Powerpoint Presentation of this Lecture

Moderator
john a. powell, JD, Executive Director, Institute on Race and Poverty, Minneapolis, Minnesota

Presenter
Ricky Kittles, PhD, Co-Director Molecular Genetics, National Human Genome Center, Howard University, Washington, DC

john powell:
Dr. Ricky Kittles has been very much in the forefront of raising the issue of the use of DNA to trace African ancestry. There's some question on whether or not we can do this right now. If we cannot do it right now, we probably will be able to do it in a very short period of time. Having said that, Dr. Duster's question remains: What are the social and political implications of this technology?

One additional comment on Dr. G. Coraves comments about whites being black. This is a very complicated question. One way of thinking about it is that whiteness never was about blood, so to say whites have black blood in them, doesn't mean they cease to be white, any more than saying that blacks having white blood in them means they cease to be black. As Dr. Duster suggests, if race is socially constructed and we say that a lot now, it means there's no definitive biological indicator that tells us what race we are. Of course, people around the world construct race differently. The point is, as Dr. Duster suggests, that the political and social agenda of how race is constructed and used is the real cutting edge issue. It's not simply the scientific matter of measuring blood or genes. With that, I'll give you Dr. Kittles.

Ricky Kittles:
In many West African cultures or traditions, when a young person comes into an area with a lot of elders in the community, that person asks the elders for permission to speak, so now I am asking the elders for permission to speak. Thank you. I share Dr. Duster's ambivalence with regard to the genetics and genealogy of African-Americans but for slightly different reasons. The challenge is to articulate the promise and the limitations of this work. This is not an exercise in genetics but is a social project, a project that's important to me as an African-American and to the African-American community.

Interest in research in genealogy has increased enormously over the past decade. We see this in the many organizations that sponsor this research and in the genealogical societies. For many this is a hobby; for others it is a life-long passion. With the advent of genetics and the genetic data from the Human Genome Project, there's been increased attention to using genetics to infer ancestry or to unravel the mystery of genealogy. This is an exciting, complex, sensitive, and controversial issue. It is probably the most controversial as it relates to African-Americans. So I am going to share with you its promise and also its limitations.

African-Americans have a particular interest in understanding genealogy. Eighty percent of African-Americans respondents to a recent web-based poll on africana.com believe that it would be important to use DNA to determine their ancestry through DNA testing. The African-Americans who go to that Web site are especially interested in wanting to learn about African identity or some personal cultural identity so this may be a bit skewed but still it is a high number. African-Americans are particularly interested because of the unique history of the population. The African-American population is what some call a "macro ethnic" group. As such, it has its origins in the US from indigenous African populations that were enslaved in great numbers during the Trans-Atlantic slave trade that took mainly took place from about 1600 to about 1850. When many African-Americans think about their ancestry, they think about the continent of Africa. You say, "Well, I know I am African-American, I have some African ancestry, but I don't know from where." This uncertainty bothers some of us more than others. I appreciate Dr. Duster's comment about his grandmother being Ida B. Wells. Many of us don't have grandmothers or grandfathers that had that much of an impact in terms of centering one's identity in that lineage.

The enormous African continent is rich in diversity - cultural diversity, linguistic diversity and biological diversity. Five major language groups are spoken on the continent: Khoisan, Niger-Congo, Nilo-Saharan, and Afroasiatic. Over 2,000 dialects are spoken from these language groups on the continent. It is very rich in cultural diversity. It's also rich in genetic and biological diversity. We see the full gamut of the phenotypes that we see around the world in the continent of Africa and we see the same thing as it relates to a wide array of genetic diversity. Africa was the place of origin for modern humans and one would expect to see this range of diversity that is exemplified throughout the rest of the world. When I talk about the genetics and the genealogy of African-Americans, it is not population genetics or human genetics; it has to be placed into some context. I hope to place it into a historical, sociopolitical and a psychological context.

Many of us think about the horror of the middle passage experience. We look at the genetics of complex diseases and the health of African-Americans and cannot fail to take into account the biological and genetic consequences of this experience. Hundreds of lineages, millions of individuals and families, were brought here and mixed up. Some made it and some did not over the months of time it took to get here. That's what they call a bottleneck, where you have a large group of selected individuals who give rise to another population. An enormous genetic bottleneck occurred and we are trying to uncover and unravel some of that information.

So what are some of the genetic features of the African-American population? We know that there is high genetic diversity, mainly due to diverse African ancestry. We also know that an appreciable amount of that diversity is due to the mixture with non-Africans, mainly Europeans, and to a small extent Native Americans, during and after the period of slavery here in the US. We know that the pattern of variation differs across the US.

