DNA Testing Basics
There are about 100 trillion cells in the adult human body.
Most of them have a nucleus, or center, that contains threadlike
bundles of chromosomes. In these chromosomes are all of the instructions
and information needed to make a human being. Each parent contributes
one chromosome to each of the 23 pairs found in all normal people.
Within the chromosomes, are up to 100,000 paired genes, the fundamental
units of heredity. Each gene can have different versions (as
many as 100 or more in rare cases) called alleles, but most are
the same from person to person. Genes determine all inherited
traits including those that give the individual specific characteristics
(blue eyes rather than brown eyes) as well as common characteristics
(two eyes, two arms, etc.).
Genes are made of deoxyribonucleic acid (DNA). Hence, DNA is
the master molecule of life and controls the growth and development
of every living thing. It is a polymer, i.e., a long string of
simple repeating units. These repeating units are called nucleotides
and are of four types: adenine (A), cytosine (C), guanine (G),
and thymine (T). Just as the order of the letters of the alphabet
determines the information content of words, the order in which
these four bases are strung together is what gives DNA its information
content. The complete DNA molecule consists of two of these strands
of the four bases.
In the two strands, A always is across from or paired with T
and G always is paired with C. These are the base pairs that
are the unit of measurement in determining the size of a given
segment of DNA. This structure suggests a natural mechanism for
the duplication or replication of the DNA molecule, as occurs
during cell division. These pairings are what connect the two
strands of DNA together to form a tightly coiled, twisted ladder.
This spiral staircase, the famous double helix, is the natural
form in which DNA is found within the nucleus of the cells.
If uncoiled, the DNA molecules in every human cell would measure
six feet in length. That is the total length of the 3.3 billion
base pairs that make up the total human genetic complement or
genome. Except for identical twins, the sequence of the base
pairs within the DNA helix is unique for every person, and forms
the individual's genetic code or blueprint.
Perhaps the basis of DNA typing can be best understood by comparing
the way in which genetic information is stored in the DNA to
the way in which printed information is stored in books. For
example, if we were to cut all the sentences in forty volumes
of the Encyclopedia Britannica into strips, and tape them together
end to end, then we would have an amount of information equivalent
to that contained in the DNA within each of the cells that make
up our bodies. Furthermore, the information would then be in
the same physical form as the DNA information, i.e., a long linear
strip sometimes likened to a computer punch tape.
The genetic information contained in the DNA is organized and
packaged into chromosomes, much as printed information is organized
into volumes. Just as a specific passage in the encyclopedia
can be identified by specifying a volume, page, and line number,
a specific genetic passage or location, known as a locus, can
be identified. A specific naming system identifies genes by numbers
issued by the Human Gene Mapping Committee. For example, if we
see the designation D4S139 in a report, then we know exactly
what gene has been analyzed, that it is on chromosome four, and
that it is the 139th DNA probe to be mapped to chromosome four.
A significant difference between the way information is stored
in the cell and in the encyclopedia is that there are two copies
of the information in each of the cells, one from the mother
and one from the father. These two copies of the genetic information
which are largely identical, come together at the moment of conception
when the sperm and the egg join together. All of the child's
cells contain DNA derived from this original fertilized cell,
half from the mother and half from the father. It is this basic
principle of heredity, first discovered over 150 years ago, that
allows us to reliably perform parentage tests.
Human sex is determined by the X and Y chromosomes. A female
has 2 X-Chromosomes and a male has an X and a Y-Chromosome. When
a child is conceived it gets one chromosome from its mother and
one chromosome from its father. The chromosome from the mother
will always be an X, but the chromosome from the father may be
either X or Y. If the child gets the X she will a girl, if the
child gets the Y he will be a boy.
Different parts of DNA have different rates of mutation. Analyzing
areas that have high or low mutation rates give us specific information
for a variety of purposes including DNA identity testing, diagnosis
of medical genetic conditions, and tracing of deep ancestral
roots.
Definitions
Allele: One of the variant forms of a gene at a particular locus,
or location, on a chromosome. Different alleles produce variation
in inherited characteristics. For STR markers, each allele is
the number of repeats of the short base sequence.
Base Pair: Two bases that form a "rung of the DNA ladder." A
DNA nucleotide is made of a molecule of sugar, a molecule of
phosphoric acid, and a molecule called a base. The bases are
the "letters" that spell out the genetic code. In DNA,
the code letters are A, T, G, and C, which stand for the chemicals
adenine, thymine, guanine, and cytosine, respectively. In base
pairing, adenine always pairs with thymine, and guanine always
pairs with cytosine.
