Explainer: How DNA testing works | Science News for Students

Explainer: How DNA testing works

Whether this sequencing ‘reads’ out all of the DNA depends on what test kit was used
Oct 24, 2019 — 6:40 am EST
a photo of an open mouth about to be swabbed with a cotton swab

Open wide! Scientists can learn about your DNA when you buy a kit and then send a swab or tube of your saliva back to the company. 

PeJo29/iStock/Getty Images Plus

Want to find out more about yourself, your family or even your pet? There’s a DNA test for that. Spit in a tube. Let your dog chew a swab. Or pull out some of your cat’s fur. Then ship that sample off in the mail. A few weeks later, you can log into a testing company’s website to get a guide describing the traits suggested by that DNA.

The findings might predict someone’s hair color or suggest whether your genes will make you think the herb cilantro tastes like soap (though if you’ve tasted it, you probably already know what you think). The testing might go on to turn up relatives you didn’t know you had. If you got it for your dog, the test might say whether Fido has any German shepherd, corgi or poodle in its family tree. It might also identify whether you or your dog faces an elevated risk for certain diseases (such as kidney problems).

Such wizardry is known as DNA sequencing. It allows scientists to figure out the order of the “letters” in a DNA molecule. Those letters — called nucleotides — are the chemicals that make up DNA.

There are only four letters: adenine (A), cytosine (C), thymine (T) and guanine (G). Adenine only pairs with thymine. Cytosine only pairs with guanine. This might seem like a very limited alphabet. But the order in which those letters line up within a long string of DNA will spell out genetic instructions that tell each cell of the body which molecules it should make. And there’s plenty of space for long “words.” In humans, dogs and cats, each strand of DNA runs about 6 billion letters long.

Portions of each strand are known as sequences (as in sequences of letters). Decoding the letters in a strand is known as “sequencing” the genetic code. The letters’ precise ordering will change from one individual to the next. Still, the “words” — the instructions the sequences produce — tend to be similar between all members of a species.

Scientists can compare the order of all those letters in one person’s DNA to those in someone else’s. With billions of nucleotides, millions of those letters are going to be different, even between parents and children or brother and sister.

For instance, some people have one letter — say an A — at the place in some sequence where others might have a G or C. Some of those switched letters can alter a gene’s meaning. The new spelling might cause the gene to make a different protein. One tiny spelling tweak could contribute to making you taller or change the color of your eyes. Another might put you at a higher or lower risk for some disease. When compared to someone else, the precise spelling of sequences in your DNA can show how closely related you two are.

There are many companies that will test DNA — for you and even your cat or dog (no fish, gerbils or birds, yet). But all DNA tests are not created equal. What you learn about your genetic makeup depends on the company you choose and the level of testing it does. There are three main types of tests.

an illustration showing three different levels of genome sequencing
This graphic shows the three main levels of DNA testing that people can currently buy. Level 1 is whole genome sequencing. Level 2 focuses on the exome, that part of the DNA that makes proteins. Level 3 scouts for SNPs — single DNA-letter changes.
Graphic: E. Otwell; Source: Veritas Genetics, Genos

1. The whole shebang (almost)

In theory, whole genome sequencing captures all of the 6 billion nucleotides in a genome (GEE-noam) — an organism’s complete set of genes. These companies will have gone through and tried to “read” every A, C, T and G. In reality, they will miss some (as if they were speed-reading and skipped a letter or word now and again). When DNA is packed together into organized units called chromosomes (KROH-moh-soams), it’s easy to miss a letter or two. In the image above, zooming in on the gold bars under chromosome 12 shows such testing gaps.

Whole-genome sequencing will not detect large chunks of missing or re-arranged DNA. It also might miss when a section of DNA has been repeated over and over. Still, this approach gives the most complete view of someone’s particular genes. Companies such as Veritas Genetics offer this testing for people (if prescribed by a doctor). In pets, Darwin’s Ark offers whole-genome sequencing for dogs.

2. Focus on the proteins

DNA contains a lot of letters. But not all of the “words” mean something. Some sequences make proteins. Others may control how often other DNA sequences are turned on to make those proteins. Still others might provide instructions for molecules that are not proteins. Or they might just be sequences full of nonsense that “say” nothing at all.

The exome is that part of a genome that holds protein-coding genes. It makes up only about 1 to 2 percent of someone’s DNA. In the diagram above, the exome appears blue.

