Medical & Genealogy

There are essentially two main uses for DNA from both an ancestry and from a medical insights perspective.

Ancestry lets you explore your heritage and ancestry through a variety of tests. You can look back several generations with STR test, Tens of generations with the SNP tests and thousands of years with your mitochondrial DNA tests.

Medically speaking, DNA is playing an increasingly important role in predicting hereditary diseases and ‘personalized’ or ‘precision’ medicine.

Hereditary disease prediction is possible through building your family’s Generational DNA Library.  Doctors and scientists are able to analyze DNA gene mutations from one generation to the next.  This results in the capability to predict not only IF a family member will be diagnosed with a hereditary disease, but approximately WHEN the hereditary condition will be triggered.  This leads to early identification and early treatment.

On the extreme, what we are talking about here is saving lives.  And at a minimum, DNA is very capable of minimizing invasive treatment plans (chemotherapy, surgery).

Ideally, every family member will have their own DNA vial securing a powerful spot in the Family Biological Tree.

READ ABOUT SOME REAL LIFE STORIES

Ancestry SNP

DNA is passed from parent to child, so you inherit your SNPs versions from your parents. You will be a match with your siblings, grandparents, aunts, uncles, and cousins at many of these SNPs. But you will have far fewer matches with people to whom you are only distantly related. The number of SNPs where you match another person can therefore be used to tell how closely related you are. This type of ancestry tests vary in their ability but are generally thought to be able to see approximately 10 generations back in history. That relates to approximately 450 to 500 years ago.

Many people relate their ancestry to a particular country like Italy or France but in reality those are political entities with shifting borders and influxes of different genetic populations over history.  Within a country like Italy for example Northern Italians will have a lot of variation from Southern Italians and most populations now will be a mixture of European, Asian and or African as different populations moved around and intermingled.

Ancestry Y

Single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.

SNPs occur normally throughout a person’s DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function.

Most SNPs have no effect on health or development. Some of these genetic differences, however, have proven to be very important in the study of human health. Researchers have found SNPs that may help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases. SNPs can also be used to track the inheritance of disease genes within families. Future studies will work to identify SNPs associated with complex diseases such as heart disease, diabetes, and cancer.

Y-DNA testing looks at the DNA in the Y-chromosome, a sex chromosome that is responsible for maleness. All males have one Y-chromosome in each cell and copies are passed down (virtually) unchanged from father to son each generation.

Used For:
Y-DNA tests can be used to test your direct paternal lineage – your father, your father’s father, your father’s father’s father, etc. Along this direct paternal line, Y-DNA can be used to verify whether two individuals are descendants from the same distant paternal ancestor, as well as potentially find connections to others who are linked to your paternal lineage.

Available To:  
Males only. Y-DNA tests specific markers on the Y-chromosome of your DNA known as Short Tandem Repeat, or STR markers. Because females do not carry the Y-chromosome, the Y-DNA test can only be used by males.

A female can have their father or paternal grandfather tested. If that is not an option, look for a brother, uncle, cousin, or other direct male descendant of the male line you’re interested in testing.

Y-DNA TESTING  (STR)

When you take a Y-line DNA test, your results will return both a general haplogroup, and a string of numbers. These numbers represent the repeats (repeats) found for each of the tested markers on the Y chromosome. The specific set of results from the tested STR markers determines your Y-DNA haplotype, a unique genetic code for your paternal ancestral line. Your haplotype will be the same as, or extremely similar to, all of the males who have come before you on your paternal line — your father, grandfather, great-grandfather, etc.

Y-DNA results have no real meaning when taken on their own. The value comes in comparing your specific results, or haplotype, with other individuals to whom you think you are related to see how many of your markers match. Matching numbers at most or all of the tested markers can indicate a shared ancestor.

Depending upon the number of exact matches, and the number of markers tested, you can also determine approximately how recently this common ancestor was likely to have lived (within 5 generations, 16 generations, etc.).

Ancestry Mitochondria

Mitochondrial DNA (mtDNA)

The power houses for the cell have their own DNA that is separate from the nuclear DNA inside the cell. This DNA is very small and only codes for products of the mitochondria. Due to the small genome size there is little room for mutation that doesn’t result in death this DNA passes virtually unchanged from mother to children over generations.

