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A Short Guide to the Human Genome

Author: Stewart Scherer

Publisher: Cold Spring Harbor Laboratory Press

Read: (yes | maybe | no)

“A Short Guide to the Human Genome” (or SGHG) is a book by scientists, for scientists. It’s not for laypeople, and while condensed, it’s an advanced text best read by molecular biologists comfortable reading scientific papers about genomics. For this, SGHG is a “maybe” read.

But, as a useful book for scientists, SGHG is quite good. Laudably, its stated purpose is to present facts to flesh academic work. With its simple question-to-answer format and well-summarized tables and graphs, it does so well —without sacrificing scientific thoroughness. However, don’t expect any explanations, editorial insights, or appeals to the “bigger picture.” Which Genes Have the Most Exons? Scherer states the facts: TTN has the most exons. It has 312 exons. You are expected to provide your own context.

This book is for you if:

• You need to pepper your powerpoint presentation with “relevant interesting facts” about the genome. In fact, if you teach a university lecture about genetics or molecular biology, BUY THIS BOOK. You will not regret it, and your lectures will be better for it.
• You have or may ever write a scientific paper with a string of “ATCG” anywhere in the text.
• You are a huge nerd for factiods, and hey, you read all those journals anyways…

This book is NOT for you if:

• You find Nature Genetics to be unintelligible.
• You find Nature Genetics to be uninteresting.
• You’re James Watson.

I eagerly anticipate the contents of this book to appear on Wikipedia.

Fun Genome Facts!

(see? You can’t resist peppering your work with these snackable factiods. Just think how easy this could make your work when you need some plug-and-play ideas?)

• The blood type of reference human genome is “O” (pg. 135)
• A mouse has 19 autosomes, plus the XY sex chromosomes. While similar, its genome is about 10% smaller than a human’s. (pg. 146)
• The Y chromosome is by far the least sequenced chromosome, with only 44.4% sequenced (as of release 36.2). This is because the Y chromosome contains large blocks of repeated sequences, and the “shotgun” approach to used to sequence the reference human genome does not resolve repeated sequences accurately. (pg. 6)
• How big is the largest protein? 33,423 amino acids (titin, which is encoded by the TTN gene). The smallest? 25aa (product of gene RPL41). The smallest predicted? 13aa (LOC644929 and LOC727721). (pg. 68)

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Andrew: Microbes are everywhere, so a coping mechanism to survive in a world of bacteria seems evolutionary necessary. We traditionally consider our “anti-non-self ” immune system as that coping mechanism, but organisms may have also evolved a system of stable microbial coexistence. How? By inter-species gene regulation.

This is particularly interesting to me because it shows how genomics isn’t about closed, procedural, self-describing systems. Rather, genomics is contextual, recursive, and non-deterministic, like how DNA is part of the phenotype described by the genotype described by that DNA. Even better, the confusion isn’t limited to a single organism’s genome: here, squid genomic expression is modified by symbiotic bacteria to create an stable environment for the microbes and a novel phenotypic advantage for organism. So, evolutionary selection may act not only on what potential phenotypes a genome describes itself, but how that genome may be expressed as influenced by the expression of other organisms’ genomes and the environment.

…And you want to go back to “genes determine traits?” Boring!

Though bacteria are everywhere — from the air we breathe and the food we eat to our guts and skin — the vast majority are innocuous or even beneficial, and only a handful pose any threat to us. What distinguishes a welcome microbial guest from an unwanted intruder?

Research from the University of Wisconsin-Madison suggests the answer lies not with the bacteria, but with the host.

A study appearing online this week in the Proceedings of the National Academy of Sciences may help reveal what sets a platonic relationship apart from a pathogenic one. In the paper, researchers from the UW-Madison School of Medicine and Public Health and the University of Iowa identify a slew of microbe-induced genetic changes in a tiny squid, including a set of evolutionarily conserved genes that may hold the secrets to developing a mutually beneficial relationship.

“Interactions of animals with their microbiota have a profound impact on their gene expression, and to create a stable association with a microorganism requires a lot of conversation between the microbe and the host,” says UW-Madison medical microbiologist Margaret McFall-Ngai, senior author of the new study. … Continue Reading »

Eppendorf International, a lab equipment supplier, created this video to promote their automated pipetting machine. No commentary necessary… though we’d like to reward efforts like this with a relevant, organic blog links.

No. Why?

1. It’s not direct to consumer (DTC), it’s through physicians.
2. It’s a service business, not a product business. (Helix Health’s Services page)

Helix’s non-classification as a competitor isn’t a slight, it merely does not compare well with Navigenics, 23andMe, and deCODEme because it sells services (time), not product.

unit profit by size of business

consulting begins profitable, but becomes unwieldy at scale
products require significant capital to develop, but yields huge returns (scale * profit) if it can scale

Services business begin profitable at full capacity (because people do not work at a loss) but do not scale well because experts have limited time to sell. So consulting businesses like Helix Health may achieve consistent, moderate returns, but they don’t have the potential for monopolistic growth that leads to huge exits. Thus, consulting businesses rarely raise venture capital funding which depend on a few huge exits before their fund’s horizon for profitability.

