The Thousand Dollar Genome Has Arrived!

The first human genome was sequenced about a decade ago, at a cost of around four billion dollars. The results were amazing, showing us that people have a paltry twenty some thousand total genes. We thought we were a lot more complicated than that. We also found that chimps have DNA sequence about 99% identical to ours. Ouch again! We thought we were more special than that.

OK, we sequenced the human genome, and learned some cool stuff. So, you might think, end of story, now let’s do something else.

But the sequencing of one human genome is really just the beginning of the story. Different people have DNA sequences that are about 0.1% different. Unless they are twins. And twins are remarkably alike, in appearance and just about everything else, exactly because they share the same DNA sequence. The obvious conclusion is that your DNA sequence is really important in defining your many traits.

We’d like to be able to unravel the very complicated relationship between your DNA sequence and your traits. Many diseases have a foundation in DNA sequence. If we knew which of your genes contributed to your disease then we might be able to devise more effective therapies, designed to work best for you.

We’d like to sequence the DNAs of lots of people, with many different illnesses, to better understand the genetic basis of disease. But at four billion dollars per sequence that’s not going to happen.

Enter the DNA sequencing revolution! The cost of sequencing a person’s DNA has been plummeting. A year ago it cost only about four thousand dollars, down a million fold from the original four billion dollars. But even four thousand dollars is still a lot of money.

But, Illumina has just announced a new machine, the HiSeqX Ten, capable of sequencing a person’s DNA for only 800 dollars. Further, it offers staggering throughput, capable of sequencing tens of thousands of genomes per year.

The thousand dollar genome has long been considered the cost point at which genome sequencing can become a standard diagnostic procedure. We are now entering an era where everyone will have their DNA sequenced, and the resulting data will become a key part of our medical records.

As we collect thousands, and then millions of DNA sequences, and correlate them with the corresponding medical records, we will figure out how the different sequences contribute to disease. Medicine is about to take a giant step forward.

And, in a similar manner, we will begin to better understand how DNA sequences impact our other traits, including intelligence, appearance and athletic ability. When this new understanding is combined with our increasing power to manipulate our DNA sequences it opens up some fascinating, and perhaps frightening, possibilities. We will be the first species able to dictate our own evolution.

The term eveloce refers to a singularity boundary point in our evolution, where each generation is more intelligent, and better technologically equipped, to genetically design the next generation. A literal evolutionary explosion results.

And where this will take us, nobody knows. It could well mean the end of the human race as we know it, but perhaps the beginning of something better.

The Twenty Missing Genes

We people have about twenty five thousand genes, a shockingly small number considering how complicated we are. It is truly amazing that you can genetically encode all of the remarkable complexity of a person with only twenty five thousand genes.

As we sequenced the DNAs of other organisms we discovered that people don’t have a particularly large number of genes. Indeed, all mammals have almost exactly the same number as us, with the precise base sequences of the genes varying somewhat from one species to another. Several fish and amphibians actually have quite a few more genes than us.

Some of our twenty five thousand genes are of critical importance. If you inherit even a single bad copy of the Huntington’s disease gene, for example, then you are quite doomed. Certain regions of the brain will begin to die, usually in middle age, resulting in jerky involuntary movements and mental decline. There is a slow inexorable progression to dementia and death.

For most genes if you have one good and one bad copy then you are fine. But two bad copies can spell disaster. For example two bad copies of the HPRT gene causes Lesh-Nyhan syndrome, a horrible condition that includes self mutilation behaviors, with head banging, finger biting and lip biting. It is not unusual for people with Lesh-Nyhan to actually bite off their own lips and fingers.

The ongoing innovation in DNA sequencing is allowing us to learn more about the functions of specific genes. While the sequencing of the first human genome took many years and cost about four billion dollars, it is now possible to sequence a person’s DNA in a week or so, for under five thousand dollars. As a result we are collecting the DNA sequences of thousands of people, and before long it will be millions.

As we analyze these many DNA sequences and relate them to the features of the people they came from, including health and disease, intelligence, appearance and athletic ability, we will begin to crack the genotype/phenotype code. In time we will figure out which sequences cause which traits.

One of the early surprises from these types of studies is that we all carry a surprisingly large number of bad genes. A research article recently (Feb 2012) published in the prestigious journal “Science” describes “A systematic survey of loss of function variants in human protein-coding genes”. They examined the DNA sequences of 185 people, and found that on average a person has about 100 nonfunctional genes. And for about twenty of these genes both copies are “completely inactivated” by mutation. This is a bit of a shock, to realize that we are each of us walking around with about twenty completely dead genes, with both copies not working.

What does it mean? Well, for one thing it reminds us that not all genes are equally important. While some genes are critically important, there are clearly other genes that we can live without.

Nevertheless, it is unmistakable that we all carry a lot of genetic baggage. In addition to these completely nonfunctional genes we each have millions of SNPs, or single nucleotide polymorphisms, many of which can alter the functions of our genes, although not completely inactivate them.

It would seem that the way that we now make babies, although lots of fun, is really a game of Russian roulette. Bad gene combinations are probably the main reason why only about half of fertilized eggs actually make it to birth. Most of the rest die very early, before implantation into the wall of the uterus, and before the Mother even knew she was pregnant.

There is a perfect storm of ongoing revolutions in the fields of DNA sequencing, stem cells and genetic engineering that will soon allow us to take chance out of the equation. It will be possible to take skin cells and turn them into stem cells, and then to genetically engineer them to carry the DNA sequences that will produce the desired traits, including health, longevity, intelligence and appearance. Stem cells from the father can be turned into sperm, and those from the mother used to make an egg. The end result would be a designer genes baby, with a full set of functioning genes.

Such self-directed genetic engineering of our DNA could result in a dramatic and rapid transformation of our species. Indeed, it could mean the end of the human race as we know it, but perhaps the beginning of something better.

About the author:
Eveloce is a term coined by Steven Potter to stand for self accelerating evolution. It is derived from the words evolve and veloce, which is Italian for rapid. As we learn how to make smarter people, then those people will do an even better job of making still smarter people, and so on.
Steven Potter, PhD, is a professor at Children’s Hospital Medical Center in Cincinnati. He has published over one hundred research articles and co-authored the third edition of Larsen’s Human Embryology, a medical school textbook. He also wrote Designer genes: a new era in the evolution of man, published by Random House.