Investigation of Ancestry Testing by DNA Sequence Analysis

Debora Mukaz

BACKGROUND

• Series of documentary by Henry Louis Gates, African American Lives and II, which tried to identify the ancestral and racial background of African American celebrities: http://www.youtube.com/watch?v=o1Oe4DnJwKM

• The first-entry of the series hit close to home when they tested the famous neurosurgeon, Ben Carson, and found out his ancestors were from my ethnicity (Lunda).

• Discussion with Professor Kaehler, who then told me that racial and ancestral concepts in genetics were not as simple as the document was trying to portray them

• Desire to learn more about the DNA testing companies

HISTORICAL DEVELOPMENT OF THE CONCEPT OF ANCESTRY AND RACE

• Herodotus(fifth century, B.C): father of Greek history, he studied different populations mostly around the Mediterranean

• Carl von Linnaeus(1707-1778): Swedish scientist who classified humans into separate categories using the binomial system

• Anders Retzius(1796-1860): another Swedish scientist who introduced a system of classification of human ‘races’ using the cranio-metric criteria

• Charles Darwin( 1809-1882): argued against full infertility in humans and concluded that there was one human species

• The major advance in the study of human ancestry has been the introduction of genetic markers after World War II

Information in DNA

Information in DNA

• DNA transmits the information in its sequence of four types of bases, which are adenine (A), thymine (T), guanine (G) and cytosine (C).

• To study ancestry two types of DNA are used: Mitochondrial DNA and Y-Chromosome DNA

• Y-chromosome DNA is transmitted from father to son

• mitochondrial DNA or mtDNA is exclusively inherited from the mother.

• For the purpose of this study, only mtDNA was used since we wanted to have both male and female subjects .

Mitochondrial DNA or mtDNA

• mtDNA is found in the mitochondrion, which is a cytoplasmicorganelle with its own membrane

• mtDNA genes are exclusively transmitted by the mother• The only region of the mtDNA that has significant variability is the

D-loop, or control region, whichis highly variable and rapidly evolving relative to the rest of the mitochondrial genome.

• The control region is divided into 2 distinct regions known as hypervariable 1 ( HV1 or HVR1) and hypervariable 2 (HV2 or HVR2) .

• mtDNA relative small size and the fact that it has unrepaired and faster mutations make it a good target to identify differences among individuals and populations

mtDNA analysis to study ancestry

• By coupling mtDNA sequence analysis and RFLS analysis, a fairly refined human phylogenetic tree has been produced, with branches for different geographic regions of the world.

• the ability of restriction analysis to trace human genetic history based on the observation of Restriction Fragment Length Polymorphisms (RFLPs)

• mtDNA sequencing: Frederick Sanger’s method and mirofluidics environment

Experiment

• 5 consenting subjects were selected based on their historical sense and their geographic ancestry

• The subjects’ mtDNA samples ( obtained from cheek swabs) were sent to 4 different companies: The Genographic Project, DNA Family builder, DNA Heritage and Family Tree DNA

• the tests, the mtDNA regions used by the companies and the results obtained.

• Advantages and disadvantages of using mtDNAtesting to find out about ancestry were assessed

Comparisons of tests and used mtDNAregions

• Each company tested specific sites of the mtDNA control region.

• Tested regions were either identical among companies or overlapped

• Family Tree DNA is the only one to have tested a backbone of 20 SNPS

Comparison of results: haplogroups

• To keep the names of the subjects anonymous: AA, BB,CC, DD and EE were used in place of their real names

• For all the 4 companies, AA belonged to Haplogroup L subclade L1

• For all the 4 companies CC belonged to haplogroup H

• As for DD, all of the companies show him belonging to haplogroup A

• For 3 of the 4 companies (Family Tree DNA, DNA Heritage and The GenographicProject), BB belonged to Haplogroup T while DNA family builder identified BB with haplogroup H.

• As for EE, 3 out of 4 companies (The Genographic Project, DNA Heritage, Family Tree DNA) identified the subject as belonging to haplogroup H while the fourth one, DNA family builder identified EE with haplogroup T.

• Some of the companies such as DNA Heritage, were very specific since they gave the subclade and subgroup of subjects’ haplogroups

Comparison of results: migration patterns of haplogroups

• Haplogroups T and A covered such broad swaths. Both haplogroups T and A included the most part of Europe and Asia

• As for haplogroups L and A, they are more mostly well defined within the borders of certain continents. L is an African haplogroupwhile A is mostly found in East Asia and is present with some populations in the Americas.

Debora Mukaz’s results

• The format and content of information a subject received from each of the 4 companies was quite variable. Some limited descriptions of human migration were present but often times they were very vague.

• For all the 4 companies, I belonged to Haplogroup L subclade L1. L1 is mostly found in Central Africa

Advantages of using mtDNA testing to find out about ancestry

• Help people get a better understanding of their different haplogroups

• Reconnect individuals with their ancestral history

Disadvantages using mtDNA testing to find out about ancestry

• All the results were given as haplogroups and migratory maps, which often times, did not give specific and clear information about the subjects’ backgrounds

• Can mislead people especially those who have no basic knowledge of genomics

• Companies were not specific so people might be disappointing for people who expected more

• Some of the companies go as far as to say they can predict race. Yet, race is a social construction