Let's talk about this African ancestry. We know from historical shipping and naval records that enslaved Africans came from this area of west and central Africa, from Senegal to Southern Angola, and also eastern Africa, the island of Madagascar and Mozambique. We have pretty good documentation of the ships and the companies and the countries that were involved. In some cases, we know the numbers and the actual ethnicity of those who were enslaved.

The region of West and Central Africa encompasses a broad range of variation that exists throughout the continent. For a while during slavery, the plantation owners had preferences for particular African groups. For instance, Charleston, New York, New Orleans, and Richmond Virginia were large ports of entry. In South Carolina, the plantation economy was based on rice and indigo for a long time. Many of those plantation owners wanted Africans who were familiar with the practice of growing rice, so they would request Africans from Upper Guinea, which is Senegal, Senegambia, Sierra Leone, Liberia. In Virginia, many of the plantation owners were involved in tobacco farming, and for some reason, they requested Gold Coast Africans, Guineans, individuals from that region of what they call the Gold Coast of Africa. People there have a quite different biological history than Senegambians or individuals in Central Africa. New Orleans is interesting because of a larger amount of non-African gene flow that occurred there as many Central Africans and Angolans were brought there. After a period of time in the US, especially in areas east of the Mississippi River, cotton became king. As opportunistic plantation owners changed the agricultural complex, there was no preference for specific ethnicities.

Here are some of the major slave ports in West Africa, from Senegal, Nigerian, Ghana and Angola. This is Gori Island, the cannons, the fort, the prison where the enslaved Africans were held. This is Fort Elmina, off the coast of Ghana, where the Gold Coast Africans were held. Initially, the Portuguese ran it, then the English came, conquered them, took it over, took over the economy, and took over the trade. It went back and forth; for a while the Dutch were involved. This is the door at the slave shipping port of Badagry on the coast of Southwest Nigeria. On the other side of this door is the ocean. Enslaved Africans were marched from the prison that they were housed in until the ships came to a small rowboat on the other side of the door and taken to the ship off shore. Badagry is now a museum, a tourist attraction. West Africans know the connection and the need and the interest of African-Americans who come to learn more about their ancestry. This young man runs the museum in Badagry. His great, great-grandfather was a king in that area and was responsible for enslaving many of his own people. The land, the museum and the artifacts were passed down to him. I gave him about 20 nira, about 20 cents, so that I could come look at the shackles and the chains.

Many things happened after the end of the slave trade. There was a change in where African-Americans lived in the US. In the early 1900s, with the industrial revolution, people wanted to get away from the plantations and go to urban areas to look for jobs. African-Americans in this area went up the Mississippi. In Missouri, Illinois, Indiana, and Michigan, we see clusters of black communities, all the way up into Pennsylvania and Virginia. These clusters of communities share their roots or their ancestry in the South. We use such information to study the genetics of diseases. When we recruit families to study prostate cancer in Detroit, Michigan, for example, we find that when we want their relatives, they often say, "My family is in Arkansas" or "My family is in the South." We trace their family lineages back down to this area. It's quite informative until there's a wall, and that wall is slavery. That's when the book was closed. Many of us feel our history starts here.

I asked some junior high and high school kids about their African-American history. Many of them put their heads down; they are ashamed because they think about slavery. That has been instilled in us, in our psychology. It's embedded in our consciousness that our people started as slaves. We know that's not true. One of the reasons that I work on this project is to provide some information that would be useful for going beyond that wall.

The 2000 census shows that despite the mass movement of African-Americans, that we are still pretty much where we were when we were brought here to the so-called crescent states: along the Mississippi River and in Louisiana, Georgia, South Carolina, North Carolina and Virginia.

Let's talk about some of the patterns of variation in African-American communities in the United States. This is a study with colleagues at Penn State University where we looked at a number of different African-American communities. In the urban areas, there are appreciable numbers or percentages of non-African genes. In the rural South, there is much less admixture because of the social norms of those communities. There are things that are taboo in rural Georgia that are not in New York, Chicago, or Seattle. The descendents of those matings are considered what, African-American? So, we continue to increase the genetic variation in our community due to that "definition" of an African-American.

