Ancestry and Disease in the Age of Genomic Medicine

Review Article
Ancestry and Disease in the Age of Genomic Medicine
http://www.nejm.org/doi/full/10.1056/NEJMra0911564?query=TOC#t=articleTop

W. Gregory Feero, M.D., Ph.D., Editor, Alan E. Guttmacher, M.D., Editor

Ancestry and Disease in the Age of Genomic Medicine

Charles N. Rotimi, Ph.D., and Lynn B. Jorde, Ph.D.

N Engl J Med 2010; 363:1551-1558 October 14, 2010

Human genetic data are accumulating at an ever-increasing pace, and whole genome sequences of individuals from multiple populations are now publicly available.1-3 The growing inventory of human genetic variation is facilitating an understanding of why susceptibility to common diseases varies among individuals and populations. In addition, we are gaining insights that may improve the efficacy and safety of therapeutic drugs. Such knowledge is relevant to fundamental questions about our origins, differences, and similarities. Here, we provide a brief review of the current knowledge of human genetic variation and how it contributes to our understanding of human evolutionary history, group identity, and health disparities.

Bridging the Divide between Genomic Science and Indigenous Peoples

Bridging the Divide between Genomic Science and Indigenous Peoples
http://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00521.x/abstract

The Journal of Law, Medicine & Ethics, Volume 38, Issue 3, pages 684–696, Fall 2010.

Bette Jacobs, Jason Roffenbender, Jeff Collmann, Kate Cherry, LeManuel Lee Bitsói, Kim Bassett, and Charles H. Evans, Jr.

The new science of genomics endeavors to chart the genomes of individuals around the world, with the dual goals of understanding the role genetic factors play in human health and solving problems of disease and disability. From the perspective of indigenous peoples and developing countries, the promises and perils of genomic science appear against a backdrop of global health disparity and political vulnerability. These conditions pose a dilemma for many communities when attempting to decide about participating in genomic research or any other biomedical research. Genomic research offers the possibility of improved technologies for managing the acute and chronic diseases that plague their members. Yet, the history of particularly biomedical research among people in indigenous and developing nations offers salient examples of unethical practice, misuse of data, and failed promises. This dilemma creates risks for communities who decide either to participate or not to participate in genomic science research. Some argue that the history of poor scientific practice justifies refusal to join genomic research projects. Others argue that disease poses such great threats to the well-being of people in indigenous communities and developing nations that not participating in genomic research risks irrevocable harm. Thus, some communities particularly among indigenous peoples have declined to participate as subjects in genomic research. At the same time, some communities have begun developing new guidelines, procedures, and practices for engaging with the scientific community that offer opportunities to bridge the gap between genomic science and indigenous and/or developing communities. Four new approaches warrant special attention and further support: consulting with local communities; negotiating the complexities of consent; training members of local communities in science and health care; and training scientists to work with indigenous communities. Implicit is a new definition of “rigorous scientific research,” one that includes both community development and scientific progress as legitimate objectives of genomic research. Innovative translational research is needed to develop practical, mutually acceptable methods for crossing the divide between genomic researchers and indigenous communities. This may mean the difference between success and failure in genomic science, and in improving health for all peoples.

Three recent articles using DNA for genealogy

The following articles use DNA testing in determining the genealogical connections in the families studied:

• Daniela Moneta "Virginia Pughs and North Carolina Wests: A Genetic Link from Slavery in Kentucky," National Genealogical Society Quarterly vol.97, pp.179-194 (September 2009).
• Alvy Ray Smith, "The Probable Genetic Signature of Thomas¹ Riggs: Immigrant to Gloucester, Massachusetts by 1658," The New England Historical and Genealogical Register, vol.164, pp.85-89(April 2010).
• Alvy Ray Smith, "The Probable Genetic Signature of Edward¹ Riggs: Immigrant to Roxbury, Massachusetts, in 1633," The New England Historical and Genealogical Register, vol.164, pp.95-103(April 2010).

In his two articles, Dr Smith introduces his own method of showing genetic ancestry which does not follow any of the usual methods. While some like his method, I find it less informative that the standard marker site, marker value pairs used by the genetic genealogy community.

Genetic Privacy

The following article is interesting from several angles; the use of the SMGF results in combination with the Family Search database; and the question of maintaining privacy of genetic results. The different orientations of medical researchers with Institutional Review Boards to consider, and of genealogists searching for identifiable links makes for an interesting tension in the research protocols each brings to the reading of this article.