Shortly after the process of fertilization, the sperms’ mitochondria die away, and the embryo is only left with maternal mitochondria. As such, we share the same mtDNA as our brothers and sisters, but not our fathers.

MtDNA is also passed down nearly unchanged from generation to generation. So we share the same mtDNA-type as our mother, our maternal grandmother, our maternal great-grandmother and so on. In fact the exact same mtDNA code will track our direct genetic line back until the point at which a natural mutation in the mtDNA code occurred – on average about every 20,000 years.

The area which can accumulate mutations is called the D loop and by analyzing this area shared mutations will show ancestral heritage as far back as 20 000 years ago. The mitochondrial DNA test will indicate a Haplo group which will be shared by people from different regions of the world indicating where you’re original, ancestors came from.

Genetic Predispostion

Single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.

SNPs occur normally throughout a person’s DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function.

Most SNPs have no effect on health or development. Some of these genetic differences, however, have proven to be very important in the study of human health. Researchers have found SNPs that may help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases. SNPs can also be used to track the inheritance of disease genes within families. SNPs are also associated with complex diseases such as heart disease, diabetes, and cancer.

By screening the SNPs a comprehensive report is generated which indicates if the mutations are present and the risk factor by having the accumulated mutations. Generally they are reported as low, medium and high for example diabetes. A high risk indication should prompt consultations with a Doctor and lifestyle changes as the accumulated mutations make you at risk of developing the disease even when living a moderate lifestyle which most people wouldn’t develop diabetes from.  Hereditary cancers and diseases are also indicated which is helpful in looking at your families health and lifestyle.

Personalized Medicine

Personalized medicine is the tailoring of medical treatment to the individual characteristics of each patient. The approach relies on scientific breakthroughs in our understanding of how a person’s unique molecular and genetic profile makes them susceptible to certain diseases. This same research is increasing our ability to predict which medical treatments will be safe and effective for each patient, and which ones will not be. Personalized medicine may be considered an extension of traditional approaches to understanding and treating disease. Equipped with tools that are more precise, physicians can select a therapy or treatment protocol based on a patient’s molecular profile that may not only minimize harmful side effects and ensure a more successful outcome, but can also help contain costs compared with a “trial-and-error” approach to disease treatment. Personalized medicine has the potential to change the way we think about, identify and manage health problems. It is already having an exciting impact on both clinical research and patient care, and this impact will grow as our understanding and technologies improve.

Real Life Example

VANCOUVER — Trish Keating’s cancer was a particularly vicious breed of monster.

Her colorectal cancer diagnosis in 2010 was followed by a repeating cycle of surgeries, chemotherapy, and radiation and, when she and her doctors thought they had finally slain the beast, relapses.

Keating, who worked as costume designer in the film industry, was told in late 2013 that the cancer had returned once again and this time it was terminal. She might have two or three years to live.

Trish Keating, who successfully underwent an experimental colon cancer treatment with a drug commonly used to treat high blood pressure.

Last fall, Keating, 67, joined a clinical trial in Vancouver that sequenced her genome. She was put on a drug typically used to treat high blood pressure and within five weeks the cancer was barely detectable.

“When you’ve lived with cancer for five years and you’re trying to beat the dragon that’s breathing behind you, when finally someone says to you ‘We can’t see any (cancer)’, first of all you’re incredulous, kind of in a state of shock,” Keating said in an interview.

“It takes a while. It took me and my husband a couple of days for that to set in.”

Keating’s doctor treated her as part of a B.C. Cancer Agency study into personalized onco-genomics, or POG — an experimental method of examining tumours to identify potential treatment.

While the technique could be years away from widespread clinical use, the researchers hope it could one day allow doctors to customize treatments to each patients’ individual tumours and improve their odds of survival.

Dr. Howard Lim said that in Keating’s case, the genomic sequencing identified a specific protein as the driving force behind her cancer. His team identified an existing blood-pressure medication known to block pathways to that protein.

Generational Library

Building what is known as a generational DNA library is incredibly important. Saving not only the DNA of yourself but of as many direct family members as possible. This allows doctors right now to be able to identify the mutations in a families DNA which are causing disease. There are millions of mutations within a person which do not cause disease and seem to be neutral to a person’s health. When the number or location of the mutations do cause disease it is very difficult to identify in a constantly changing sea of mutations.