Three major parts of West Africa are quite different genetically: Upper Guinea, Senegambia, Liberia, Sierra Leone; the Lower Guinea, Ghana and Nigeria; and Central Africa or Angola and the southern parts of Cameroon. The differentiated and diverse genetic markers that we look at provide some information in terms of ancestry. So let's talk about the science. To do this research, one needs informative DNA markers. DNA is compacted into what we call chromosomes. The Y-chromosome and mitochondrial DNA markers are useful for defining lineages. Y-chromosomes define paternal lineages. Mitochondrial DNA defines maternal lineages. Different areas of the chromosomes have genes, which are made up of four nucleotides that we call adenine, cytosine, thymine and guanine (A, C, T and G). They code for making proteins that allow us to function as human beings. They make nerves work to allow us to pull our hand away when fire is approaching. They enable a person to look at the person in front of you and say, 'his skin is lighter than mine.' All of the functions and manifestations that we see are coded by DNA in one-way or another. It's not 100% influence for each particular trait. In many situations, there are environmental and genetic contributions, but genetics are coded for by a sequence of A, C, T and G.

Polymorphism: poly means many and morph means form. Each gene can have many different sequences on its particular regions. That's what a polymorphism is. For instance, on a particular section of chromosome 1, 94% of the people have a C and 6% have a T. Most of these polymorphisms do not contribute to how one looks or acts or to a difference in disease. Some have a dramatic impact. In sickle-cell anemia, a single mutation on the beta hemoglobin gene causes a causes that catastrophic effect where red blood cells are sickle-shaped and cannot flow like they should. Cystic fibrosis in many European communities or Tay-Sachs are due to snips.

Why study maternal and paternal lineage? Let's take an individual; let's say that's me, Rick Kittles. I have 2 immediate ancestors from the previous generation, my mother and my father. We go back to my grandparents and it would be 4 ancestors, 2 generations back. You go 3 generations back it would be 8. If we go back 9 generations, 512 people have contributed to my genetic makeup. If we go back 350 years to the early part of the period of the enslavement of Africans, we are talking about 14 generations--16,000 ancestral parents. I find it neat that some of these lineages go back father to son, father to son; mother to daughter, mother to daughter. Those lineages provide an enormous amount of information. We can place them in certain situations, to certain populations, or certain regions of West and Central Africa. Sometimes we can do this unambiguously but there is a lot of information that we cannot assess. I've reconciled myself to that because, for the most part, many of us know nothing. For me, knowing something about my paternal lineage and my maternal lineage is a lot better than knowing nothing.

Mitochondrial DNA is maternally inherited. We look at the D-loop in mitochondrial DNA. It has about 400 base pairs of those nucleotides, those ATCG's. There is an enormous amount of information in that 400 base pair stretch that is structured by population history. If, for example a particular area of Ghana either expanded or dropped in population size, you'll see a DNA signature of that event. Even if it happened 500 or 1,000 years ago, you potentially could get that signature in the mitochondria DNA. It will be different than the signature that you see when you look at the Bamileke in Cameroon which has a different population history.

Sometimes populations come together or separate. You can see that too. Sometimes there are many sequences that are the same in two populations, and you'll notice that those populations speak the same language. You'll notice that those populations live across the creek from each other, so that says something about the history of those two groups is one of contact, sharing, cooperation or some form of interaction. Sometimes two populations are separated by a canyon or a mountain range and they're quite different culturally and genetically. So, anthropologists and geneticists have to work together to place the genetic information into context. We should not say "This is a marker for the Bamileke" and "This is a marker for the Ashanti." Those groups have particular histories and with those histories there's a genetic history as well.

Mitochondrial DNA is found in the mitochondria of cells, not the nucleus. Mitochondria make APT for energy. The mitochondrial DNA in any given cell are all genetically identical and it is passed from mother to daughter. The son inherits his mother's mitochondrial DNA but he can not pass it on. A brother and a sister will have the same mitochondria from the mother who got it from her mother but only the daughter can pass it on to her children.

I am going to quickly talk about mitochondrial DNA in Africa. I am going to use half of the data set that we have; it's 4000 individuals. These are populations from Western and Eastern Africa and we have three language families: Niger-Congo, Nile-Saharan and Afroasiatic. There are three major families or haploid groups or clusters of mitochondrial DNA from Africa. We call them L1, L2 and L3. A subset of L1 is pan-African. Another one is restricted to Western Africa. Then there's a rare group of haplotypes, these stretches of DNA. There's a rare cluster that's isolated in sub and in Central Africa. Then there's haplotype group L2, which is also pan-African. A subset is common among Senagambians on the Gold Coast. The third one is also pan-African and found in the Middle East also. L3 A is common in Eastern Africa. As a matter of fact, L3A is the ancestral sequence to the rest of the world. So if we were to look at the mitochondrial DNA of non-Africans, they will be a descendant of L3A. The oldest mitochondrial lineage is L1. It expanded about 100- to 150,000 years ago. We've dated the divergence or expansion of L3 to about 70- to 80,000 and L2 to about 60,000. These groups are clusters of related sequences. There aren't just three sequences in Africa, but there are three groups that cluster.