Chromosome: Chromosomes are paired threadlike "packages" of
long segments of DNA contained within the nucleus of each cell.
In humans there are 23 pairs of chromosomes. In 22 pairs, both
members are essentially identical, one deriving from the individual's
mother, the other from the father. The 23rd pair is different.
In females this pair has two like chromosomes called "X".
In males it comprises one "X" and one "Y," two
very dissimilar chromosomes. It is these chromosome differences
which determine sex.
DNA: The chemical inside the nucleus of a cell that carries
the genetic instructions for making living organisms.
DYS#: D=DNA, Y=Y chromosome, S=a unique DNA segment. A label
for genetic markers on the Y chromosome. Each marker is designated
by a number, according to international conventions. At present,
virtually all the DYS designations are given to STR markers (a
class often used in genetic genealogy).
Gene: The functional and physical unit of heredity passed from
parent to offspring. Genes are pieces of DNA, and most genes
contain the information for making a specific protein.
Genome: All the DNA contained in an organism or a cell, which
includes both the chromosomes within the nucleus and the DNA
in mitochondria.
Locus: A point in the genome, identified by a marker, which
can be mapped by some means. It does not necessarily correspond
to a gene. A single gene may have several loci within it (each
defined by different markers) and these markers may be separated
in genetic or physical mapping experiments. In such cases, it
is useful to define these different loci, but normally the gene
name should be used to designate the gene itself, as this usually
will convey the most information.
Marker: Also known as a genetic marker, a segment of DNA with
an identifiable physical location on a chromosome whose inheritance
can be followed. A marker can be a gene, or it can be some section
of DNA with no known function. Because DNA segments that lie
near each other on a chromosome tend to be inherited together,
markers are often used as indirect ways of tracking the inheritance
pattern of genes that have not yet been identified, but whose
approximate locations are known.
Microsatellite: Repetitive stretches of short sequences of DNA
used as genetic markers to track inheritance in families.
Mutation: A permanent structural alteration in DNA.
Short Tandem Repeats (STR): A genetic marker consisting of multiple
copies of an identical DNA sequence arranged in direct succession
in a particular region of a chromosome. Occasionally, one will
mutate by the gain or loss of one repeat. (Also known as microsatellite)
Single Nucleotide Polymorphism (SNP): common DNA sequence variations
among individuals.
Ancestry DNA Testing
Ancestry DNA Testing infers your Biological Ancestry proportions
by utilizing novel Single Nucleotide Polymorphisms (SNPs, pronounce
SNIPS) called Ancestry Informative Markers (AIMs). Though we
are 99.9% identical at the level of our DNA, it is that 0.1%
that imparts to us our individuality. AIMs are places in that
0.1% of the human genome that differ in sequence between the
world's various populations (most of the 0.1% do not differ in
this way), and by reading a persons sequence at these positions
it is possible to make a strong inference of their ancestral
mix. Using recent genomics advances, scientists have identified
the world's only comprehensive set of AIMs. The science behind
the tests was published in late 1999, and then again in 2001
and 2002 (Parra et al.1; Pfaff et al. 2; Parra et al., 3 and
Frudakis et al. 4). The resulting Ancestry DNA Test is the first
product yet developed that enables the determination of individual
ancestry proportions (called "admixture ratios") from
DNA. Because it uses genetic markers spread throughout all the
chromosomes, with unique and specific anthropological characteristics,
it is quite a distinct product from STR tests, Y-chromosome tests
or mitochondrial DNA tests used in other types of anthropological
settings. Prior to this testing, there had existed only one DNA
test for "race". It too used markers spread among the
chromosomes, but only 8-13 (as opposed to hundreds), and using
the test has a number of technical and theoretical limitations.
For example, using the common human identity tests (STR tests)
for the inference of ancestry, it is not possible to discern
the difference between an individual of 60% African, 40% European
heritage and an individual of 95% African, 5% European heritage
(or any other race/percentage combination). Instead, it is only
possible to classify a sample as having been derived from an
individual of one group - in this example, the result in both
cases would be an African inference. Part of the problem with
the existing STR tests is that they suffer from statistical,
practical and ethical problems because they use overly-complex
markers to rigidly "bin" individuals into single racial
groups. Most individuals are, in fact, of mixed racial background,
and ANCESTRY is the first test ever capable of revealing the
precise ancestral proportions within each individual. As such,
the test simply reports proportions, rather than making dubious
racial classifications.
