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Genetics
On Genetics and
Genealogy, Part I As
some of you may know, I am a physician working in the field of
genetic diseases at St. Louis University. As I have become more
familiar with the methods of family history, I have been struck
by the many overlapping issues between the fields of genetics
and genealogy. I would like to use this column to begin to
describe some of them. First, just how related are we? Can
modern molecular biology distinguish the fact that many of us
are 8th , 9th or 10th cousins? Are two of us who might be
Brewster cousins, for example, really any more related than any
other two ethnically similar people? The answer is complicated,
but an estimate may be made from the frequency of genetic
diseases in our population. Among American Caucasians, the rate
of diseases which result from inheriting the same mutated gene
from both of your parents (a monogenic disease) has been
estimated to be about 1% of all births1. This means
that there is a fairly high background of inbreeding in our
population. To illustrate this, we all know that most states
forbid, for public health reasons, the marriage of first
cousins. The risk of having a child with a monogenic disease for
first cousins can be calculated and is about 6%, for second
cousins 1.6%, and third cousins 0.8%2. Thus the
general population, marrying at random, has about the same
"inbreeding" risk as second- to-third cousins. Another way to
think of this, more familiar to genealogists, is to estimate how
many ancestors we all have in common. If you have 4
grandparents, 8 great-grandparents, etc., back x generations you
have 2x grandparents. How many generations back do you have to
go before you have a number of grandparents equal to the total
population at the time? The population of the world 1000 years
ago has been estimated at 250,000,000, and the population of
Western Europe about one-tenth of that, 225 equals over 33
million, so if a generation is 20-40 years, only 25 generations
ago, if there were no inbreeding, your ancestors would be every
single Caucasian who has descendants. It is no exaggeration to
say that it is likely that every person of Northern European
descent is a descendant of Charlemagne, and assuming they had
descendants who survive to this day, Joe the Baker and his wife,
Kitty. Likewise, if Joe and Kitty lived 1000 years ago, and had
only two kids, who each had two kids, who in turn over the
centuries have had only two kids in orderly 30-year generations,
the entire population today would be their descendants (actually
over 8.5 billion descendants). When you average out all these
effects, we all turn out to be about as similar as third
cousins. This is not to say we are not all unique. We all have
two copies each of about 80,000 genes, and for each one of us,
probably about 20% of those genes have one copy that is "mutant"
3. Another way of looking at this is that one letter out
of about 500 in our genetic code is probably a mutation, for a
total of about 160,000 mutations per person4. Most of
these mutations make no difference at all, but are useful for
DNA identification techniques. Current molecular biological
methods can follow patterns of these mutations through families
and determine descent with a high degree of certainty.
Incidently, according to experts in the field, paternity does
not match what would be surmised from civil records in about 10%
of cases. Yet for all their power, no DNA identification scheme
today can deduce the most common physical traits of the person
whose DNA is being analyzed--not their height, weight, skin
color, hair or eye color. In the next Missouri Compact: how your
maternal (mitochondrial) or paternal (Y chromosome) ancestry
could be proven, once and for all. 1. Scriver, CR, et
al, The Metabolic and Molecular Basis of Inherited Disease, 7th
Edition, p.66. 2. Hartl, D, A
Primer of Population Genetics, 2nd Ed, p. 58 3. #1, above, p.64
4. #1, above, p.
65 On Genetics and
Genealogy, Part II I
am sure everyone has heard something about
tracing genealogical lines through the study of mitochondria
[might-oh-con'-dree-ah] or Y chromosomes. The infamous cases of
Jesse James and Thomas Jefferson, respectively, depended on
studies of these biological materials. The study of mitochondria
for lineage analysis rests on the principle that we receive
these only from our mothers whereas the Y chromosome is carried
only by males and passed only to their sons. Mitochondria are
"organelles": that is, they are to each cell of the body what an
organ is to the body as a whole. The functions of the
mitochondria are many and include the production of energy, the
burning of fats, and the disposal of nitrogen. Mitochondria have
their own genes, distinct from the genes of the cell found in
the cell's nucleus. This plus other factors leads us to believe
that the mitochondria are remnants of bacteria that developed a
live-in relationship with early one-celled creatures. Each human
egg contains up to 1000 mitochondria and these can include
several different sets of mitochondrial genes. Since each of us
develops from a single egg, and we get no mitochondria from the
father's sperm cell, the mother's mitochondrial get distributed
throughout our various body organs as we grow in the womb. This
makes the study of mitochondrial genetic mutations especially
difficult--each person may have normal mitochondria in some
tissues and mutations in others--but one thing is certain, they
all came from your mother. To a genealogist,
the significance of this is that your mitochondrial genes are a
"shortcut" back through your all-maternal line to the origin of
that line. The Armed Forces Institute of Pathology, which has
the grim task of identifying the remains of US soldiers, has
exploited this fact by classifying mitochondrial genetic
patterns according to their region or ethnic group of origin.