Since I am a multiple relative of Emma Hale, wife of Joseph Smith, I have an interest in the early Mormon families.

http://scpgen.blogspot.com/2009/10/ancestors-of-emma-hale-wife-of-joseph.html

http://scpgen.blogspot.com/2010/06/mormon-or-church-of-jesus-christ-of.html

Comments?

Steven C. Perkins

========================

Copyright © 2009 The American Society of Human Genetics. All rights reserved. The American Journal of Human Genetics, Volume 84, Issue 2, 251-258, 13 February 2009
doi:10.1016/j.ajhg.2009.01.018

Inferential Genotyping of Y Chromosomes in Latter-Day Saints Founders and Comparison to Utah Samples in the HapMap Project

http://www.cell.com/AJHG/retrieve/pii/S0002929709000251 [Link to PDF here]

Jane Gitschier1,*
One concern in human genetics research is maintaining the privacy of study participants. The growth in genealogical registries may contribute to loss of privacy, given that genotypic information is accessible online to facilitate discovery of genetic relationships. Through iterative use of two such web archives, FamilySearch and Sorenson Molecular Genealogy Foundation, I was able to discern the likely haplotypes for the Y chromosomes of two men, Joseph Smith and Brigham Young, who were instrumental in the founding of the Latter-Day Saints Church. I then determined whether any of the Utahns who contributed to the HapMap project (the ‘‘CEU’’ set) is related to either man, on the basis of haplotype analysis of the Y chromosome. Although none of the CEU contributors appear to be a male-line relative, I discovered that predictions could be made for the surnames of the CEU participants by a similar process. For 20 of the 30 unrelated CEU samples, at least one exact match was revealed, and for 17 of these, a potential ancestor from Utah or a neighboring state could be identified. For the remaining ten samples, a match was nearly perfect, typically deviating by only one marker repeat unit. The same query performed in two other large databases revealed fewer individual matches and helped to clarify which surname predictions are more likely to be correct. Because large data sets of genotypes from both consenting research subjects and individuals pursuing genetic genealogy will be accessible online, this type of triangulation between databases may compromise the privacy of research subjects.

23andMe Ancestry Finder versus 23andMe Relative Finder

When I logged into 23andMe last night and went to Relative Finder I had 506 matches. I sent sharing invitations to 5 of the new matches and I sent a separate invitation to a Public Profile match. The remaining match was from someone with multiple people on his profile.

People who appear in Relative Finder share at least 7.5cM of genetic data with you in one location. Once you agree to compare your genome in Ancestry Labs, Family Inheritance: Advanced you may find that you share segments between 5 and 7.5 cM. The matching in Relative Finder occurs automatically for everyone in the 23andMe database. Of course, each person can opt out of Relative Finder.

Ancestry Finder uses the lower 5 cM cutoff and can match you with people who would not automatically appear on Relative Finder IF the person has filled out the optional "Where are you from" survey. The survey asks for location information on you, your parents and your grandparents. This data is used to show where the grandparents of people who match you in Ancestry Finder were born. There are a number of limitations to this data: current country names are used which may not really reflect the ancestry/ethnicity of the match; the data is only as good as the information the person completing the survey knows; just because a match has grandparents from X country it does not mean you do.

Both Relative Finder and Ancestry Finder should be used to research your ancestry. At this time Ancestry Finder is more difficult to use and it is hoped it will be come more like Relative Finder or be merged with it to make it easier to use.

The provision for Public Profiles in both systems has made it easier to determine if some matches might be more useful that others. It also provides the opportunity for committed genetic genealogists to let others know they are willing to share data.

FDA and Senator Hatch hold hearings on DTC DNA testing

The big news last week were the hearing held on Direct to Consumer (DTC) DNA tests by the FDA and by Senator Hatch. Katherine Hope Borges of the ISOGG made a statement at the FDA hearing which is reproduced at the Huffington Post by Megan Smolenyak. Katherine was the only speaker to address genetic genealogy issues. The rest of the speakers discussed various medical aspects of DNA testing.

Links to follow.

Results at 23andMe and at FTDNA

Today I have the following results:
23andMe:

• 497 matches
• 122 sharing genomes
• 18 Public profiles
• 338 contacts sent
• 128 accepted 22 declines

Closest relationship identified, 3rd cousin once removed, 4 matching segments
Closest waiting for reply, 2nd cousin with 12 matching segments
1 of 9 1st cousins is also on 23andMe, 41 matching segments (share 6 of 8 Great grandparents)

FTDNA:

• 64 matches
• 30 emails sent

Closest relationship identified, 4th cousin once removed.

