Not surprisingly, there has been intense interest in the genetics of obesity in recent years.  Obesity is a major health problem, resulting in tens of thousands of premature deaths and billions of dollars in healthcare costs each year in the United States, and it is known from twin and family studies that weight is a highly heritable trait.

The genetic mutations and variations identified so far explain only a small percentage of the variability in body mass seen in the population.  Some exciting clues have been found, however, as to why some people are more prone to obesity than others and how this might be counteracted.  But new research, published online this week in the American Journal of Human Genetics, shows that caution must be taken in moving from genetic discoveries to drug development.

Variations in the FTO gene have consistently been associated with obesity. On average, people who carry two copies of the “risky” version of this gene weigh six to eight pounds more than those who carry none. Mice completely lacking the FTO gene were shown to be leaner than their normal littermates, despite being less active.  These results have led some to suggest that inhibiting the FTO protein with a drug could be a good for obesity treatment or prevention.

(23andMe customers can see their FTO data in the Obesity Research Report.)

But an international team of researchers led by Sarah Boissel of the Université Paris Descartes in France has found that a mutation that interferes with the function of the FTO protein is associated with a lethal genetic condition.  Members of a large, inbred Palestinian family born with two copies of this mutation had multiple developmental abnormalities and died before the age of three.  Based on their results, Boissel and her colleagues warn that any research exploring the use of FTO inhibitors as obesity treatments must include a “careful assessment” of the potential to cause birth defects and other toxic side effects.

More about FTO:

SNPwatch: Gene Variant Linked to Obesity Affects Food Choices in Children

It’s Not Genes or Environment, It’s Genes AND Environment

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It’s not enough to teach genetics, says Michael Dougherty, director of education for the American Society for Human Genetics.  It has to be taught in the right way.

“Current teaching practices may be producing a public that is unprepared to participate effectively as medical consumers in a world where personalized medicine will rely increasingly on genetic testing, risk assessment, predispositions, and ranges of treatment options that include biological and behavioral components,” writes Dougherty in an opinion piece published online today in the American Journal of Human Genetics.

Dougherty calls for curriculum reform at all levels, from middle school all the way up through undergraduate education. The key, he says, is for students to understand that the genetics of most human traits and conditions are complex and, with only rare exceptions, not deterministic.

Dougherty suggests a new genetics curriculum that begins with lessons on traits that show continuous variation, such as height and weight, and focuses on how multiple inherited and environmental factors can affect these traits.  Teachers could then move on to discussions of genes and the molecular details of how they are passed from generation to generation.  Only here, in the later stages of their genetics education, would students learn about the rare single gene diseases, such as cystic fibrosis and PKU, that make up the bulk of today’s genetics lessons.

“Our incompleteness of understanding and the messiness of complex-trait examples are poor arguments for maintaining the status quo in our genetics classrooms.  We know on theoretical grounds that the entirety of phenotype is defined by genes and environment, and substantial uncertainty still characterizes both.  To pretend such uncertainty does not exist is to deprive students of an appreciation of both modern genetics and the nature of science.”

Dougherty points to the Genes, Environment and Human Behavior module, funded by the Department of Energy and available from BSCS, as an example of the kind of lesson that could help correct the misconceptions that students already have.  The National Human Genome Research Institute also has available a Human Genetic Variation curriculum supplement.  And of course, you can always check out the Genetics 101 section of the 23andMe website for a basic introduction to genetics.

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A paper published in the April issue of the American Journal of Human Genetics shows that two major events in the history of religion – the spread of Islam and the Crusades – have left their mark on Lebanon’s male population.

The authors of the AJHG paper showed that a disproportionate percentage of Muslim men in Lebanon have Y-chromosomes of a type that is common on the Arabian peninsula. Migrants from Arabia brought Islam to Lebanon during the 7th century.

Similarly, a disproportionate number of Lebanese Christian and Druze men have Y-chromosomes similar to those found in western Europe. In fact, the most common Y-chromosome signature in Lebanon is most abundant in France, Spain, northern Italy and the Low Countries. But it is found nowhere else east of Hungary.

The authors of the AJHG paper attribute that remarkable genetic connection to the Crusades, a series of military campaigns by European invaders against Jerusalem and other cities of religious significance in the Near East.

There is also an indication that men from Turkey introduced their genes into the Lebanese population during the time of the Ottoman Empire, which ruled Lebanon from the 16th to 20th centuries.

In most countries, geography is the most significant factor influencing the genetic variability of the population. But in Lebanon, religion accounts for more than three times as much genetic variation as geography.

“Such structure might arise only when several unusual criteria are met,” the AJHG paper concludes. “Migrations based on religion must take place between areas with different representative Y-chromosomal types, and they must establish genetically differentiated communities that remain stable over long time periods. In Lebanon, these conditions appear to have been met for over 1,300 years.”

“The Siege of Acre” by Dominique Louis Papety (1815-1849)

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