The African Genome Project - Why is it important ?

Lets take you on a journey as I rekindle my love for genetics, genomics and everything in between. This post explores what the human genome is, why it is important and why the African genome project is massive for science and medical research.

KEY WORDS

DNA: Letter code of instructions.

Gene: Genes are made up of DNA.

Genome: If your DNA was read out letter by letter, this is what makes up the genome.

Allele: is a different form of a gene .

Our DNA is what makes us who we are. It predicts our futures but also remembers our past.My first ever scicomm post was on genetics. I was tasked to write about the importance of DNA. I then found “The out of Africa” theory. In that post, I highlight how our DNA can be used to trace back our origins and show how humans migrated across the globe from Africa. The great human road trip.

I wrote that in my first year of university. Since then my understanding of science has grown and so have developments in genomic studies. A huge breakthrough in genomic studies was the completion of the human genome project. The human genome project started in October 1990 and ended in April 2003. The aim of this was to map out the genes. An amazing 15 year project led by scientists across the globe. It set out to completely write out all the letters and codes that make humans, humans. From that, further build and identify points that can help advance medical treatments and more.

Human genome project ( HGP) researchers deciphered the human genome in three major ways: determining the order, or "sequence," of all the bases in our genome's DNA; making maps that show the locations of genes for major sections of all our chromosomes; and producing what are called linkage maps, through which inherited traits (such as those for genetic disease) can be tracked over generations. - HGP website

What I hadn’t known before, your findings are only as good as your data set.The human genome project, an amazing task was not representative of African populations and for that reason the benefits would be skewed towards the “West” as with a lot of scientific advancements. Since the start of that project, there has been a rise of African researchers, finding and fixing holes in research. This article focuses on two points:

Understanding migration within Africa using genomic studies
Medical applications and the future of medicine with genomics

Understanding migration within Africa

Understanding our origins as Africans comes from piecing together migration patterns in early human development. Migration and human origins is a field already heavily studied by historians that can only further be supported by science. With a western lens, we focus on migration patterns leaving Africa, as of course that is relevant human origin for Europeans. For many Africans, migration within the continent is already studied by historians and archaeologists looking past borders created by slavery. The addition of science to history is beautiful to me as there isn’t a world or complete picture where disciplines don't intersect.

Bantu migration

The Bantu migration is a defining moment in human migration patterns. Historians have already mapped out through linguistics and archaeological studies theories on how this migration has occurred. Genomics and genome data analysis has been able to add to the findings.

In my first article about human migration, I explain how our DNA can be used to trace back our origins, specifically our mitochondrial DNA- that is only passed down maternally. In a study bringing together linguistics and genomics to understand Bantu migration, the findings support a “late” theory of migration pattern. In their study they use this method of mitochondrial analysis to try and understand migration patterns. Their findings indicate that migration and dispersal of bantu languages were due to the physical movement of people. This is known as demic diffusion.

To support demic diffusion, the genetic data would not have a lot of diversity, ie it would be easier to trace back to a single point. The authors state in their analysis “ lower genetic distances among Bantu populations when compared with those between Bantu and all the other major ethnolinguistic groups, as well as by the reduction of mitochondrial DNA and Y-chromosomal diversity proportional to the distance from the Bantu homeland. Furthermore, we found strong correlations between genetic and linguistic (as well as geographical) distances as additional evidence of a demic diffusion. “ - Bringing together linguistic and genetic evidence to test the Bantu expansion

Even with growing scientific evidence to support the diffusion Bantu migration theory of movement of people, there is still debate on the true nature of migration. Perfectly analysed in this review paper: Molecular Perspectives on the Bantu Expansion: A Synthesis . The authors breakdown the complexities in understanding migration patterns using DNA. Mitochondrial DNA is passed down maternally and therefore affected by maternal migration and mixing which will not directly reflect movement of certain populations as earlier generations and cultures adopt paternal languages. In the field, the alternative method for looking back using Y-chromosomal DNA. Y-chromosmal DNA represents paternal lineages. When Y-chromosomal DNA has been used, conflicting evidence of the mass movement of groups have been observed. The review paper highlights the conflicting evidence in the literature and gaps that need to be filled. Such gaps are complex and involve removing biases to confirm physical movement of people, understanding that data is limited and the findings as mentioned are only as good as the sources. Finally the assumption that pre-historical landscape is the same to what we have now can be a hindrance to interpretation of the findings.

Moving on from historical analysis, the run-off effects of such analysis and studies go deeper than looking back in time. As DNA can be used to infer timing of movements it can also be used to identify certain traits belonging to groups and regions. The ability of genomic analysis to do this is where its play into medical advancements becomes imperative.

A few relatable finding from : High depth African genomes informs human migration and health are:

Protection against severe malaria:Eleven single-nucleotide polymorphisms in G6PD associated with protection against severe malaria in heterozygotic female participants
Higher frequency of sickle cell mutation where malaria is prevalent: prevalent in East and West africa but nearly absent in South Africa. Using sickle cell disease specific mutations rs334; HbS; MIM 603903) was found at typically high allele frequencies in malaria-endemic west and east African populations.
Protection against parasitic infection but increased chance of being susceptible to a different parasite. For example APOL1 G1 and G2 provide protection against Trypanosoma brucei gambiense infection but also increase susceptibility to nephropathy in non-trypanosomiasis endemic areas, especially in the presence of HIV infection and were highest in west African populations.
Hypersensitivity to anti retroviral drug Abacavir found in other groups outside the Maasai of Kenya. Previously, the Maasai in Kinyawa, Kenya were the only African population noted to have an appreciable frequency of HLA-B*5701, which mediates hypersensitivity to the antiretroviral drug abacavir. In the expanded dataset, the allele was absent from west African populations, but observed at frequencies typically observed in populations of European or Asian ancestry.

Findings like this can help streamline and focus the advancements in science and medicine . The authors of the paper above looked at understudied populations from all the regions within Africa. They looked at gene flow within the groups. Where more differences meant more gene flow . Using points where the genes diverge can give you timestamps as to when populations became their own. Although susceptibility to a disease is not entirely genetic and some cases not at all, as environmental and socieconomic factors have a huge role in health and expression and progression of disease.

They were able to confirm and extend risk to disease using sickle cell, HIV, sleeping sickness. Comparing disease susceptibility or adverse reactions based on different populations. Adverse drug reactions are a huge area of research within the pharmaceutical industry as science moves away from generalised medicine and into personalised medicine. There won't always be variations in humans based on genetics but where there are, this can go into making better medicines for certain populations or focusing on most susceptible regions when it comes to certain treatments.

To wrap this up, genomics is an ever expanding field with the possibilities endless. It is the work of researchers that want to make a difference that makes this work exciting. Looking back at the article that sparked this blog post: Sequence three million genomes across Africa.

In this article researcher Ambroise Wonkam highlightshe gaps in the human genome project (HGP) and how H3Africa aims to extend the work by the (HGP). The importance of a more representative genome wide study comes with complications. With many African countries not having covered the basics when it comes to healthcare, genomics doesn’t seem as important. Governments may be blind to the potential benefits but their is overwhelming evidence of the gains that genomic medicine and scientific research will have on the continent. The use of developing scientific studies brings to the forefront new advancements and technologies and better access to healthcare services that are usually found elsewhere. The paper further highlights that, on bringing these studies, you give people access to better care that they wouldn't otherwise receive. Medical advancements and daily care go hand in hand.

there is still much to do to ensure that genomics works for the global public good. The focus on populations from high-income countries has come at the cost of understanding health and disease that might benefit the world. - Ambroise Wonkam