Upgrade sale at FTDNA: 8 July - 19 July 2010

Dear Family Tree DNA Customer

Over the last several years, due to the unmatched growth of our database, numerous people have confirmed and found new connections with others of their surname, and adoptees and descendents of adoptees have even found their biological surname.

These successes are due in large part to the size and quality of our database, which, with your help, has achieved critical mass. We have made tremendous progress, but we feel that we can do more. If you have tested 12, 25, or 37 markers, an upgrade to 37 or 67 markers could provide the relevant connection that you or your matches have been waiting for.

Family Tree DNA is dedicated to supporting this effort. From July 8th through July 19th, we will reduce all our Y-DNA upgrade prices.

Current Group  SALE Price

Y12-25  $49    $35

Y12-37  $99    $69

Y12-67  $189  $149

Y25-37  $49    $35

Y25-67  $148  $109

Y37-67  $99    $79

To order this special offer, log in to your personal page and click on the special offers link in the left hand navigation bar. A link to the login page is provided below. ALL ORDERS MUST BE PLACED AND PAID FOR BY MIDNIGHT JULY 19th TO RECEIVE THE SALE PRICE.

http://www.familytreedna.com/login.aspx

A notice of this sale has been sent to those customers who qualify for these Y-DNA upgrades.

We would also like to take this opportunity to inform you that registration has begun for The 6th Annual Conference on Genetic Genealogy for Group Administrators, which will be taking place on October 30-31, 2010. You can find more about it here

As always, we appreciate your continued support.

Bennett Greenspan
President
Family Tree DNA
www.familytreedna.com
"History Unearthed Daily"

© All Contents Copyright 2001-2010 Genealogy by Genetics, Ltd.

My statistics at 23andMe and at FTDNA

I have tested my autosomal chromosomes at both 23andMe and FTDNA.

At 23andMe in Relative Finder I have 464 people with matching chromosome segments. My largest match is with my 1st cousin at 19.79% of our DNA. Most 1st cousins will be around 12.5% but we share 6 of 8 Great Grandparents so we have more matching DNA than most 1st cousins. The lowest amount of DNA I have with someone is .08% and that was the first person I was able to find a match with as 10th cousins once removed. 106 people are currently sharing genomes with me which allows us to see on which chromosome we have a match.

The majority of my matches are on one or another of chromosomes 1 through 22. However I have 9 people who have 10 shared segments with me on the X chromosome which, as a male, I inherited from my mother. By mapping the start and end locations of the shared segments I can see who may share a common X ancestry with me or with each other. In this case my 1st cousin shares 2 segments with me and 1 of those segments with me and two brothers. I partially share a segment with a mother and daughter and 3 other persons. And one of those persons shares half a segment with another person.

When males share an X segment it means they are related through their mothers' ancestry. When a male shares an X segment with a female they can be related on his mother's ancestry and on either her mother's or father's X ancestry.

Unless one or both of your parents also takes the 23andme test, it can be difficult to "phase" your results, in other words, to be able to assign a segment to your mother's or father's ancestry. Until this can be done, you can't know if two people who match you at the same location match your segment strand from either your mother or your father. This means that you can't say that it means they have the same ancestry to each other as they have to you. If your parent's are deceased, you may be able to phase your results by testing siblings of you or your parents.

I have definitely identified 6 relationships at 23andMe. Over 50,000 people have tested at 23andme in the past two years.

At FTDNA in Family Finder I have 53 matches. Because FTDNA didn't start Family Finder until recently, the number of matches is much smaller than at 23andMe. However, since Family Finder only tests for ancestry, it is believed that the people testing will be more knowledgeable about genealogy than those at 23andMe. So far I have also identified 6 connections at FTDNA, the same as at 23andMe but twice as many per number of sharing matches. At this time FTDNA does not show matches on the X chromosome but it has said it will do so in the future.

I have also had autosomal testing done with Sorenson Molecular Genealogy Foundation but they have not yet released their results. They have tested over 100,000 people and have pedigrees attached to most of those.

Ancestry Finder Beta at 23andMe

There is a new beta program at 23andMe called Ancestry Finder. This program uses the information from the survey on "Where are you From?" to map segments of your autosomal chromosomes to various nationalities. No time line has been given for rolling this out beyond the beta testers.

Some questions have been raised on whether this will be of practical use for Native American or African American testers since the number of persons from each group participating in 23andme is low. There is also some concern from European Americans who have long lines of ancestors born in America that the program will not give them much of interest.

It is hoped that those who have already completed the survey will be allowed to edit their replies to add information on ethnicity to supplement the location information.

A review has been posted at the Your Genetic Genealogist blog.