DNA sequences are passed with very little variation from one generation to the next; therefore the DNA of a 95 year old great-grandmother is of immediate and direct relevance to the health of her six month great-grandson. Approximately 75% of all diseases are now traced back to genetics. As knowledge of genetic medicine increases, a more complete familial genetic history is of very high importance-most hospitals now have integrated DNA testing as part of their common practice. The determination of the medical condition itself, the efficacy of potential therapeutic agents, as well as the risks and sensitivity of the patient to treatment, is greatly enhanced by a complete genetic family history. Without this vital information, pinpointing the exact defective cell mutations is like trying to find a needle in a haystack.  Preserving DNA and having access to your family’s genetic history is very important in accurately guiding the medical profession to pinpoint, track, diagnose and prevent everything from simple skin disorders to terminal cancer.

The more familial DNA that is preserved, the more doctors have to work with in predictive and precision genomic medicine. Having direct family members who share a lot of the same DNA lets doctors compare sections to see where mutations are accumulating and what the mutations are. This becomes a very powerful tool as it can actually let doctors not only predict if a person is going to get a disease but approximately when.

Your family’s genetic legacy is invaluable and needs to be preserved.

Gene Therapies (CRISPR)

Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.

The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short”guide” sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Although Cas9 is the enzyme that is used most often, other enzymes (for example Cpf1) can also be used. Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

Genome editing is of great interest in the prevention and treatment of human diseases.. It is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosishemophilia, and sickle cell disease. It also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection. There are successful treatments of individuals and in the next while these techniques will be available to patients.

Diagnose and Treat Disease

People use genetic testing for several reasons. Prospective parents may want to be tested for genetic mutations that could cause genetic diseases in their children. Before prescribing certain drugs, physicians use tests to predict how a patient will metabolize that medication and whether that patient is likely to experience serious side effects. In the case of certain cancers, oncologists can test to know which therapies may be most effective for a particular patient. People with genetic diseases in their family history may benefit from knowing their likelihood of inheriting that disease. Testing DNA is a useful diagnostic tool in treating children who develop serious conditions that defy diagnosis.

The benefits of health genetic testing can generally be divided into three areas:

  • Tests that help a person anticipate conditions for which they or their offspring may be at risk.
  • Tests that help a patient and his or her physician decide on the best course of treatment for a particular condition.
  • Diagnosing diseases

Since genomic research is very new, definitive benefits are a source of great debate and opinion. A test such as the one that identifies the BRCA1 and 2 mutations for breast and ovarian cancer is universally considered of great predictive value, and patients who test positive are urged to consider prophylactic measures. Another useful test for cancer risk is the one for hereditary nonpolyposis colorectal cancer (Lynch Syndrome).

Other tests, especially those that identify predisposition to chronic diseases such as diabetes or hypertension, are considered far less predictive. Patients who test positive for these genes will likely be counseled to make the healthy lifestyle choices they have already been urged to make by their physicians.

Genetic testing looks for specific inherited changes (mutations) in a person’s chromosomes, genes, or proteins. Genetic mutations can have harmful, beneficial, neutral (no effect), or uncertain effects on health. Mutations that are harmful may increase a person’s chance, or risk, of developing a disease such as cancer. Overall, inherited mutations are thought to play a role in about 5 to 10 percent of all cancers. So only certain changes in DNA will have an effect. There in lies the challenge to identify which changes are diseases causing in a background of constantly changing DNA sequences over a lifetime.  Taking a babies DNA at birth can provide a master copy later in life that will not have all the environmental changes and strictly the inherited DNA mutations.

Cancer can sometimes appear to “run in families” even if it is not caused by an inherited mutation. For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. However, certain patterns—such as the types of cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer typically develops—may suggest the presence of a hereditary cancer syndrome.

The genetic mutations that cause many of the known hereditary cancer syndromes have been identified, and genetic testing can confirm whether a condition is, indeed, the result of an inherited syndrome. Genetic testing is also done to determine whether family members without obvious illness have inherited the same mutation as a family member who is known to carry a cancer-associated mutation.