So deCODEme, Navigenics, and 23andMe are “all or nothing” fence-swingers, while Helix Health is not. So the “crossing the chasm” argument applies less to Helix because its survival doesn’t depend on reaching a general market.

Bottom line: if every American ordered a 23andMe test, 23andMe would be Google. If every American tried to schedule an appointment at Helix Health, there would be a very long line.

23andMe has the most will to succeed, followed by Navigenics, followed by deCODEme. All three have sufficient potential funding, so will (and luck) will most decide who will survive The Chasm.

Yesterday, I mentioned a popular business graph called “The Chasm.” The Chasm is start-up business jargon for the difficultly businesses tend to experience growing from a market of early adopters to the general public. This is because customer motivation changes: early adopters buy because they like new technology, but most people buy because they want to solve problems with minimal effort.

Today, DTC (direct to consumer) genomics is still in its “innovators” market phase, though continued coverage in Wired and regulatory attention suggests that the market is approaching an “early adopter” transition. But which genomics start-ups will survive to cross The Chasm to reap the riches of a greater market?

Two factors keep start-ups alive during tough times:

1. Funding: No money, no payroll, no people. Start-ups, particularly venture-funded start-ups, are profitable until they are bigger, more mature companies.
2. Will: How much does a start-up want to succeed, and what do will its leaders lose if it doest? Does your company have the morale and reputation to recruit talent and investment to beat the competition, weather setbacks, and persist through regulatory struggles?

Consider the “big three” DTC start-ups: 23andMe, deCODEme, and Navigenics. Other competitors are possible, but identifying them is speculation. Further, the recent California “legal lab” crackdown seems to have scared away most other scrappier competitors for now.

I think that all three competitors have ample funding… if they have the will to spend it. I argue that 23andMe and Navigenics have that will, while deCODEme may or may not.

The leaders of 23andMe and Navigenics are most personally and publicly invested in the success of their ventures and thus are most likely to succeed. 23andMe wins the accountability metric because if it doesn’t succeed, it will forever be known as “that Google’s wife’s start-up toy with that disgruntled affy chick.” These women probably do not appreciate being known as such, and are powerful and determined enough to prove otherwise. That alone will keep 23andMe around indefinitely. The rest of the 23andMe team is also well featured on the about page. However, the iStockPhoto slideshow on the 23andMe team page needs replacing.

Navigenics team is also very well featured, even better than 23andMe’s team.

At deCODEme, Kári Stefánsson may publicly represent the business, but he’s the CEO of deCODE. Who is personally accountable for the success of deCODEme itself? On both the old and the new versions of the deCODEme website, nobody is named. The new About deCODEme page does feature a photo of the deCODEme team, but the only names are of deCODE researchers publishing papers, not deCODEme management. (they are pretty nice photos, though)

Further, both 23andMe and Navigenics feature recruitment on their websites and actively advertise positions with third parties (a quick Google search confirms this). deCODEme does not.

Finally, deCODEme’s parent company, deCODE, has not been doing well financially and has never reported a profit. It has recently eliminated many positions, is debt-leveraged, has sold-and-leased its American office, it’s stock price is at $1 and cents from about $28 in 2000, and its CEO has warned of ending operations. All of this is bad for morale, and if more cuts must be made, an unprofitable deCODEme is a likely candidate. I doubt deCODEme will ever be eliminated because it’s obviously Kári’s personal initiative, and as far as I can tell, deCODE is Kári. What’s most likely, if things get bad, is that deCODEme will process orders, but languish without growth or direction as 23andMe, Navigenics, and other competitors continue to hire, grow, and improve.

… Continue Reading »

Two weeks ago, we alluded how one could run one’s own genetic tests.

Now, Wired has grabbed the gene baton and has launched a home genomics how-to guide: Check Yourself for Genetic Abnormalities.

Wired is the banner publication of everything early adopter, but don’t expect much early adoption yet: the day belongs to the scrappy hobbyist innovators. Hobbyists are noisy, and they are more than the few wealthy patrons of yesterday’s DTC (direct to consumer) genomics market, but hobbyists are also notoriously frugal. I predict a flat revenue time-of-trials for DTC genomic start-ups amid a boom of grassroots interest until a bigger market meets a falling price.

The famous market graph from Crossing the Chasm, a staple read in any technology start up or MBA program. DTC genomics is still in its enthusiasts phase, though Wired articles suggest market movement towards early adopters.

Worse, as the graph above suggests, this is merely the first market barrier for genomics. The real business challenge lies between the pre-interested and everybody else. Who of the big three DTC genomics start-ups will survive years of meager profits to consistent losses in this slowing economy and hostile American regulatory environment?

We’ll publish a more in-depth how-to soon. Our goal is that with our guide, the average enthusiast will be able to conduct at least one hobby genomics test. Perhaps, in our own small way, we’ll help the industry by rushing the bloom of geepy*, techcrunch-y publicity into an early harvest of paying customers.

*geepy: adj. “geek cheap,” or of how the well-to-do geek considers paying for new technology an engineering challenge to be surmounted, even at great inconvenience, time, and effort