can have the identical base pair
sequence as the one inherited from Dad. Or each copy of the gene can have a
slightly different nucleotide sequence. It's the unique combination of genes
that are exact duplicates of each other and those that are slightly different
at a specific location on each set of chromosomes that make up a person's
What is a phenotype?
physical characteristics of a person make up his or her phenotype - which are
often, but not always, determined by his or her genotype.10 For instance, hair
color can be inherited or can be store-bought.
What is genome mapping and genome sequencing?
maps and genome sequences depict an individual's DNA in different ways. A
genome map identifies landmarks (such as short base sequences or regulatory
sites that turn genes on and off) that help scientists find specific genes on
your chromosomes.11 A genome sequence specifies the order of every nucleotide
base in every gene on every chromosome.12
are two kinds of genome maps - genetic maps and physical maps. Genetic maps
show the order of genes on a chromosome, and the relative distances between
those genes (the closer the genes, the more likely they will be inherited
together, or linked).13 Physical maps show the base pair distances from one
landmark to another.
How will genome sequencing and mapping help scientists figure out better ways of
preventing, diagnosing and treating disease?
Genome mapping and sequencing are complementary techniques that help scientists find
the locations of genes and polymorphisms. In particular, scientists are looking
for SNPs that:
Scientists are looking for genes and polymorphisms that determine individual response to
medication by affecting absorption, distribution, metabolism, excretion (ADME)
or toxicity. There may be as many as 100 such genes or polymorphisms, and
patients may one day be able to get screened for them the way they are screened
for high cholesterol. And doctors may be able to check a patient's genetic
profile to predict his or her response to a drug before it is prescribed.
- Help elucidate disease pathways and processes;
- Are associated with susceptibility to such complex, chronic diseases as diabetes
and heart disease - either as predictive indicators, or as drug targets; and
- Hamper the efficacy of medications, or cause adverse side effects.
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Guigo WT et al: Genome sequence comparisons: hurdles in the fast lane to
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Rojas K et al: Integration of the 1993-94 Genethon genetic linkage map for
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