Inherited genetic mutations can increase a person’s risk of developing cancer through a variety of mechanisms, depending on the function of the gene. Mutations in genes that control cell growth and the repair of damaged DNA are particularly likely to be associated with increased cancer risk.

No. Even if a cancer-predisposing mutation is present in a family, it does not necessarily mean that everyone who inherits the mutation will develop cancer. Several factors influence the outcome in a given person with the mutation.

One factor is the pattern of inheritance of the cancer syndrome. To understand how hereditary cancer syndromes may be inherited, it is helpful to keep in mind that every person has two copies of most genes, with one copy inherited from each parent. Most mutations involved in hereditary cancer syndromes are inherited in one of two main patterns: autosomal dominant and autosomal recessive.

So not all diseases are genetic based and may be environmental but without a genetic history of the families involved it will be impossible to know.  As all the mechanisms involved are also not understood having the genetic record of a family will allow doctors to test for several genes in a family history which may be having a synergistic effect for developing diseases such as cancer. Also in patients who have already been diagnosed with cancer, a positive result for a mutation associated with certain hereditary cancer syndromes can influence how the cancer is treated. For example, some hereditary cancer disorders interfere with the body’s ability to repair damage that occurs to cellular DNA. If someone with one of these conditions receives a standard dose of radiation or chemotherapy to treat their cancer, they may experience severe, potentially life-threatening treatment side effects. Knowing about the genetic disorder before treatment begins allows doctors to modify the treatment and reduce the severity of the side effects.

Although cancer is often used as the example for genetic testing the same principles apply for many other diseases especially ones which don’t have an immediate discernable cause like many neurological and immunological diseases. Currently, for the patients and their loved ones, one of the most difficult aspects is getting to the right diagnosis. For many families, the diagnostic odyssey lasts years and even decades. Families trek all over the world seeking answers, looking to connect to the right specialists that can give them more clues, and directions for their diseases. Often, not knowing what is wrong is one of the hardest challenges. The right diagnosis is the first foundational step that sets into motion all subsequent plans to help the patient. As there are still a lot of variations to consider, additional filtering strategies are important to isolate the possible gene or genes that are causing the illness. Since parents share 50% of the genetic makeup with their children, their genomes serve as a good filter. If both parents are normal, you can remove all the variations that are also present in the parents. If either of the parents is affected, we can look at what is shared between the people affected by the disease. This step helps filter the thousands of possible differences to tens of possible outcomes which helps diagnosis. Having a grandparents DNA as a filter can narrow it down even more.  Great grandparents even more.

Prevent Disease

Healthy people have been intrigued by the possibility that genetic testing may tell them more about what the future may hold and then using that knowledge improve their health.

DNA has become an extremely useful tool for predicting disease. By allowing medical professionals to identify genes in DNA that are markers for disease, a person can make appropriate lifestyle or similar modifications to help lower the risk of disease. For those diseases that are inherited, identifying a parent who is a carrier but does not express the disease can also help parents make informed choices regarding a potential pregnancy.

The Future

DNA understanding is still in its infancy.  As of now only 5% of the DNA has a positively identified function. Meaning 5% of the genome is what codes for all the genes express as traits like hair color or height. 95% of the DNA has until recently been labeled as junk but new research is showing that it definitely has a regulatory function.

This can help explain why certain genetic traits like breast cancer mutations may be present but fail to cause the disease over a person’s lifetime.

There are indications that DNA may have behavioral and possibly memory implications. The instinctive behavior seen in animals could indicate that information is passed genetically from parent to offspring.

Twin studies of identical twins also show unexplainable behaviors shared by both when they have never met and we raised in totally separate environments.

The future of DNA is very exciting as we begin to unravel the code and understand the complex interactions the create life. The reason we age and die is because our DNA becomes damaged over time. Our repair mechanisms inside our body eventually break down and errors begin to accumulate.

A 90 year old woman’s body is only 2 years old. Your blood is replaced every few months and your bones every few years it’s just that it is being replaced with the damaged copies. As we understand DNA we will be able to extend life and cure most diseases. The future looks very exciting but DNA must be preserved as it begins to degrade as soon as the bodies repair systems stop maintaining it.