This is a map showing the distribution of those haplotype groups in Africa. Remember I said L3 was the one that was common in eastern Africa and it's the ancestral sequence for the rest of the world. You find it common here, and this is the likely path of the movement of people out of Africa in this area, too. This is the Middle East. You find mainly L3 there. This is Central Africa, very isolated, restricted, tropical rainforests. You just find L1 and L2. It's interesting that you see L3 of appreciable frequencies here in West Africa. It's the signature of the movement of people from East to West Africa, and it's likely also that there was an expansion of certain language families like Nilo-Saharan and Afroasiatic from the east to the west.

It's interesting that when we look at these communities of Africans that have L3, many of them are Muslims that speak Afroasiatic. So we see that this could be possibly linked to the movement or expansion of Islam. I say it could be; it's not definitive. I am giving you an explanation for why L3 is so high here. But I think all you guys see something here, right? Do you see anything here? [There's] nothing; there's no data. We know nothing about Central Africa south of Cameroon, Angola - nothing. That's the main reason why the African Ancestry Project is not providing a service at this moment, because we don't have one of the biggest areas of Africans that contributed to the Trans-Atlantic slave trade. 40% of enslaved Africans came from this region.
If I were a money-hungry person who just wanted to do this to make money, the project would have probably happened already. This is more than just prize and prestige. This is, to me, something very significant, socially and scientifically. So we've been working on that, getting this information and I'll go on.

There is a significant portion of the Y-chromosome that does not recombine or mix with any other chromosome. That part is inherited from father to son, clonally, meaning it's identical. It is inherited father to son, father to son. So just like the mitochondrial DNA, it would define paternal lineage. We have found that the history of males is not the same as the history of females in certain populations. In certain African populations, they're patriarchal; others are matriarchal. Depending on the culture, you find differences in the level of diversity for those markers, the maternal markers and the paternal markers. In some areas of Africa, there are only, what I call, two Y-chromosome types for all the males. There are just 2 chromosomes; they either have one or the other. Those are clans that have been established and centered around the male. You compare their Y-chromosome to the mitochondrial DNA, with the mitochondrial DNA there are hundreds and thousands of different types, but there are only two types of Y-chromosomes. In other situations where there are maternal lines, you could see something that's different, not as extreme as two mitochondrial DNA's, but you see lower levels than you see normally.

Somebody asked me yesterday, 'How do African-Americans reconcile finding out their paternal lineage isn't African but European?' I said, 'We know that already." So, it is not like we jump out the window or anything like that. Edward Ball wrote an excellent book Slaves in the Family. I turned it around: I have got some whites in the family. I've been saying this for a while, but now we've done the analysis and submitted it, 30% of African-American men possess Y-chromosomes or paternal lineages, which originate in Europe. I am one of them. This is largely due to the behavior of the slaveholders during the period of slavery in the US.

We know that every European male wasn't a slaveholder. From 2-10% of white males during that period in the US owned or had the opportunity to own slaves over their lifetime. Probably fewer had female slaves. Those who procreated with their enslaved African women servants were few. So if we do a study to find these European Y-chromosomes in the population now, many of them should be closely related because there were only but so many. I thinks Edward Ball in his book, estimated that he had over a hundred thousand African cousins because of the patriarch - I think he called him Redcap - who owned the plantation in Charleston. Redcap sired many "mulattos."

The X-chromosome, not the mitochondrial DNA, not the Y-chromosome has a gene called the antigen receptor. There are many studies looking at the markers in this small region. This small region has only 1,000 nucleotide base pairs compared to 3.5 billion base pairs. Even so, it is informative. We looked at almost 800 African-Americans in South Carolina and DC, some whites from Chicago, some Han Chinese, some Native Americans, and almost 1,000 West Africans, from Sierra Leone, Liberia, Senegal, Ghana and Nigeria. We looked at haplotype diversity, which is an estimate of the level of genetic diversity in the population. 0 is low, 1.0 is the highest. [inaudible tape] We looked at what we call the most common haplotypes, the stretch of DNA that is shared due to ancestry. When we look at the non-Africans, we see the same segment of DNA; it hasn't changed at all. European Americans, Asians and Amerindians all have the same haplotypes. We found two common haplotypes that were different in Columbia, South Carolina versus Charleston - Gullah, the same here. In Washington, DC there was a totally different mix of chromosomes. So, we see a very rich spectrum of diversity in African-Americans for that particular marker. Then we look at Africa, with five common haplotypes - Ghana, Nigeria, Nigeria, Liberia, Senegal, Sierra Leone which are cousins. They're almost identical, those two ethnic groups. I am sure something happened in the history of those two groups that led them to say I am a Mende and I am a Temne.

