23andMe’s genetic health reports cover 191 rare genetic mutations in addition to more common variants related to disease. While it’s relatively easy to learn about common variants, our knowledge of rare mutations traditionally has come from very small studies limited to specific populations, like French Canadians living in Quebec or people with Ashkenazi Jewish ancestry. 23andMe’s 180,000+ customers, however, provide a unique opportunity to learn about these mutations in a more general population.
Within a large group of 23andMe customers who have consented to participate in research, we see that most of these mutations are indeed most common in the populations that have already been studied, but some are showing up in people whose ancestries have not been linked to that mutation before. I presented data about these mutations in a poster at the annual meeting of the American Society of Human Genetics (ASHG) last week in San Francisco.
Why might these mutations appear in people with ancestries other than those that have been studied? Perhaps our definitions of ancestry aren’t thorough enough and these people do actually have some of the expected ancestry. But it’s also possible that some mutations are present in these other populations and this is simply the first time researchers have documented it.
This second possibility has far-reaching implications. Couples planning to have children are often screened for genetic mutations that could cause inherited diseases in their children. Typically, they are screened for specific mutations thought to be most common in their ancestral group. Our data shows that many mutations can occur in people outside those ancestral groups. Add to that the fact that many people might not know all the details of their ancestry and the argument for broader screening becomes stronger.
Although it is clear that more research is needed, these observations may be an important first step towards better understanding who may be affected by rare genetic mutations.
When I went for my yearly mamogram yesterday, the Shaw Medical Center (in Colorado-oncology) asked if I were at all Ashkenazi genetically as part of their usual check in procedure. Is this an example of your observations?
Have not been asked that before at this setting, so I wonder if the assiciation is something still being studied now or is already established? (I have had in situ ductal breast cancer even though not particularly at risk in results here).
I’d say it is established. Recently, a researcher in the American Southwest realized she was seeing a lot of breast cancer in the area (see smithsonianmag.com) and suspected the people were conversos, Jews who outwardly were Christian, but secretly were Jews. DNA proved this. Altho some of the people had no idea, others had menorahs and sacred books hidden away.
No suspicion about it. Probably the majority of the original Hispanic settlers in New Mexico and Southern Colorado are of Jewish descent. But they are Sephardic, not Ashkenazi, so the question was wrong. Researchers only recently discovered that the so-called Ashkenazi breast cancer gene was also common among Sephardic Jews.
And also common in people of their Ashkenazi host populations in the Mediterranean, which Latins of the Southwest also belong to, such as Italians, Greeks, North Africans etc…one not need to create a super mythology to see a simpler answer.
Someone can be ethnically Jewish and a Christian. That’s pretty much what the early Christian Church was for the first 2 decades of its existence.
An example of this is Tay-Sachs Disease, endemic in Southwest Louisiana because some people who are culturally Cajun in that part of the world are ethnically at least part Ashkenazim. The town there called “Kaplan” should have been a dead giveaway.
But geneaology is an imperfect science – before I came down with cancer and became a contraindicated donor of ANY tissue, I assumed when filling out blood marrow donor questionaires and other donor documents based on my south German ancestry that there was a decent chance I had some Ashkenazi DNA in MY cells, and reported accordingly.
First, let me say, I am NOT as educated as some who have posted here on this site. I only know what I have learned from searching through many hard copy and online articles and information I learned from working campus law enforcement for a Medical University where I had a good friendship with the faculty and most students. I started my search after twice being near death due to one of the diseases related to the Ashkenaz ancestry; Ulcerative Colitis. In those two incidents of extreme pain and much blood loss I was advised I had his condition. At that time I had no idea what it was (until the doctor advised me) or what caused it. As I became older I decided to learn more about the problem and cause, because I turned out to be allergic to the primary medications for it. I first started learning that some folks had success in controlling it through diet, which is how I have survived, so far, to age 74, without having the colon removed as recommended by doctors. I decided I would not be able to accept the condition of having a bag on my side. Since going the diet route, which I worked out by myself, I have not had another life threatening event from the condition. Now to what I have learned about the Ashkenazi connection:
Info about the Ashkenazi Jews can be found many places now days with the coming of he internet. The best I have found in various readings shows that; Ashkenaz was a grandson of Noah (see copy and pasted insert part highlighted),
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Genesis Chapter 10 Next >>
Viewing the Standard King James Version (Pure Cambridge). Click to switch to 1611 King James Version of Genesis Chapter 10
1 Now these are the generations of the sons of Noah, Shem, Ham, and Japheth: and unto them were sons born after the flood.
