DNA and You

If You Think Wired Is a Good Place to Go for Medical Advice, Think Again...

Andrew Yates at Think Gene wrote today about the new Wired Wiki home genomics how-to guide, "Check Yourself for Genomic Abnormalities."  Check out Andrew's post for a great discussion of the maturity, or, rather, the lack thereof, of the personal genomics market.

Something caught my eye though as I read through "Check Yourself for Genomic Abnormalities" at the Wired Wiki site.  The wiki post describes several options for "checking yourself for genomic abnormalities": 1) Visit a Genetic Counselor; 2) Scan Your Whole Genome; and 3) Perform Lab Tests at Home. 

Interestingly, the author(s), who otherwise did an ok job of briefly explaining what genetic counselors do, utilized consideration of a diagnosis of celiac sprue as an example of a situation in which someone would want to see a genetic counselor rather than "scanning their whole genome" or "performing lab tests at home."

I think the world of Wired, but in case it is not clear to the early adopters out there...

Wired is probably not where you want to get your medical advice.

Celiac disease (aka gluten-sensitive enteropathy or non-tropical sprue), the condition mentioned in the hypothetical scenario, is diagnosed via a blood antibody test and small intestinal biopsies.  Thus, rather than seeing your local genetic counselor if you think you might have CD, you would do well to discuss it with your primary care doctor and a gastroenterologist. 

The wiki writer's confusion likely stems from the fact that genetic factors do play a role in risk for Celiac disease; however, the genetics are complex, and the genes involved are not deterministic.  For example, risk of Celiac disease is higher if you have certain forms ("alleles") of HLA genes.  About 30% of the population has one of the Celiac disease-associated HLA alleles; however, only 3% of individuals with the Celiac disease-associated allele develop CD.

Music and Your Genes: One Step Closer to Understanding the Biological Basis of Musical Ability

We've all come across certain people who seem to have a particularly high ability to play and/or appreciate music.  As a geneticist, my assumption has always been that this is inherent and heritable to some degree.  Nevertheless, it could certainly be argued that it is environmental. 

The literature provides some support for the concept that musical ability is genetic.  For example, musical talent has been noted to cluster in some families.  Additionally, the ability to identify pitch in the absence of a reference pitch clusters in families, as well.  Conversely, tone deafness, also known as congenital amusia, also seems to be genetic on the basis of strong familial clustering.  Lastly, in a formal study of pitch recognition in twins, the heritability of scores on the so-called Distorted Tunes Test were estimated to be more than 70%.

Now, a Finnish research group has demonstrated that it is highly likely that a gene on chromosome 4 (located in the vicinity of chromosome band 4q22) influences musical aptitude.  They utilized three different measures of musical aptitude in coming to this conclusion and performed a "genome-wide linkage test."  This study has narrowed the region containing the gene to a segment of the chromosome containing ~50 genes, so further studies will be necessary to find the precise genetic change influencing musical aptitude in these families. The authors also noted other regions of the genome in which there was suggestive linkage, suggesting that musical aptitude is likely to be affected by multiple genes.  It will be interesting to watch as these are hopefully identified in future studies.

Reference

K Pulli et al.  Genome-wide linkage scan for loci of musical aptitude in Finnish families: evidence for a major locus at 4q22.  Journal of Medical Genetics 45: 451-6, 2008. 

Voices of the Infertile in the NY Times

Infertility, which in some cases can have a genetic cause, is a challenging obstacle for many couples.  A recent article by Karen Barrow, in the NY Times, focuses on the challenges faced by couples unable to conceive. 

An interactive feature associated with the article features the voices of several of women interviewed.

Rett Syndrome on Fox Show: "So You Think You Can Dance"

Tara Parker-Pope of the NY Times writes about an episode of the Fox reality show, "So You Think You Can Dance," in which Rett syndrome was featured.

For more on Rett Syndrome:

Rett Syndrome (MECP2-Related Disorders) GeneReview

International Rett Syndrome Foundation

Mandatory Waistline Measurement in Japan: Good Public Health Social Policy? Or Genetic Discrimination Against Fat People?

The NY Times has a really interesting piece on a new policy of mandatory waistline measurement in Japan.  With a goal of improving the public health, the government has established a state prescribed limit on male waistlines of 33.5 inches along with a limit of 35.4 inches for women...

No...I'm really not kidding.

Companies and local governments will apparently be required - under this new national law - to measure waistlines of those 40-74 years old during annual checkups.  Apparently, those not meeting the country's standard will be given dieting guidance if they do not meet the standard and do not lose the weight over 3 months (with subsequent escalation of the scrutiny and advice if folks are still too rotund at 6 months). 

Interestingly, the Japanese government intends to impose monetary penalties on entities (local governments and companies that fail to meet specific targets).

Although I am sure that the Japanese government has good intentions, this is a very interesting policy in light of the fact that obesity is a trait that can only be partially modified by behavioral change.  In other words, it is clear that obesity risk is to some extent a heritable trait, determined to some extent by one's genetic background, that can be difficult for some individuals to overcome.

