Overview of biological functions

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation which depends on the same interaction between RNA nucleotides. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions between DNA and other molecules that mediate the function of the genome.

DNA damage

Benzopyrene, the major mutagen in tobacco smoke, in an adduct to DNA

DNA can be damaged by many different sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. In each human cell, about 500 bases suffer oxidative damage per day. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations.
Many mutagens fit into the space between two adjacent base pairs, this is called intercalating. Most intercalators are aromatic and planar molecules, and include ethidium, daunomycin, doxorubicin and thalidomide. In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators are often carcinogens, and benzopyrene diol epoxide, acridines, aflatoxin and ethidium bromide are well-known examples. Nevertheless, due to their ability to inhibit DNA transcription and replication, these toxins are also used in chemotherapy to inhibit rapidly-growing cancer cells.

Base modifications

The expression of genes is influenced by how the DNA ia packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions of that have low or no gene expression usually containing high levels of methylation of cytosine bases. For example, cytosine methylation, produces 5-methylcytosine, which is important for X-chromosome inactivation. The average level of methylation varies between organisms - the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, methylated cytosines are therefore particularly prone to mutations. Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastids

Chemical modifications

cytosine	5-methylcytosine	thymine

Structure of cytosine with and without the 5-methyl group. After deamination the 5-methylcytosine has the same structure as thymine

Quadruplex structures

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.
These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.

Alternative double-helical structures

DNA exists in many possible conformations. However, only A-DNA, B-DNA, and Z-DNA have been observed in organisms. Which conformation DNA adopts depends on the sequence of the DNA, the amount and direction of supercoiling, chemical modifications of the bases and also solution conditions, such as the concentration of metal ions and polyamines. Of these three conformations, the "B" form described above is most common under the conditions found in cells. The two alternative double-helical forms of DNA differ in their geometry and dimensions.
The A form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically-modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.

Supercoiling

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication

Sense and antisense

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.
A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

Base pairing

Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. The double helix is also stabilized by the hydrophobic effect and pi stacking, which are not influenced by the sequence of the DNA. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high . As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, left). The GC base pair is therefore stronger than the AT base pair. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called T_m value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others.

Major and minor grooves

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. Large version

The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove.

Physical and chemical properties

The chemical structure of DNA. Hydrogen bonds are shown as dotted lines.

DNA is a long polymer made from repeating units called nucleotides. The DNA chain is 22 to 26  Ångströms wide (2.2 to 2.6  nanometres), and one nucleotide unit is 3.3 Å (0.33 nm) long. Although each individual repeating unit is very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human chromosome, chromosome number 1, is approximately 220 million base pairs long.
In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules. These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. In general, a base linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. If multiple nucleotides are linked together, as in DNA, this polymer is called a polynucleotide.

The structure of part of a DNA double helix

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints or a recipe, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information

What if the coupe are not married?

When an unmarried couple have a child, the father must be present at the birth and sign a declaration stating he is the father. A DNA test is not required to put the father's name down on the certificate, but you can take a standard peace of mind DNA Paternity test to prove that he is the father, so you can comfortably put his name down without any doubts.

There is a six week window from when the child is born to the deadline for birth certificates to be handed in. This is a long enough time period for you to complete a DNA test and receive the results proving whether he is the father or not. In the event of the supposed father proven to not be the biological father, the mother reserves the right to leave the space on the certificate blank, without any penalty.

Fathers wanting to be named on Birth Certificate

For fathers not named on the birth certificate, they can seek legal advice if they believe themselves to be the biological father. If the mother is unwilling to put his name down on the certificate because she is unsure of the validity of his claims, a legal Paternity test can clear any doubt and help assist with the changing of the certificate. Even if he is proven to not be the father, the court can assess whether he has regular contact with the child and the quality of this contact, when they come to a decision regarding a change to the birth certificate.

Increased accuracy & stronger DNA test results.

Including the biological mother in DNA paternity testing and any DNA test strengthens dna test results. Wherever possible the mother should submit DNA samples as a participant and for this reason DNA Worldwide processes all mothers samples for FREE. Testing the mother's DNA increases the likelihood of a conclusive result for any DNA test - including DNA tests for paternity, siblings, or grandparents

WHY IS IT SO IMPORTANT?

DNA paternity tests analyzes up to 15 locations looking for matches between the alleged father and child. All markers must reflect a match (or mutation) or the alleged father is not the biological father. Each match receives an paternity index value indicating the strength of the match; the more unique the match, the higher the index. The probability of paternity is calculated using all of the paternity index values.

Most DNA paternity tests that examine only an alleged father and child show a conclusive probability of paternity: usually 99.99% when the alleged father is included as the biological father or 0% when he is not the father. In some cases, the matches between an alleged father and child provide an inconclusive result. Having the mothers DNA would provide a conclusive result.

In such instances, DNA Worldwide requests DNA samples for the biological mother. If she is unavailable, the test result remains inconclusive. With the mother, DNA paternity testing almost always provides a strong, conclusive result. Even when results are conclusive, including the mother further strengthens the DNA test conclusion.

