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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! |