Admixture proportions are the precise mixture of ancestry within
individuals. For example, though a person may seem to be of African
heritage, the person may actually be of 80% African and 20% Indo-European
ancestry, or they may be of 95% African and 5% Indo-European
ancestry, or some other ratio/mix. ANCESTRY gives the precise
answer by querying a large number of positions in the person's
DNA and using them to plot the individual along "A Multi-Dimensional
Continuum of Ancestry" TM. The test has a sensitivity for
sub-Saharan African, Indo-European, East Asian and Native American
ancestries.
Our current product, produces 4-dimensional plots for representing
individual ancestry proportions in terms of Indo-European, sub-Saharan
African, Native American and East Asian. If a person is of significant
levels of each of the four, the plot is difficult to represent
on paper, but the meaning of the raw data generated from this
test is the same and this data is easily presented in a spreadsheet
format. If the customer is of three or fewer, they can easily
be plotted in the triangle plot, and both this plot and the spreadsheet
are provided.
Articles:
1 - Parra, E., Marcini, A., Akey, J., Martinson, J., Batzer,
M., Cooper, R., Forrester, T., Allison, D., Deka, R., Ferrell,
R. and M. Shriver. 1998. Estimating African American Admixture
Proportions by Use of Population Specific Alleles. Am. J. Hum.
Genet. 63:1839-1851.
2- Pfaff, C., Parra, E., Bonilla, C., Hiester, K., McKeigue,
P., Kamboh, M., Hutchinson, R., Ferrell, R., Boerwinkle, E.,
and M. Shriver. 2001. Population Structure in Admixed Populations:
Effect of Admixture Dynamics on the Pattern of Linkage Disequilibrium.
Am. J. Hum. Genet. 68:198-207.
3- Parra, E., Kittles, R., Argyropoulos, G., Pfaff, C., Hiester,
K., Bonilla, C., Sylvester, N., Parrish-Gause, C., Garvey, W.,
Jin, L., McKeigue, P., Kamboh, M., Ferrell, R., Pollitzer, W.,
and M. Shriver. 2001. Ancestral Proportions and Admixture Dynamics
in Geographically Defined African Americans Living in South Carolina.
American Journal of Physical Anthropology 114:18-29.
4- Frudakis, T., V Kondragunta, M Thomas, Z Gaskin, S Ginjupalli,
S Gunturi, V Ponnuswamy, S Natarajan, and P Nachimuthu. 2002.
A Classifier for SNP-Based Racial Inference. In Review, Journal
of Forensics Sciences.
Start unraveling the mystery of your DNA and heritage today,
call 800-523-3080 to order your Ancestry DNA Test for only $445,
order on-line, or download the order form and fax or mail in
your order. Don't forget to take a look at our other informational
genetic testing products now as you receive significant discounts
when ordering tests at the same time.
Common Male Ancestor Test
Our Common Male Ancestor Test examines 26 markers on the Y-Chromosome.
The Y-Chromosome has several unique features that make it useful
to genealogists including:
The presence of a Y-Chromosome causes maleness. This little
chromosome, about 2% of a father's genetic contribution to his
sons, programs the early embryo to develop as a male.
It is transmitted from fathers only to their sons.
Most of the Y-Chromosome is inherited as an integral unit passed
without alteration from father to sons, and to their sons, and
so on, unaffected by exchange or any other influence of the X-Chromosome
that came from the mother. It is the only nuclear chromosome
that escapes the continual reshuffling of parental genes during
the process of sex cell production.
Testing the Y-Chromosome
The Y-Chromosome has definable segments of DNA with known genetic
characteristics. These segments are known as Markers. These markers
occur at an identifiable physical location on a chromosome known
as a Locus. Each marker is designated by a number (known as DYS#),
according to international conventions. You will often find the
terms Marker and Locus used interchangeably, but technically
the Marker is what is tested and the Locus is where the marker
is located on the chromosome.
Although there are several types of markers used in DNA studies,
the Y-Chromosome test uses only one type. The marker used is
called a Short Tandem Repeat (STR). STRs are short sequences
of DNA, (usually 2, 3, 4, or 5 base pairs long), that are repeated
numerous times in a head-tail manner. The 16 base pair sequence
of "gatagatagatagata" would represent 4 repeats of
the sequence "gata". These repeats are referred to
as Allele. The variation of the number of repeats of each marker
enables discrimination between individuals.
What Does it Mean
An individual's test results have little meaning on their own.
You cannot take these numbers, plug them into some formula and
find out who your ancestors are. The value of the test results
depends on how your results compare to other test results. And
even when you match someone else, it will only indicate that
you and the person you match share a common ancestor. Depending
on the number of markers tested and the number of matches it
will indicate with a certain degree of probability how long ago
this common ancestor existed. It will not show exactly who this
ancestor is.