2 The sons of Japheth; Gomer, and Magog, and Madai, and Javan, and Tubal, and Meshech, and Tiras.
3 And the sons of Gomer; Ashkenaz, and Riphath, and Togarmah.
4 And the sons of Javan; Elishah, and Tarshish, Kittim, and Dodanim.
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who led his portion of the Jewish tribe (Ashkenazi’s) into what is now known as Italy and France. Later some of that group moved on into what are now Germany and Russia. Understandably some, or many, eventually married out of their original tribe, which is probably a good thing as that would tend to dilute the genetic problems that occur in too many inbred offspring in the tribal setting. Going on, eventually some of those, from both the inbred and the intermingled came to America, where there would be more intermingling.
Medical research has some time ago determined there are several medical “defects” found in the DNA of many, if not all, the descendants of the tribe of Ashkenaz.
I had not heard about a connection with your medical issue, but then I was not concerned with that, only the issue that affected me.
The internet is a wonderful source for all sort of information. I don’t know how mankind got so far without it.
Here is a link to a page of links to information that might be of value, to you:
http://www.bing.com/search?q=ashkenazi+connection+to+womens+breast+cancer&form=HPNTDF&pc=HPNTDF&src=IE-SearchBox
Also, being retired and not much to do, I would be willing to help you do research (over the internet, not in person), if you would want me to. I make this offer regarding either the Ashkenaz connection or the cancer, either or both.
My last employment was self-employed as a criminal investigator, a talent it turns out I was well suited for. The internet was a huge help in those investigations and I learned to do searches well.
You are free to contact me directly, if you desire, chiron@primary.net is my direct e-mail address. I am Frank Rowlette and live in Kansas City, Missouri, U.S.A., I am NOT trying to do anything except offer help to someone who might need or want it.
A number of years ago I had an event the doctors called “sudden cardiac death” in which the medical record shows I was clinically dead for 45 minutes. As opposed to other’s stories of “near death” I was informed I could remain in Paradise or return to life on earth to try to help others who needed help. I am only trying to comply with the decision I made at that time, in hopes that I can return to God’s presence once again, when that final time comes.
In any event, I wish you a long and productive life, full of joy and happiness as well as good health.
Familial Partial Lipodystrophy – Dunnigan. They tell me its rare, but I have it and many in my family have it. Through the internet I’ve networked with others who have it. When is FPLD-Dunnigan going to get on the 23andme radar? Dr. Garg (in Texas) apparently the world’s authority on FPLD tells us its the result of a mutation on the 1st chromosome.
Re: the statement “Our data shows that many [of these rare] mutations can occur in people outside those ancestral groups,” Unless I’m misunderstanding, it looks like the data is silent as to whether these rare mutations occur in the general population– because the data is incomplete.
Virtually all of us have some genetic inheritance from each of our 16 great-great grandparents, but isn’t information about great-grandparents’ and 2nd great grandparents’ ancestry beyond the scope of information that is collected by 23andme for their autosomal DNA testing? (If I recall correctly, I was asked about where my grandparents were born, but it didn’t go further than that.) Is this self-reported lineage back to grandparents the way that 23andme decides whether someone is Ashkenazi Jewish, French Canadian, or of “the more general population?”
I think that your final conclusion is correct– that screening for these rare mutations should be broader than it is, but the ancestry information that participants submit upon signing up for autosomal DNA testing is too shallow to show that these rare mutations are present in “the more general population.” A rare genetic mutation occurring in someone who is deemed by 23andme to be in the “more general population” might easily have originated with a great-grandparent about whom 23andme collected no ancestry data. (Eg. in my case I have one great-grandmother who was 100% French Canadian–one of the populations that is most studied for these genetic mutations–yet no info. was requested about great-grandparents when signing up for the autosomal DNA test.) As you noted above, many people don’t know much about their ancestry, and that, as much as anything, is a reason for broader screening. People may be part of a group that they don’t know they’re part of.
With the greatly increased global travel of the last century and more importantly the mixing of races and ethnic groups that is occuring world wide is it any wonder????
My thoughts exactly. We must not ignore the fact that more and more humans are intermingling across all sorts of barriers, including race and ancestry.