Thus, from a small sample of tissue such as bone or teeth the
mitochondrial genes can tell whether the source was Native
American, African-American, Northern European or whatever. By
studying the variations in the mitochondrial DNA from around the
world, and by knowing or estimating the rate of variation (how
often mutations are introduced), it has been possible to
estimate the age of the human species. This is the so-called
"Eve" hypothesis that places the origin of our species in
Sub-Saharan Africa about 200,000 years ago. The Y chromosome's
burden of mutations seems to be much lighter. Similar regional
and ethnic studies of the Y chromosome have shown virtually no
mutations in the functioning parts of the genes, and only a
relatively small amount of variation in the nonsense or
space-filling parts of the genes. In the case of Thomas
Jefferson's male descendants, it was the discovery of a rare and
unusual mutation in the Y chromosome that made it possible to
compare candidate descendants to known ones. Of course, these
genes may have been carried through Jefferson's male cousins or
nephews. The
implications of recent knowledge about the distribution of
mitochondrial and Y chromosome variations has led to the
somewhat self-evident historical hypothesis that whereas women
tended to stay at home, men tended to roam. So the picture
derived from study of those alive today shows remarkable
homogeneity of the Y chromosome, as if we are all descended from
a few aggressive males who roamed the pre-historic world in
search of conquest. Actually, this is probably not true1.
The reasons that all ethnic groups have very similar Y
chromosomes may actually have to do with properties intrinsic to
the functions of the proteins encoded by the genes on the
chromosome. The best mathematical estimates of the age and
heritage of our species based on Y chromosome analysis suggests
an age around 188,000 years, roughly similar to the age based on
mitochondrial studies, and also seems most compatible and an
effective ancient human population size of 10,000 with equal
numbers of males and females contributing to the genetic
diversity1. There have been many recent scientific publications
detailing evidence on the origins of the Native Americans based
on Y chromosome analysis, with the most definitive placing the
ethnic group of origin in central Siberia about 40,000 years
ago.2 All of these
conclusions are based on the simple idea that mutations happen
in the course of the reproductive process and that if the
mutations don't render the offspring sterile, they are passed
down through the generations unchanged. So the mutations in
genes that all animals have, like the mitochondrial ones, carry
the record of every mutation that ever happened in the descent
of the creature being studied. Some of you may have seen the
billboards along Highway 40 in St. Louis offering a prize of
$250,000 to anyone who can "prove" the theory of evolution.
Certainly there has been much in the press about limiting the
teaching of evolution in Kansas and elsewhere. This sort of
debate would not need to occur if more people were aware that
each of us carries in every cell of our bodies the written
evidence, in our own genetic codes, of the origins of our
traits, our ethnic group and our species and our exact temporal
relationship to those species who were our progenitors. It would
make a great deal more sense and be a more interesting
proposition to offer $250,000 to anyone who could find a genetic
sequence in anything now alive or that ever lived that
contradicts the general evolutionary scheme hypothesized by
Darwin and his intellectual descendants. Of course, the way
science is funded in this country, it would have to be paid in
advance. In the next article, we will examine how familial
traits can be passed on without the involvement of genes due to
maternal or paternal "imprinting". 1. Hammer MF A
recent common ancestry for human Y chromosomes. Nature, Nov 23,
1995, 378(6555) p.376-8. 2. Santos FR The
central Siberian origin for native American Y chromosomes. Am J.
Hum Genet 1999, Feb, 64(2) p. 619-28. On Genetics and
Genealogy, Part III Everybody
has probably wondered at some time how family resemblances are
passed from one generation to the next. This is one of the
"payoffs" of genealogical research, especially for adoptees,
when the researcher finally meets relatives who, one way or
another, just look like family. There are many imponderable
surprises in raising your own family, and one of them has to be
the recognition in one's children of impossibly obscure traits
you are sure you have completely hidden all your adult life.
