December 01, 2010

Breast-cancer causing mutation in Ashkenazi Jews came from Europeans

The interesting question is: why did this become frequent in AJ? If this mutation did indeed enter the AJ gene pool half a millennium ago, then it may be within the reach of genealogists and historians to uncover its origins.

European Journal of Human Genetics , (1 December 2010) | doi:10.1038/ejhg.2010.203

On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations

The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400–500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.



Gioiello said...

I am feeling that I am completely winning.

Jack said...

"I am feeling that I am completely winning."
In the sense that Italians originated in northern Russia?
An "out of Russia" hypothesis for mankind?

pconroy said...

My thinking on this is like certain sphingoid diseases, which are common in Aj's and known to both:
1. Increase the density of neuronal connections
2. Raise IQ in carriers

That in this case, the breast cancer variant raises the rate at which connective tissue is generated, which may also be expressed in neuron growth, and therefore follow a similar trajectory to the sphingoid diseases.

I also theorized a few years ago, that because of the huge selection pressure on AJ's for high IQ, that they would have sucked up any advantageous allele floating around in Europe - by which I mean that a few such advantageous alleles coming into the AJ genepool, would get selected for and spread. This seems to confirm this.

Gioiello said...

In the sense that Ashkenazim (but also all the other Jewish communities) are linked with the countries where they live (or lived) and a little of Ancient Jews. That they had many of East Europeans was demonstrated also by the high percentage of CCR5d32 among Jews from Lithuania (40%), as I said to Sam Vass some years ago. This is the truth, you like it or not.

n/a said...


Here's an introduction to natural selection for you.

Jack said...

I have an idea similar to pconroy's although not identical.
A selective process.

Jan said...


you are the best example, how one with agenda misuse scientific data and conclusions to produce "right" results.
You've got enough remarks from Dienekes on this issue.

In case you still don't understand the point, what about this statement:
"Since about a half of Lithuanian Jews are CCR5d32 carriers, it's clear that this community is a source of CCR5d32 mutation."

horacioh said...

See:"The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic determinant of Parkinson disease (PD) in Ashkenazi Jews and North African Arabs with PD." ...with carrier frequency of 29.7% among familial and 6% in sporadic Ashkenazi Jewish PD cases. Thaler A. et al 2009.
Other "From;Am. J. Hum.
Genet. 2000, Richards M,et al: “We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the LGM, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the current mtDNA
From;-2001- Nicole Maca-Meyer, BMC Genetics 2001
“The second cluster groups minor haplogroups
W, I and N1b -in Neolithic period- ...only I and N1b have been also detected in Egypt and Arabia.”

Other: From Behar et al 2006
"High incidence of Hg N1b in Ashkenazi Jews. Hg N1b
is virtually absent in Europeans (0,20% or minor) but appears at frequencies
Of 3% or higher in those from Levant, Arabia, and
Egypt (Richards et al. 2003; Kivisild et al. 2004; unpublished
results of Tartu and Haifa groups).
…In total, we have identified four Ashkenazi founding
lineages, three within Hg K and one in Hg N1b, deriving
from only four ancestral women and accounting for fully
40% of the mtDNAs of the current Ashkenazi population
(8,000,000 people). The second
most common lineage is within Hg N1b and corresponds
to an additional or more 800,000 people.We compared
the pattern of lineage distribution seen in Ashkenazi Jews
with a global database of 30,000 mtDNAs, 13,359 of
which are from populations in which Hg K and N1b
are present and we could not detect anything
similar… For example in European Caucasian
Populations were determined. The frequency of 18 haplotypes was found to account for only
20.8% as whole of the European Caucasian mtDNAs—a very significant
difference compared with the Ashkenazi Jews,
for which four complete sequence haplotypes comprise
42% of the mtDNAs…"

Other: from mine article April 2001 and Oct. 2010 This 42% mtDNA -include "N1b" “G nucleotide variant of M.E. and E.A.” - individuals carrying these mitochondrial markers- as well from a fifth to seven mothers that includes the "L1, l2" and "M1" haplogroup also with origin from the Wide or extending Middle East that includes Abyssinian region – who represents 50 % mtDNA of the nowadays Ashkenazi community.
See too: Laurie J. Ozelius et al 2006.
It has been seen, that Neolithic Nb1 were at High frequencies in LKB culture also is present striking in Ashkenazim today at high rates (10 at 12%) perhaps for natural selection or other events.
If the Ashkenazim with only 1200 years ancient, likely born in massive
Coming from Alexandria Egypt –first in number- and the Levant –second
in number and before in times towards II century AE -or before yet- to Central Italy in VII century AE – when Muslim invaders- and after the North and the East of Europe, they possess actually –more in ancient times- maternal mitochondrial markers mtDNA L1,L2 (4%) from Abyssinia, and the sibling N1b (10-12%) and M1(2%)-Behar el al 2006, Also Ovadia et al 2010- linked with L3 from Abyssinia – Ethiopia and Eritrea also Somalia- and Near East.
Remember that buried and graves in Jewish graveyards and catacombs of Tuscan, and
Alsace as too Rhineland cities take a lot of Egyptian ornaments and
display figures from these, as well as Y and mtDNA markers - .
It likely proves the existence of Abyssinian people in ancient Israel or, also it proves the fact that the former Israelite people had Abyssinian
numerous masculine markers -E3b, 4S etc., including partially like NE markers- as well enough known, as
and feminine markers like L1L2.N1b.M1, showing a feedback between
people into Ethiopia and Israel in ancient times.

Jack said...

Gioiello is not going to like you.

Gioiello said...

I think Horacioh is totally wrong and I can demonstrate it, but if Dienekes doesn't let pass my postings I am not able to demonstrate it. I am waiting for the next researches confidently.

Sonya Rose said...

Thanks for explaining this in more details... First time, I heard of BRCA was last week. I am waiting now to see the results of my BRCA mutation test, on eggshells: I have been diagnosed with Invasive Lobular Carcinoma (ILC), age 39. This test will make a difference in which path I will take for surgery: How to treat the cancer most effectively. said that my mtDNA is X2b, the oddball one, ancient link of a mysterious origin (My mother and her side of the family come from Germany/Switzerland and I'm sure goes farther back than that...). I will have to have a mastectomy if I have the gene mutation, of course. Now, I'm reading on the internet about the recent news on breast implants. I've never had them, but, some women who have for breast reconstruction after cancer surgery now are learning about the rare cancer risk -- Lymphoma. On, my mtDNA shows that I carry an elevated risk for that than average. Oh, gosh, all this science can save our lives and help with our decisions; also, our dreams play a big part. I was led to seek help from a women in my last divine dream. She said to go get checked. So, when I woke up, I did do just that... now, after being diagnosed... I discovered my type of breast cancer/grade 3 is well known to go under the radar... and able to spread to other parts of the body, a fast growing kind. I just hope that we got this time. I think... I hope so. And, that lady who came to me in my dream must have been Godsent. I battled Chronic Lyme Disease...I can battle this. Godspeed~