In the X-chromosome ancestry for this Columbia, South Carolina population, we found that 24% of those X-chromosomes shared ancestry with the Mende and Temne in Sierra Leone. 20% were due to gene flow from whites, 12% were from Mandinka, 8% from Ghana, the Congo, and 20% we couldn't place. I couldn't place them is because there was a lot of sharing across populations of those chromosomes. There is also a significant portion of populations that contributed to the slave trade that is not in the genetic database.

Let's get back to the publicly available genetic test for ancestry. Here are three groups: Oxford Ancestors, Brigham Young University and GeneTree. Oxford Ancestors says that they will test individuals in Europe, mainly Briton, and place their mitochondrial DNA in one of Seven Daughters of Eve clans. The Seven Daughters of Eve is a fable, a story. Bryan Sykes found seven clusters of mitochondrial DNA in and outside of Europe. So, he says give me your DNA and I will place you into one of these seven. When you get placed into one of those seven, there will be a story to accompany it. Europeans like to say something about how they're different, even though they're genetically really homogeneous. Brigham Young is sampling individuals saying that they're going to reconstruct the human tree. GeneTree does paternity testing.

The aims of the African Ancestry Project [http://www.africanancestry.com/about.html] is to establish a database of genetic lineages from indigenous West and Central African populations and ultimately provide a DNA-base test to determine West and Central African ancestry of African-Americans. It uses maternal mitochondrial DNA lineages and paternal lineages. It will be important that people who are interested in this know that I cannot tell you that you're 20% this and 20% that. It is these lineages and that's it.
I base the bulk of my identity around my paternal name, Kittles. Most, but not all, of our identities are based on surnames. Identity is multi-dimensional. It is experiences, how you were socialized, all of those aspects help you shape your identity. Genetics is not going to determine your identity but it is going to help you shape your own identity.

When I found out that my mitochondrial DNA went to Nigeria and I had the opportunity to go to Nigeria, it was very exciting. Some people may not want to do that. Almost 60-70% of the people don't want to go back to Africa, but those who do find it to be an enjoyable, exciting experience, something that helps to shape their identity. Your identity continues to be shaped. It's not something you're born with or you get when you hit puberty.
The database has almost 10,000 individuals representing 82 African populations. We need to sample Angola, Gabon and Nigeria.
Quickly, I'll go over some responses from the community. There are positive responses, there is apprehensiveness; there is skepticism that says that this is not needed at all and that we need to search for genes for disease. I agree that we need to search for genes for disease but part of a psychology of health and disease is based on identity. If this work can help craft that and shape that, it might even contribute to an understanding of health and diseases.

An individual came and wanted to get tested. This was early in the project when I was very naïve. I say that because you just cannot tell people this information and walk away. It is important to sit down and talk with these individuals. This man came, a big Afro-centric man, about 45, in African garb. He said, "I want to get tested to see where I fall in the database." He told me that his father told him something about his ancestry and his mother told him something. He wanted to confirm that. I ran the analysis and his paternal lineage was European, not African. His mitochondrial lineage was clustered with these Mandinka in Senegal and in Gambia. He came in and I gave him his results. I said, "Your paternal lineage is not African; it's European." He just froze. He froze, and then he sat down, quietly sat there. He did not say anything for 10 or 15 minutes. He said, "Are you sure?" I said, "Yes, we did the analysis. We ran it twice." He said, "Are you sure?" I said, "Yes, I am sure. I am positive."

His father told him that he was Mandinka. Many times we romanticize about these different African groups that we may have ancestry with. We don't have any knowledge, so we see Roots and we see the Mandinka and we say, OK, I am a Mandinka. So his father told him he was Mandinka on his side and his mother told him he was Mandinka on her side. After I told him that his father's side clustered in Europe, then he started thinking and said, "Well, what about my mother's side?" I said, "It was Mandinka, so she was right." He felt a little better but he was shattered. It scared me and I said to myself I'll never do that again. I'll never just sit and nonchalantly tell people these results because I had no idea of what his own perception of himself was and what he was told when he was younger growing up. So that was a major point in terms of my thinking about how to articulate this information to the community.