The UK Government advise potential individuals seeking a DNA test for Paternity to always test the mothers DNA.

Case Studies

For example, consider the following case:
Locus Biological Mother
(not tested) Alleged Father Child Parentage Index
D2S1338 -- 12, 13 10, 12 1.845
D2S1358 -- 8, 11 11, 14 2.714
D8S1179 -- 21.2, 32 19, 21.2 2.675
D19S433 -- 15, 18 12, 15 7.338
In this case, the probability of paternity is 98.2896% (the product of all the parentage indexes). The result is inconclusive (because it must be greater than 99% or 0%), yet the alleged father and child match at all locations. Now, add the biological mother's sample to the DNA paternity test:
Locus Biological Mother
(Mother A) Alleged Father Child Parentage Index
D2S1338 8, 10 12, 13 10, 12 3.489
D2S1358 14, 17 8, 11 11, 14 5.114
D8S1179 15, 19 21.2, 32 19, 21.2 3.619
D19S433 8, 12 15, 18 12, 15 15.309
The probability of paternity increases to 99.9541%. Why? In the first example, one of the two markers from the child and alleged father match at each location. However, we don't know which of the child's markers comes from his mother and which must come from his father. By testing the child's mother, we see which of the child's markers must have come from the father. In the second table, the paternity index is increased.
Not only does the child match the alleged father, but the match is with the marker that must have come from the child's true biological father (since we can see which marker came from the child's mother). In fact, the index value is higher at each location because the biological mother participated in the DNA test.
But, what if the mother's DNA produced different markers?
Locus Biological Mother
(Mother B) Alleged Father Child Parentage Index
D2S1338 8, 12 12, 13 10, 12 0.000
D2S1358 14, 17 8, 11 11, 14 5.389
D8S1179 21, 21.2 21.2, 32 19, 21.2 0.000
D19S433 12, 15 15, 18 12, 15 0.786
With this data, the probability of paternity becomes 0%. The alleged father is not the child's biological father. The biological mother must match the chlid at all locations. We can see that this alleged father does not truly match the child's markers that must have come from the child's true biological father. In some places where he appeared to match the child's markers, the markers clearly come from the biological mother.
Note that there are still some matches between the alleged father and child. If this alleged father is truly the biological father, he must match at all locations (almost any two people will have at least some matches, but a father-child relationship will show matches at all locations). Even a few mismatches can be enough to exclude the alleged father from being the child's biological father. In this case, DNA testing the biological mother turns an inconclusive result to a definite "no" -

Married Couples

When a married couple have a child, the mother and the father are automatically placed on the birth certificate. This is because the government assumes that because the two are married, the father is the biological father. If there is any suspicion about this assumption, a DNA Paternity test can clear any doubts. A standard peace of mind Paternity test will not hold up in court anymore, so if you wish to remove the father's name from the birth certificate, you would need a legally recognised DNA test.

Under UK law, a person needs to give consent to have a DNA test. Taking someone's DNA without written consent is a legal offence and will cause all evidence to be null and void. When you do have written consent from the father, the procedure can go ahead with a simple cheek swab taken at your local GP or by an authorised nurse. After the results are produced, the court can then use this information when they decide to alter the certificate.

In addition to this, if there is another man who you do believe to be the biological father, you can issue legal DNA testing for him and his name could be added to the certificate, in the place of the original.

Changing the father's name on the Birth Certificate through a DNA test

Birth Certificates
The people named on a child's birth certificate are important because they gain parental responsibility for that child. It is important then, for the right people to be named. The process of altering a completed birth certificate is an important matter and requires the correct legal jurisdiction for it to be carried out. In many cases, a legal Paternity Test can help move along this process and put the matter behind you, so you and the father can raise the child in peace.

Ancestry DNA Testing Advice and Articles

Ancestry DNA Testing from DNA Worldwide is fast, accurate and confidential DNA with integrity and clarity. DNA Worldwide have put together this Ancestry Resource section to help provide information and answers to many of the common questions our customers have.

Consent to DNA Testing for Children Under 16

Taking a DNA test has life changing consequences, therefore we encourage both the mother and the father to be fully aware of any DNA test. However we understand their are circumstances when this is not possible.
Since the 1st September 2006 if you are having a DNA test carried out and are not submitting the mothers DNA for testing then a person with parental responsibility for the child must sign this consent form and send back with the DNA samples.
Q. How do I know if I have parental responsibility?
If the child was born from the 1 December 2003 onwards then new changes in the law mean unmarried fathers get equal parental responsibility. All you have to do is for both parents to register the birth of your baby together. If your child was born before this date then you could only gain parental responsibility by being married or marrying the child's mother, signing an official agreement with the mother or getting a court order.

DNA Testing & Consent

DNA and Genetic testing can potentially be life changing. For this reason it is essential that every individual who is having a DNA test carried out. Either on their own or as part of a DNA test (such as a Paternity Test) provides full and informed consent to testing.
This means that the person is fully aware of the type of DNA test that is being carried out and the potential outcomes of the test.
If a child (under the age of 16 in the UK) is being tested, then a person with fu
ll parental responsibility must sign consent on behalf of the child.