As discussed above, the Y-Chromosome is passed from father to
son. The vast majority of the time the father passes an exact
copy of his Y-Chromosome to his son. This means that the markers
of the son are identical to those of his father. However on rare
occasion there is a mutation or change in one of the markers.
The change is either an insertion or a deletion. An insertion
is when an additional repeat is added to a marker. A deletion
is when one of the repeats is deleted.
Mutations occur at random. This means it is possible for two
distant cousins to match exactly on all markers while two brothers
might not match exactly. Because of the random nature of mutations
we must use statistics and probability to estimate the Time to
the Most Recent Common Ancestor (TMRCA). The actual calculations
of TMRCA are mathematically complex and depend on knowing the
rate of mutation and the true number of mutations. At this time
there is not enough data to accurately determine either of these
factors so certain assumptions have to be made. The discussion
of these assumptions and the actual calculations are beyond the
scope of this webpage. For those wishing to read more about the
various models used, I recommend Time to Most Recent Common Ancestry
Calculator by Bruce Walsh. The simplest and one of the most commonly
used models makes the following assumptions:
Rate of Mutation = .002. This assumes that any given marker
has a .002 chance of mutating with each generation. In other
words, we could expect any marker to mutate once in 500 generations.
The rate of .002 is considered conservative and is the average
of a number of studies. It will result in a TMRCA that is longer
than higher mutation rates.
Number of mutations: This model counts any change in a marker
as a single mutation. Each marker is scored as either a match
or a non-match. If a marker does not match it is assumed to be
a single mutation. This method a counting mutations may result
in underestimating the TMRCA.
Based on the above assumptions we derive the cumulative probability
table below. This table simply list the number of generations
corresponding to the 50%, 90% and 95% probability levels for
various numbers of matches.
Match 50% 90% 95% 95% Confidence Interval
25-0 Match exactly at all 25 markers
7 23 30 0-37
24-1
24 exact matches, 1 mismatch
17 40 48 2-57
23-2 23 exact matches, 2 mismatch
28
56 66 6-75
This table tells us that if we match on 24 of 25 markers there
is a 50% probability that the most recent common ancestor is
17 generations or less, a 90% probability that TMRCA is 40 generations
or less, and a 95% probability that TMRCA is 48 generations or
less. The 95% Confidence Interval is the upper and lower range
of values that encompass 95% of the probability for the TMRCA.
If we match on 24 of 25 markers, 95% of the possible TMRCA values
fall between 2 and 57 generations.
As you can see from the above table more markers reduce the
number of generations to TMRCA. The Chart below shows how increasing
the number of markers tested, decreases the number of generation
to TMRCA when all markers match.
Putting It All Together
DNA testing can be a valuable tool in genealogical research
when it is combined with conventional research. Test results
can be used to confirm a suspected connection between two families
or disprove a connection. Although it is impossible to pinpoint
a common ancestor from the test results alone, with a proper
paper trail you may be able to do so.
Common Female Ancestor Test
The DNA in a cell's mitochondria has already been fully mapped
and found to contain only 37 genes, all of them inherited solely
from our mothers (instead of the complicating mix from both parents
that occurs in the nucleus). Each person's mitochondrial DNA
is a copy of their mother's, their grandmother's and so on -
a maternal thread that reaches back to the dawn of the species.
Because mitochondrial DNA mutates more rapidly than regular
genes, scientists have been able to track the rate of such changes,
making it possible to identify individual bloodlines. There are
2 regions of the mtDNA that are of particular interest to researchers
because of their variability among the different human populations.
These regions are most commonly referred to as HVR1 and HVR2.
To characterize the HVR1 mtDNA pattern, Genelex sequences the
mtDNA. We then provide mtDNA sequence data and comparative analysis
through examining this region, and report the differences as
compared to a standard, the Cambridge Reference Sequence.
Genelex offers this service to facilitate in reconstructing
family maternal-linked relationships. However, the data can also
be used to research your own mtDNA sequence. There are a number
of publications that will assist you with researching your mtDNA
profile and how it relates to published mtDNA migration patterns.
Disclaimer
The content of this web site is for public use, free of charge,
and for information only. It is not intended to be used in
any other way. The authors disclaim any liability, loss, injury,
or damage incurred as a consequence, directly or indirectly,
of the use and application of any of the content of this web
site.
The information presented on this site is intended as general
health information and as an educational tool. It is not intended
as medical advice. Only a physician, pharmacist, or other healthcare
professional should advise a patient on medical issues and
should do so using a medical history and other factors identified
and documented as part of the health professional/patient relationship.
