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The Ellen Payne Odom Genealogy Library Family Tree
The Family Tree - February/March 2003
DNA by Dr Knight

Genealogists are rapidly becoming aware that they now have a powerful new means of investigating the past - a system so powerful that genealogy will never be the same again.  It's been a long time coming, because without dramatic achievements in computer science and molecular biology, this new venue for genealogical research could never exist.

It all started at the beginning of the 20th century, when scientists began to realize our existence was controlled by chromosomes and something new called "genes."  The scientific observations were already reported by Mendel, but it took the emerging technologies of microscopy and the diligent efforts of biochemists to open up new vistas for the field of genetics.  While some diseases are inherited according to Mendel's laws, human inheritance patterns were found to be much more complex, or "multifactorial," in many others.  Clinicians became fascinated by "inborn errors of metabolism."

The rate of research on the body's building blocks, DNA, began to accelerate in mid-century with the development of the transistor, leading to impressive expansion of capabilities in data acquisition, storage and retrieval.  Watson and Crick described the alpha-helix and genetic research and engineering shifted rapidly into a higher gear.  As the century ended, the ambitious Human Genome Project met its first goals, but only because technology now made it possible, through on-line sequencing and databases, to perform and record detailed studies on genomes, transmitting the findings to anyone who was interested and had a computer.  Before we realized it, the genetic era has metamorphed into the genomic era.

Benefits for genealogists
Genealogists have benefited greatly from this information explosion in all aspects of their traditional research.  Critical research sources, such as census records, vital records, military and pension data and a vast variety of legal documents have become available on the web or recorded on electronic media.  Much research can be done successfully on a lap-top computer.  It has also been practical to "mind" large written databases for genealogical and related valuable medical information.  Inherited human genes offer a marvelous documentation of ancestry, potentially far more reliable than any previous oral or written source.

The result is that genealogy, traditionally a highly respected art, is now also a science.  A few genealogists don't realize this yet and have to be dragged, kicking and screaming, into the new millennium.  But most are impressed with the potentials this new approach offers.  Many are excited about the opportunities to solve long-standing genealogical mysteries.  They're anxious to use these new "tools of the trade," but they have questions, and rightly so.  Are genomic studies reliable?  Are they affordable?  What confidentiality protections are in place.  Once I have my DNA for study, who owns the data, who has access to the results, and who can use it for research?  And what are the best studies to perform for our own family's needs?

Y's and wherefores of parentage
At this early stage, two very different types of DNA analysis are being used to trace our ancestors.  One of these uses the Y chromosome, which is of particular value to genealogists because it is only transmitted by a male to his male offspring and Western culture, rightly or wrongly, has always placed more emphasis on the paternal pedigree.  Laboratories are offering comparative studies using various markers which they can identify on these Y chromosomes.

The Y chromosome of a son is not always identical to that of his father, as markers can change, or mutate, from one generation to the next.  Markers, or chromosomal changes occurring each generation, include idels: insertions or deletions of DNA; SNP's: unique event polymorphisms or rare single-nucleotide polymorphisms; microsatellites: usually of four nucleotides; and minisatellites; longer sequences of nucleotides. 

For example, the Y-specific minisatellite MSY-1, which has a mutation rate of a few percent per generation, can be studied along with less rapidly mutating systems (e.g., microsatellites with rare mutations per generation or extremely rare base substitutions per generation), used in the genealogical approach to Y diversity.  The slowly mutating markers define "haplogroups" of chromosomes related by descent and the microsatelliltes and minisatellite can then be used to study diversity.

Areas of the Y chromosome which mutate extremely slowly have been found to be characteristic of certain geographical areas.  Hapotype 1 is especially common in Western Europe and most of these males also have Haplotype 1.5.  Hapotype 2.47 and 3.65 are more common in Norway and other Scandinavian countries.  It appears that while their haplotypes remained stable, many males migrated.

Probabilities prevail
Haplotypes are comprised of paired genes, or alleles.  Testing these alleles helps to distinguish and separate large numbers of samples.  Bryan Sykes refers to the most common European groups as haplotype 1 and haplotype 2.  The DNA analysis is then done for microsatellites which mutate frequently and make up most of the chromosome.  Each microsatellite is assigned a number.  There is no uniformity as to how many of satellites are included in the analyses - it varies from laboratory to laboratory and is continually changing within laboratories.  If two samples share similar microsatellites, the statistics strongly favor a common ancestry.

Suppose these microsatellites are almost identical, e.g., 90 our of 100 match.  What does that imply?  One thing is certain: You have no idea from a single analysis just how long this "mutation" has been there.  Was it from a different parent's Y chromosomes or was it a chance random mutation?  You can get some idea by comparing the frequency in a control population. If the haplotype is very rare in the control population and is seen occasionally within a small, similarly-named group, it's likely that it was a mutation within the group rather than from an interloper.  Results of the haplotype analysis can be charted, linking microsatellite test results with their nearest neighbors, or those having similar or just one differing group.  These form a related haplotype node.  An example of how this methodology is used is the POMEROY-POMROY-POMERY-PUMMERY analysis in the Pomeroy Genetics Project #6.  This ongoing project also demonstrates the value of expanding the data base of participants in any study.