People report that their offspring have exactly the same taste
in clothes they had as children, or the same habit of doodling
pictures of the sun during class, or the same attitude towards
playing tag--traits you would assume are not due to "genes" but
cannot plausibly be due to teaching or role-modeling either,
since we are never children in front of our children. Of course,
when we speak of family resemblances, there is always the
recognition of Uncle Bob's nose or Aunt Minnie's telephone voice
in someone in the next generation. How are these traits
transmitted? Probably not always through the "genes" as we
normally think of them. The central dogma
of current biology is that genes are segments of DNA made up of
4 "letters" (adenine, guanine, cytosine and thymine) arrayed in
sets of three that specify the order of the 20 amino acids in
proteins; that the order of amino acids specifies, in a way that
is so complex no current computer can completely calculate it,
the shape and chemical function and of the proteins; that the
shape and chemical properties of proteins, along with the order
in which they are made, somehow determines the life and death of
cells, the cellular structure of the organs and everything about
us. But do scientists
really believe there is a bulbous-nose gene? Or a squeaky voice
gene? Or a set of genes that makes you smirk or snort in a
certain recognizable way after a joke even if you were raised
apart from your biological family who recognizes it? Recent
discoveries of genes governing the propensity for alcoholism,
risk-taking, shyness, obesity and other complex behaviors reveal
they are not simple Mendelian traits, but only genes that, if
you have them, increase your likelihood of developing the traits
involved. They are not as simple as Gene A makes you rude and
Gene B makes you polite. Even traits like eye-color and height
and risk for diabetes, cancer and heart disease are usually
inherited in a complex way, and not an all-or-nothing way. This
is due to the fact that the protein product of every gene must
interact with all the other gene products and that essential
life functions are ensured by redundancy, back-up plans and
compensatory mechanisms, just like the Space Shuttle. But there is now
the realization that everything in genetics is not due to the
simple A-G-C-T alphabet of the genetic code. The first proof of
this was in the area of genetic imprinting. It has now been
shown that inheritance of some traits depends on which parent
you got the gene from. Classical genetics always assumed that
maternal and paternal genes had the same chance of influencing
body type. Indeed, this was the whole biological point of sexual
reproduction, that the "superior" copy of a gene from either
parent would dominate in the offspring, yielding an offspring
potentially stronger than either parent. However, there are now
several genes known that are suppressed when inherited from the
father or mother by a process involving a chemical change called
methylation to the letter "C" in the genetic code. This results
in full expression of the copy of the gene derived from the
other parent, with no chance of compensation or correction. In
short, some genetic traits are not due to the lack of the gene
itself, but due to lack of translation of that gene into
protein. It has been
hypothesized that physical traits such as facial features may
not be the result solely of genes themselves, but from the way
the chromosomes unfold during the developmental process. Imagine
cells of the face as having facets like a diamond or a geodesic
dome. From which facet will a cell bleb off its daughter cells?
The ultimate shape of the face will be determined by the
direction in which cell division proceeds. This is probably
neither completely random nor controlled by genes or gene
products, but rather by the way in which the chromosomes are
coiled up and oriented as cells divide, then uncoiled as the
genes are transcribed into proteins. In other words, the exact
shape of an eyelid or nostril may be due to a very complex dance
choreographed not by the genetic code but by the coiling
architecture of the DNA and the way it is packed into the
nucleus of cells. Since chromosomes must make exact copies of
themselves using themselves as templates, you can imagine how
this shape might be passed from one generation to the next
without the involvement of the genetic alphabet itself. This helps to
explain why so little of the total DNA is actually comprised of
genes that have protein products. The rest has been regarded as
"spacers" or "deadwood", but may actually be crucial to the
passing on of the shape of the chromosomes that ultimately
determine some aspects of our own shapes. On Genetics and
Genealogy, Part IV This
is the fourth in a series of articles for Missouri Compact on
some of the issues that overlap between the modern field of
genetics and genealogy. The methods of genealogy have been
changing rapidly over the last several years with each new
technology, the microfiche, the CD-ROM, the Internet, the GEDCOM
file and personal computer-based genealogical software.
Similarly, even since this column began, when I first became
Governor of the Missouri Society two years ago, there has been a
dramatic change in the impact of genetics upon genealogy. The
most impressive change is that the type of genetic testing
mentioned in the second article in the series, mitochondrial DNA
analysis for tracing the maternal line, is now commercially
available from of a service of Oxford University in England, the
Oxford Ancestor Project. Here are their instructions taken from
their Internet WebSite: http://www.oxfordancestors.com/ Step 1. Send an
email to eve@oxfordancestors.com with your full return postal
address and the number of tests required. SEND NO MONEY AT THIS
STAGE. We mail you a DNA sampling kit with full instructions.
This contains the small brush used to collect cells from your
inner cheek easily and painlessly. Step 2. Return the
DNA brush with your payment cheque. We confirm receipt by email.