Exome sequencing generally does not offer information on genetic tweaks that might turn other genes on or off. It also doesn’t include genes that aren’t used to make a protein. But just because it doesn’t make a protein doesn’t mean some gene doesn’t have a job. Many genes play important roles without making proteins at all. Genos and Helix are two companies offer sequence human exomes. Helix also reads some of the DNA next to protein-coding genes.

3. The minimalist approach

A third type of test looks at SNPs (pronounced “snips”). That’s short for single nucleotide polymorphisms (NU-klee-oh-tyde Pah-lee-MOR-fizms). These tests scout for single-letter misspellings sprinkled throughout your genome.

Where most people have an A, for instance, a minority may have a C. Over time, scientists have identified collections of these SNPs and grouped tests to find them together into single tests called SNP chips, or genotyping arrays.

These can take a sample of an animal’s (or person’s) DNA and test for a preset group of SNPs that are known to be involved in certain traits. Companies can test hundreds, thousands — even millions — of SNPs at a time with these tests. But that’s still only a tiny fraction of the letters in your genome. Ancestry, 23andMe and many other companies rely on these SNP tests to interpret human DNA. Wisdom Panel, homeDNA and emBark do the same for dogs. Wisdom Panel, Optimal Selection and homeDNA use SNPs to look for the ancestral breeds behind any cat.

One gene at a time

You can buy most of these tests without a doctor’s order. But sometimes doctors may want patients to get tested for DNA changes in one or a few genes — alterations that might up an individual’s risk of disease. For people, those tests will take a really close look at the DNA around that gene and decipher the changes that only one person has.

For pets, the University of California, Davis and some other places can check for changes in genes that may cause problems for certain canine and feline breeds. That allows dog breeders to keep vulnerable animals from mating — and passing along their misspelled genes.

Power Words

(more about Power Words)

array     A broad and organized group of objects. Sometimes they are instruments placed in a systematic fashion to collect information in a coordinated way. Other times, an array can refer to things that are laid out or displayed in a way that can make a broad range of related things, such as colors, visible at once. The term can even apply to a range of options or choices.

breed     (noun) Animals within the same species that are so genetically similar that they produce reliable and characteristic traits. German shepherds and dachshunds, for instance, are examples of dog breeds. (verb) To produce offspring through reproduction.

cancer     Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.

cell     The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.

chemical     A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.

chromosome     A single threadlike piece of coiled DNA found in a cell’s nucleus. A chromosome is generally X-shaped in animals and plants. Some segments of DNA in a chromosome are genes. Other segments of DNA in a chromosome are landing pads for proteins. The function of other segments of DNA in chromosomes is still not fully understood by scientists.

coding     (in genetics) The instructions contained in DNA (or its genes) that allow a cells to know what proteins to make and when to make them.

DNA     (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

gene     (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

genetic     Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.

genome     The complete set of genes or genetic material in a cell or an organism. The study of this genetic inheritance housed within cells is known as genomics.

guanine     One of four substances that organisms need to produce DNA.

helix     An object with a three-dimensional shape like that of a wire wound uniformly in a single layer around a cylinder or cone, as in a corkscrew or spiral staircase.

information     (as opposed to data) Facts provided or trends learned about something or someone, often as a result of studying data.

molecule     An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).

nucleotides     The four chemicals that, like rungs on a ladder, link up the two strands that make up DNA. They are: A (adenine), T (thymine), C (cytosine) and G (guanine). A links with T, and C links with G, to form DNA. In RNA, uracil takes the place of thymine.

organism     Any living thing, from elephants and plants to bacteria and other types of single-celled life.

protein     A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.

risk     The chance or mathematical likelihood that some bad thing might happen. For instance, exposure to radiation poses a risk of cancer. Or the hazard — or peril — itself. (For instance: Among cancer risks that the people faced were radiation and drinking water tainted with arsenic.)

sequence     The precise order of related things within some series. (in genetics) n. The precise order of the nucleotides within a gene. (v.) To figure out the precise order of the nucleotides making up a gene.

sequencing     Technologies that determine the order of nucleotides or letters in a DNA molecule that spell out an organism’s traits.

single nucleotide polymorphism (or SNP)   This is a segment of DNA in which one of its original nucleotides has been naturally substituted for another. This variation may alter the function of DNA. SNPs are inherited. Each person carries millions of SNPs, making them unique from other people.

taste     One of the basic properties the body uses to sense its environment, especially foods, using receptors (taste buds) on the tongue (and some other organs).

trait     A characteristic feature of something. (in genetics) A quality or characteristic that can be inherited.