Related studies
We can benefit by checking the standards applied in paternity testing, which now uses genome testing to find or exclude parentage.  Paternity studies, which include both genetic and non-genetic evidence, calculates a statistical probability or paternity.  In most cases, a probability of parentage requires a minimum standard value of 99%.  Obviously, these standards established for credibility, must be valid for legal judgements, far exceed those usually required for genealogical "proofs."

Every month, new family studies appear in professional journals or on websites, attesting to the enthusiastic acceptance by genealogists of this new methodology for studying their past family histories.  It is of particular value in clarifying fuzzy relationships which just couldn't be resolved with any degree of certainty by usual genealogical methods.  But there are other useful applications.  Many major population migrations and interactions are also being clarified for the first time by Y chromosome research.

A recent study made a significant contribution concerning the diaspora of Jewish populations, starting in 586 BC, and connecting them to modern communities in both the Middle East and Europe.  The research by Dr. Michael F. Hammer of the University of Arizona, and his colleagues around the world, also showed that the Y chromosome links widely scattered Jewish communities with each other and with Palestinians, Syrians and Lebanese.  Dr. Hammer found 19 variations in the Y chromosome family tree which further subdivided the descendants from a single male estimated to have lived 140,000 years ago.

A work in progress
Genealogists should be aware that this whole field is a very new research and it is continually undergoing changes.  Do more markers mean more reliability?  At this stage, not necessarily.  We are dealing with raw figures, mapped and evaluated by computers which have to be programmed to access the importance of different findings, such as DNA mutations.  The exact rates of mutation are not necessarily known for every locus under investigation.  Also, there is a growing need to establish criteria which will require the same performance standards and provide similar statistically significant results from all participating laboratories.  This is the same scenario which took place among clinical laboratories when the College of American Pathologists developed quality assurance standards so that laboratory results from multiple institutions could be compared because they met similar criteria.  Of course, this also means agreement on a uniform nomenclature (or alphanumeric identification) so that we are all talking about the same genomic jargon!  Evaluation of marker validity is an ongoing process and we can expect many new markers in the future, plus more precise means of comparative evaluation.

Mitrochondrial DNA
Fortunately for women, the other most useful method for genealogists is mitrochondrial DNA, which originates in little power plants located outside of cell nuclei.  It differs from Y-chromosome DNA, which comes from within a cell's nucleus, and because this DNA doesn't have to go through the mitotic divisions of nuclear DNA, it gets transmitted directly from a mother to all of her offspring.  Only the female offspring can pass it along to their children, so it represents an excellent way of following the maternal, or "umbilical" line of inheritance.  Paternal DNA plays no role in offspring because almost all of it manages to be destroyed in the human ovum when it is fertilized by a sperm, although paternal "recombination" does occur regular in plants and some animals.

The first genetic studies traced maternal lines to a woman said to have lived in Africa about 200,000 years ago.  Mitrochondrial DNA has been sequenced since the 1980s, as its relatively small size made it far simpler than the massive effort required for nuclear DNA.  Dating estimates are based upon an assumption that rates of mtDNA mutation remained steady over all this time and that there was no recombination, or influence by paternal DNA during reproduction.  Although some questioned this concept, until recently most scientists agreed there was no paternal mtDNA in humans, but a case reported in 2002 by Schwartz and Vissing entitled "Brief report: paternal inheritance or mitrochondial DNA," described a patient with a rare muscular disease whose striated muscles contained only mutated paternal mtDNA. This seems to be a rare occurrence, but as with other DNA analyses, research is in its infancy on this and related matters.

Studying the Mitrochondrial genome
The mitrochondrial genome contains 13 protein-coding genes, 22 tRNA's and 2 rRNA's.  Studies have focused on polymorphisms in a small area of the Mitrochondrial genome called the D-loop, which comprises about 7 %  of the mtDNA genome.  Earlier studies concentrated on this area because of its high mutation rate, but this may have obscured some of the data.  New technology now permits study of the entire genome and is especially useful in the speciality that was called "population genetics" but is now "populations genomics."  More recent studies suggest that modern humans appeared in Africa 171,500 years ago, but the recent confirmation of paternal mtDNA influence may necessitate resetting of some Mitrochondrial clocks.

Human mtDNA sequences including HV1 and HV2 have been found useful, especially when samples are aged, severely degraded or of limited quantity.  Variations can be studied using sequence-specific oligonucleotide (SSO) probes or by denaturing high-performance liquid chromatography which targets the mtDNA control region or the entire mtDNA genome database.  Many human remains have been examined using mtDNA and it has been useful in samples as small as a single human hair.  It also has been able to show maternal linkage on forensic bone specimens.