Your cheque will not be banked until your results have been
mailed back to you. Expect delivery within 28 days of our
receipt of your sample. So what do you get
for the $180 you send along with brushings from your inner
cheek? You get to find out which of the "Seven Daughters of Eve"
you descended from. The Oxford group has determined that 99% of
people of European descent can be classified as having come from
one of seven original "founder" females of Europe: Ursula, Tara,
Helena, Katrine, Velda, Jasmine or Xenia. These 7 are among 18
worldwide mitochodrial DNA types so far identified. These are
fictional names assigned to each of 7 areas of Europe: The geographic
distribution of Ursula appears to follow the use of stone tools,
Ursula's clan members drifted across all of Europe. The clan of
Tara settled in Tuscany 17,000 years ago. Descendants moved
across northern Europe and crossed the English Channel. Helena's
clan lived in the Pyrenees. As the climate warmed 12,000 years
ago, Helena's descendants traveled northward to what is now
England. Members of this group are now present in all European
countries. Katrine originated in Venice 10,000 years ago. Most
of Katrine's descendants now live in the Alps. Velda was
originally from Spain 17,000 years ago. Velda is now associated
with northern Finland and Norway. Jasmine's people were from
Syria, where they farmed wheat and raised domestic animals.
Jasmine's descendants traveled throughout Europe, spreading
their agricultural innovations with them. Less is known about
the most remote matriarch, Xenia, but it is believed that her
people lived in the Caucasus Mountains 25,000 years ago. Just
before the Ice Age, this clan spread across Europe, and even
reached the Americas. In a few months, the Oxford Ancestor
Project promises to have a commercial version of its Y
chromosome (male lineage) analysis available as well.
I raise the next
topic with trepidation, but with confidence that today's
Mayflower Descendants are sophisticated enough to accept it. It
is the concept of "good breeding". I have confidence in the
tolerance of our members to the idea that "good breeding" may
not promise everything our grandparents might have hoped,
because in the Missouri Society, just a few years ago, we
changed our Constitution and Bylaws to say that anyone who can
prove lineal descent from a Mayflower Passenger may become a
member regardless of their "acceptability", social, or
otherwise. This reflects modern thinking that just because one's
parents and grandparents were good people, it is no guarantee of
one's character, and conversely, if your ancestors were lowlife
red-necks, you might have the social graces of royalty. The
observation of history confirms that greatness is rarely
transmitted intact to succeeding generations, whereas great
talent can arise, seemingly out of nowhere, in families of the
most undistinguished sort. What are the genetic facts behind
these unsettling realities? First, each of us
carries within us a "shadow person": a complete set of human
genes that are, to an extent, suppressed or dominated by a
"superior" set of genes. We have two copies of each of our 23
chromosomes, and most of the time, even potentially fatal
mutations in one copy can be masked by the other copy. However,
the biological process of creating our children separates these
two copies from each other, and since the time of Mendel it has
been apparent that the "shadow" traits have just as good a
chance of being passed on as the dominant ones seen in the
parents, although if the traits go unseen in the parents, they
will probably go unseen in the offspring unless the chosen
spouse has the same hidden traits. Unfortunately, if you choose
a spouse from within your historically exclusive social class
and geographic area, you are just increasing the chances of
revealing the weak, suppressed genes of your "breeding group". Another biological
fact restricts the likelihood of seeing your own finer qualities
in your children: the chromosomes we pass on are those of our
parents and not our own. Of course, we carry the genes of our
parents, but these genes are arrayed in linked sets called
chromosomes. The 23 chromosomes in our eggs or sperm are in
place while we are still embryos, and the viability of those
chromosomes, including the "shadow traits" they may possess, are
as yet untested in life. Through the process of meiosis, the egg
or sperm that creates your child recombines the genes of your
two parents into single chromosome copies. This is the first
time that the best (or worst) traits of your mother and father
have the chance to be physically linked and potentially amplify
each other's weaknesses or play to each other's strengths in the
formation of an individual. For better or worse, these
recombined traits will have to compete with those of your
in-laws for expression. This is nature's way of ensuring an
element of surprise in the most carefully arranged marriages.
Talents such as verbal or musical ability, or personal
mannerisms may be due to the action of many genes acting
together, including genes from many different chromosomes. The
ultimate result is: the endearing traits of one of your parents
that appeared in you by the mechanism of gene dominance may
re-appear in your children by the mechanism of meiotic
recombination, but may be broken up again in succeeding
generations, never to reappear. On a final topic,
every genealogist has had to endure the tiresome jokes of the
form, "Well, there is a perfectly good reason why my kids are
like they are, half their ancestors were men/women!" (Choose
your own gender to blame). This statistical estimate that
exactly half your ancestors are of one sex and half are the
other may not be precisely true, as known to most family
researchers. It is possible to have an excess of one gender or
the other if you are descended from two or more children of an
ancestor through two or more spouses. For example, if you have
Francis Eaton as an ancestor through both his wives, Sarah and
Christian Penn, you have a male ancestor deficit and an excess
of females. If, however, you are descended from Christian Penn
(the second wife above) through both her husbands, Francis
Billington and Francis Eaton, you have a deficit of female
ancestors and an excess of males. I will leave it to the reader
to decide which is preferable.
Updated:
June 06, 2011
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