Not just recently; plenty of mixing occurred in ancient times as well, it just took longer. Irish-looking Turks in Ankara? Sure: Celtic Gauls invaded Italy, Rome bought them off, and later pushed them out; Gauls migrated to Anatolia, formed the kingdom of Galatia, later a Roman province (ref. Paul’s letter to them in the NT), now part of Turkey. And my 11th grade English teacher (blessings upon her) in the early 1960′s said that as an Ashkenazi Jew, she was sure she was part African, saying “my ancestors sojourned 400 years in Egypt, and I know my ancestors were looking at those Egyptian dancing girls.” Meriweather Lewis, according to some people, was killed to suppress evidence of pre-Columbian Welsh migration to America. Spanish sailors with partial Moorish ancestry from the Spanish Armada washed up on the Irish shore when their ships were wrecked, and blended into the Irish population (easier to do because of their common Catholic faith). And genealogists have discovered that Queen Charlotte, the wife of King George III of England, an ancestress of the British royal family today, who came from the royalty of Portugal, had part Moorish ancestry. Naturally that doesn’t get wide mention!
So, people have always had mixed genes. It’s happening faster these days..
People did get around much more than mainstream history records. But there is no evidence the survivors of the Spanish Armada settled in Ireland. The black ancestry of QE II was apparently well known in England at the time of her marriage and coronation and even prior to that.
http://www.pbs.org/wgbh/pages/frontline/shows/secret/famous/royalfamily.html
Go back far enough and we are all related. Case closed.
Well first off being jewish is not being part of a nationality nor is it an ethnic group. Its a religon like any other. Christains could also be considered an ethnic group using the same rationality. So point being this is flawed because you are looking at this in the wrong way. Study the region where people are from and you will find their genetic makeup. This flawed idea of turning a religon into a some sort of nationality is bogus and hurting progress in this area. I know some people might not like my comment, but it must be said because its true.
hiam:
Your claim of authority on the definition of Jewish is spurious at best. Depending upon the nation and the timeframe, Jewish has often been either to describe the religion or the “Hebrew” ethnicity or both. Since modern usage in Western society often refers to Hebrew specifically as simply the Hebrew language, Jewish is very often used to describe people of a particular branch of Semitic heritage as Jewish, to differentiate that ethnic heritage from other Semitic descent, such as the various Arabian bloodlines that are also Semitic in nature. I make no judgment about the precision of such usage, but it cannot be denied that it is highly prevalent.
When used in this regard, Jewish is a term to describe ethnicity exclusively and has no bearing whatsoever on the religion practiced by the individuals that belong to that particular sub-set of ethnicity. For that matter, if used in that context, it becomes ever more important in terms of genetic heritage, as is the subject here.
Your definition of Jewish being applicable only to religious practices is contrary to modern usage in this context, and becoming moreso as time progresses. Also, your emphasis on regional origin is outmoded in today’s globe-travelling society and becoming ever more irrelevant.
If you insist on some sort of semantic precision in genetic bloodline definition, then you marginalize your own contributions by signalling your narrow-mindedness before the debate even begins. You would do well to quit pretending that you don’t know what people mean when they use certain terms and move on to make your points based on that understanding, rather than bogging yourself down in the semantic details of terminology, to the detriment of your own observations.
If you wish to make some actual commentary as to the genetic significance of religious or regional practices, then please do so. Otherwise, your comment may be assumed to be made solely for the purpose of being inflammatory in a forum that has little tolerance for off-subject “trolling”.
Actually Hiam is correct, the study of creation of data sets around a group that has been bottlenecked in various parts of history and for the most part are autosomally related to their host populations is very suspicious. Behar et al showed that Jewish people at not necessarily related to each other and for the most part distinct. The Hebrews coming from Iraq have not been genetically present in any of the Sephardic or EEJ autosomal studies. As of recent EEJ appears to have originated out of Italy, perhaps around 1ad, there are plenty of studies supporting this. Second Sephardic appears to be incredibly 1 to 1 related to Kurds…remove the centric-religious filter and what you see is a much simpler explanation, Sephardic’s might be Kurds brought to Spain by the Moors, after the Re-conquest they simply integrated, or assimilated, or joined a local non Diaspora Roman-Jewish community,
Haim,
Jewish is both an ethnicity and a religion. People are ethnic Jews by way of heredity. Those who practice Judaism are Jewish by choice. Many people have a difficult time understanding that.
I am Jewish, yet I do not practice the Jewish faith. My children’s religion is Christianity, yet they are Jewish.. They are Jewish, because I am. I am Jewish because my parents were Jewish. My father was Jewish (both ethnically and religiously). His mother was Jewish. His dad was not. He practiced Judaism, had a bar miztvah and was buried in a Jewish ceremony. He was ethnically Jewish because his mom was Jewish.