A number of investigators have reported extensive studies on female mtDNA genetic trees, including Douglas Walles and associates at Emory University School of Medicine; Bryan Sykes at Oxford University; Dr. Cavalli-Sforza at the University of Padua; and William Goodwin at the University of Glasgow.  University-based molecular pathology laboratories combined to show that the mtDNA of the Kennewick man, found in the State of Washington, was unrelated to modern Native Americans.  The mysteries of the Iceman (found in an Alpine glacier) and Ice Maiden (from the Peruvian Andes) were also solved by mtDNA analyses.

Haplotype data bases are continually being improved, concentrating on geographical areas or attempting to link your family with various ethnic groups.  We can expect many innovations in this field and correlations among ethnic predispositions and various medical conditions may prove to be very useful to present and future families.  We strongly endorse collection and preservation of DNA from recently deceased persons, especially if they will be cremated, because so much valuable DNA information is now being lost forever - information which could help spare future generations from serious medical problems through early diagnosis, treatment or even prevention.

Unexpected, unwanted outcomes
Researchers in molecular biology have received enthusiastic support from many genealogists and others who are generousl generously making their DNA available for scientific studies, and some of the genomic findings have already rewritten history and heavily pruned some family trees, replacing fiction with facts.  Genomics is a two-edged sword, and the findings aren't always those that were expected, were desired, or ones that conform with current definitions of "politically correct."  Humans are prone to making mistakes and all levels of behavior, many of which reshaped some prominent family pedigrees.  Like George Washington, genomics may chop down the family's cherry tree, but unlike George, genomics can create new ones.  Many of these family trees have flourished, albeit under assumed names.  DNA fingerprinting is one of the more highly developed subspecialities of genomics.

Forensic and medical capabilities of DNA interpretations may have progressed farther than is generally appreciated by someone contributing a personal DNA sample to a group study that includes large numbers of total strangers with similar surnames. This tiny sample can provide a wealth of personal information and in the future, even more will become available.  Already, DNA can produce a genetic "photofit" which can determine hair color, eye color and ethnic appearance.  It can reveal the presence of or predisposition to an ever-increasing number of serious medical diseases involving every body system and predict the manner in which they can be transmitted to future generations.  Nuclear DNA abnormalities are most commonly associated with well-recognized disease patterns, as occur in various types of cancer, heart disease, diabetes, neurological and mental disorders, and diseases of specific organs.  Mitrochondrial DNA is trickier; because it's involved with providing energy through oxidative phosphorylation, its mutations play roles in diseases affecting organs which require much energy or it works in concert with nuclear DNA to cause complex disease syndromes.

This information can be very useful to a family which is attempting to recognize, treat or prevent a serious medical condition.  It also can have devastating psychological impacts which require genetic counselling, might affect insurability and have serious legal liabilities.

We are not questioning the motives of the now vast majority of university or commercial laboratories currently engaged in DNA research and analysis, but unfortunately, the paths genealogist are following are full of legal potholes.  The genealogist needs to understand the scope and the limitations of any signed "informed consent" and to realize that there is currently no uniformity in state laws controlling medical record confidentiality.  There are multiple other legal problems which involve DNA banking, care of DNA samples, limitations on research and dissemination of results, possible subpoena of DNA by courts, etc.  Retrieval of DNA samples from a distant central bank by a surviving relative could easily become a complicated matter.  There is need for uniformity and a single national policy concerning all these legal matters.

Right now, it's chaotic
Genealogical uses for DNA are not the primary ones, which remain in the fields of medicine and forensic science, but they are nevertheless very valuable and can provide answers to problems that could be solved in no other way.  Medical studies have already passed through the genetic phase and now involve genomic phases and post-genomic aspects.  We predict that genealogists will depend increasingly upon genomic data for verifying or disproving genealogical concepts.  Researching records may be more fun, but genomic research will be fascinating, too, if only because the outcomes, at least now, are reliable but so unpredictable.  Princes may become paupers; paupers may beget princes.  The rules of the games haven't changed - we'll just have to play by them more carefully from now on.

One last suggestion
One last suggestion: We are using an emerging technology which is continually improving. Improvements mean changes and changes lead to confusion.  Newly discovered loci and mutations will replace some of those in wide current use and the present ones may be assigned new names.  New methodology will also affect the reporting format.  And, as in the rest of the business world, there are always business failures and corporate mergers, so your favorite laboratory may suddenly disappear.  In order to protect all of the time, energy and expense your family has invested in genomic research, you might consider one more step.  When DNA samples are submitted, collect one more sample from each participant, but don't submit it.  Instead, have it preserved by lyophilization and establish your own private family DNA bank, available for unforeseen future needs.  You won't even have to refrigerate the preserved DNA, as room temperature storage will suffice.  Someday your family will be glad you saved those previous DNA samples when they were so readily available.

And, may the Genie of Genomic Genealogy smile upon your family!

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