I know it can be difficult to understand, but that does not make it untrue.
Additionally, although Jews have ALLOWED conversion, they have seldom PROSELYTIZED for it (possibly to some extent in the first century, according to some New Testament accusations), but they also discouraged intermarriage without conversion of the Gentile partner. Therefore, if it were possible to get the total data set, it would probably show the majority of conversions involving intermarriage, as opposed to personal choice (e.g. Sammy Davis Jr.), and even single Gentiles who converted were more likely thereafter to marry Jews. So being Jewish IS both genetic and cultural. An earlier poster mentioned the Conversos, whose ancestors were Jews caught in Spain in 1492 when Ferdinand and Isabella overthrew the Moors (then sent Columbus looking for more potential Catholic converts). The ones who convinced the Inquisition they really had become Catholic survived to leave descendants, but many of them kept the “family secret” of their Jewish ancestry, whether or not they secretly practiced Judaism (while outwardly being Catholics) down the generations to today. But even if they did not preserve the family secret, their DNA did.
I am fortunate in that my mother is a brilliant researcher with a particular interest in genealogy and lots of spare time on her hands in recent years. Consequently, I have a very good grasp on most of my genealogical heritage, back to about 6 generations on many family branches. Thanks to the record-keeping of various European noble families, we have of course been able to follow those particular lines farther back than others. However, few modern Americans have the advantage of belonging to groups that kept good lineal records as well as, say, various Hebrew or European families did. I think a good portion of the genetic research being done today has been compartmentalized to various sub-groups simply because of the fact that they are the groups that have kept good records.
In other words, it’s much easier to isolate certain genetic tendencies in sub-groups that are very well defined through assiduous records by their ancestors than it is to identify POSSIBLE variants from those with a less closely defined heritage.
Therefore, it is understandable that researchers must start with smaller subgroups and what they know before extrapolating their results to larger, less well-defined groups, especially “the poopulation at large”, as it were.
What we are seeing here is the scientific process of building a database, a massive undertaking that we are still in the early stages of developing. To look at a snapshot of the progress made so far and make judgments based upon it would be a mistake.
I think that as time wears on and more data is gathered, we will begin to see so-called “rare” mutations are far more commonplace than originally thought, and that the implications of certain genetic characteristics ascribed to genetic sub-groups will not only help us understand the human genome better, but will also have historical implications to help us understand group migrations, etc.
For example, what if it were found that two different isolated sub-groups shared a certain “rare mutation”, but were vastly separated geographically? Speculate that a genetic marker formerly ascribed exclusively to native Alaskan Inuit tribes were also found to be highly prevalent in Australian aborigines, but nowhere else in the general human population? What sort of effect would that have on current migration theories?
While such revelations are relegated to mere speculation at present, I anticipate the advancement of these studies will be “the new frontier” in scientific progress as we reach “critical mass” in the data-gathering process. Right now, we can only wait and watch, and try not to judge prematurely.
And what type of mutations might these be?
A rudimentary knowledge of genetics says that most devestating diseases are recessive genes in the population. It’s takes two of these genes to have the disease in most cases. Therefore when there is only one of these genes and marriage is in diverse groupings the disease is rare. Where for reasons of isolation or religion, people intermarry to a greater degree than the general population,these genes will be expressed because both the man have the gene that was hidden in their genome. I think these genes were always present as you are seeing now, but not expressed as the disease. Nothing new!
And of course, we all know that everyone who knows their ancestry also did genetic tests on each of those ancestors to ensure that the father-of-record is the actual father. ;-)
Somewhere between 10 and 20 percent of births in the modern US have a genetic father different than the father-of-record. (Several studies have confirmed this, as far back as the 1950s.) I see no reason to believe that the percentage in the past was zero, or even close to it. That means that there is/was far more mixing than it is polite in current society to admit, and that even those who think they know their ancestry probably don’t know it as well as they think.
Screening should be broader for all of these factors. One reason some hereditary disorders are not tested for, particularly in preconception or early pregnancy, are due to stereotypes that have stuck around even though humans are much more mobile and intermingling and combining different ethnicities and different genetic mutations. My son and I have G6PD deficiency. I am the first person, in our family to be diagnosed and I was diagnosed at 34, after nearly dying for side effects of contraindicated medications and medical trauma. Most doctors still think that it’s extremely rare (it’s not that rare, but it is under-identified) and that it occurs in darker skinned males of African or Mediterranean origin and it is widely believed that because it is x-linked that women rarely have it because it would require and x from each parent. G6PD Deficiency does not always behave as typical x-linked recessive, and women who are considered “carriers” are more accurately described as “partially deficient”, and many may never have a symptom, during times of medical trauma, or during childbirth, they may have symptoms that are hard to resolve without the information about G6PD deficiency status. The most common, and least expensive, test for G6PD Deficiency does not detect these partially deficient individuals, so many women who are tested (often after a son or other family member is diagnosed) think they are not G6PD Deficient and they assume they are not a carrier or partially deficient based on incomplete information. One reason mine went undetected, and untested even in pre-conception and early gestational screening is because I’m female and pale and I burn within 10 minutes of being outside. Even though my ancestral origins were not known (I’m adopted and had zero family medical history or information on ethnicity), doctors and specialists and even laypeople made assumptions. Assumptions kill. I’m fortunate to have survived, and hopefully we have adjusted my son’s exposure to contraindicated substances so he doesn’t go through the hell that I have been through in my life because we didn’t have one little piece of information… For more information, please check out the very informative G6PDdeficiency.org site (for the record my mutations did not show up in my 23andme.com testing, though most common ones are tested for).
I’m curious why the report did not distinguish between harmful and beneficial mutations.
Both my kids had sickle cell trait, and we are white caucasions. There MIGHT be some mellungeon in my past family DNA, but don’t know. Not a lot of accurate family records prior to the civil war in rural backwoods areas. Imagine the surprise when we got the report from the health department after my son was born. Had no idea….but now it makes sense that my family has problems with blood clots, strokes, blood pressure and diabetes.
This article really says nothing.
Mutations never produce anything better _ always something worse as every comment here reinforces. So tell me, how did we mutate from something out of the sea and climb up on land and then come out of the trees and then go to the moon?
Exactly right. However, this is not simple mutation, but DNA transfer amongst individuals and species. IOW, I expect that we will animals like Dogs, and cats get smarter then they were 10K years ago.
Some mutations are incredibly useful, some cause disease. Your blanket statement just shows your lack of understanding of genetics AND the reality of evolution.
The ccr5-Δ32 mutation confers HIV-1 resistance to those with a double copy of the allele (homozygous). The mutation also confers resistance to plague and smallpox while increasing susceptibility to west nile virus.
The mutation for sickle cell trait seems to provide resistance to malaria for a population that came up in an environment rife with it (Africa).
I could go on, instead I suggest you read a few books about genetics, mutation, and evolution.
The fact that mutations like these are showing up, would indicate that these are viral in nature. IOW, they have the ability to spread.
Once the facts are in, which will take years of tedious research without biases, everyone will be shocked to know that mutations are a common occurrence regardless of region or ethnicity. If what formed life exist everywhere, then what causes mutations exist everywhere, perhaps to varying degrees but it exist. We speak of ethnicity, sub-groups, and regions, but what happens when we just don’t fit into one of these categories. Then and only then are we a true mutation and not victims of our DNA. Does it matter that I do not share the medical history of my family? My medical problems are unique to me as I myself, so is it I am adopted? How could this matter as I am still from the same sub-group? Aren’t all of our mutations the same in this sub-group and this region? This research gives rise to more questions to be answered then it answers more questions.
We’ve seen this in action in my family- my daughter’s newborn screening showed the Hemeglobin E trait- normally found in Asian & Mediteranian populations. But upon further digging, we found it had been passed on through my great grandmother, who’s family is almost 100% Polish. Interestingly enough, her family had come from a region of Poland where the beta Thalasemia trait is common, and no one in the family inherited that. Which is good, because the two traits together are almost invariably lethal.
people are all mixed up!
Useless story with no meat. People came to this story wanting to see numbers and the mutations theyre for. Pointless story intended to draw readers who get to read. . .nothing.
“This second possibility has far-reaching implications. Couples planning to have children are often screened for genetic mutations that could cause inherited diseases in their children. Typically, they are screened for specific mutations thought to be most common in their ancestral group. Our data shows that many mutations can occur in people outside those ancestral groups. Add to that the fact that many people might not know all the details of their ancestry and ***the argument for broader screening becomes stronger.***
Ka-Ching
Can anyone clarify the pemphigous vulgaris skin disease?
WE ARE BECOMING ALIEN MUTANTS-EVERY DAY I WAKE UP EXPECTING THREE HORNS PROJECTING FROM MY FOReHEAD, LIKE A DINOSAUR!!!!
There are a lot more mixed race people out there too. Census says its the fastest growing catagory. Its seem logical that mutattions could carry over