Although this is an interesting and aggressive experiment aimed at reducing healthcare costs, it has the potential to result in further stigmatization of those affected by the obesity epidemic (something that is, no doubt, intended by the rule since it may result in public health benefits).  By imposing penalties on local governments and companies, the government is avoiding the appearance of discriminating against those with generous waistlines; however, this will create tremendous incentives on these entities to exert considerable pressure on individuals whose waists are over the limits. 

In sum, it's a bold social policy.  It may help with healthcare costs in the long-run, but is it genetic discrimination? 

What do you think?

Henry Louis Gates, Jr. Interviews James Watson at The Root

Kudos to my girlfriend for pointing me in the direction of this one.  It's worth a look:

• A conversation between Henry Louis Gates, Jr. and James Watson.
• An essay by Henry Louis Gates, Jr. about the interview: "The Science of Racism"
• Video from the interview.

What do you all think?

Is it heritable? A new series on twin studies.

Twin studies are one of the foundations of modern human genetics.  Researchers take advantage of a basic biological fact (that identical or monozygotic twins share essentially 100% of their genomes while fraternal or dizygotic twins share 50%) to study to what degree certain traits (disease risk, etc.) are heritable (i.e., how much of the disease risk is conferred by the genes versus the environment or just random events). 

Twin studies offer a very interesting window into human genetics and can often be extremely thought-provoking.  Here at DNA and You, I will periodically point out an interesting twin study as food for thought.

For example, it is commonly assumed that any familial effect on political party choice is environmental in nature, but these authors set out to look into this in further detail.  Basically the results suggest that although there is a modest effect of genetics on political party choice, this is probably conferred through intermediate genetic influences on attitudes about key political debates and other things like church attendance and social class.

Genetics Takes Over The New England Journal of Medicine

One only has to briefly scan the table of contents of tomorrow's issue (Jan. 10) of The New England Journal of Medicine to figure out that 2008 is going to be a big year at the crux of genetics and medicine!  The issue includes the following (note that only a subset of the following full articles are available without subscription):

• A perspective by Drs. David Hunter, Muin Khoury, and Jeffrey Drazen on the medical implications - or lack thereof - of personalized genotyping services (i.e., 23andMe, Navigenics, and deCodeMe).  More on this in a follow-up post later this evening.  However, I can tell you that these three are not fans of personalized genotyping companies.  There is also an audio interview with Dr. Khoury available here.
• Dr. John Bissler and colleagues from Cincinnati Children's Hospital Medical Center present the results of a study of sirolimus treatment of angiomyolipomas in tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis.  TSC is a Mendelian genetic disease in which the genetic defects lead to constitutive activation of the "mammalian target of rapamycin" (mTOR, a key cellular signaling pathway intermediate).  As sirolimus suppresses signaling through mTOR, this study represents a rational use of sirolimus to treat angiomyolipomas in TSC.  More on this soon at my other blog, Cancer and Your Genes.
• Dr. Antonio Pelliccia and colleagues present the results of a study looking at implications of EKG abnormalities referred to as "repolarization abnormalities."  They show that out of 81 athletes with a particular type of EKG abnormality (see free full text here for details), 5 (6%) ultimately developed cardiomyopathies (including one individual who died from arrhythmogenic right ventricular cardiomyopathy - which has a genetic basis). 
• Dr. Melanie Percy and colleagues demonstrate that an oxygen sensing gene called HIF2A is mutated in a family with Familial Erythrocytosis (i.e., a heritable condition in which affected individuals have too many red blood cells).
• There is also a review of the book, "Reprogenetics: Law, Policy, and Ethical Issues," edited by Lori P. Knowles and Gregory E. Kaebnick.
• As if all that were not enough, an article in the NEJM "Clinical Problem" series focuses on the approach to Long QT syndrome, an inherited, genetically heterogeneous condition that predisposes individuals to life-threatening arrhthymias (abnormal heart rhythms). 
• Last, but certainly not least, in an online article published today, Mark Daly and colleagues report the identification of a small, sub-microscopic region of chromosome 16 that when deleted or duplicated leads to autism susceptibility!  Although this is probably only responsible for about 1% or so of cases, this is a huge accomplishment.

In looking at just this single issue of NEJM, I think it is safe to say that we have a very interesting year ahead of us.  Stay tuned to DNA and You for more detailed posts on the above!

Donor Sperm and Genetic Disease...Again

Bertalan Mesko at ScienceRoll linked today to a Wall Street Journal Health blog post about a child with Tay-Sachs conceived with a donated egg.  This interesting story, originally reported in the LA Times, certainly isn't the first example of a rare genetic condition being passed on to a child via a donor egg or sperm.

For example, in 2006, Dr. Laurence Boxer of the University of Michigan and colleagues demonstrated that donor sperm from the same individual transmitted a mutation in the ELA2 gene to 5 separate children, giving them a condition called severe congenital neutropenia.  Children with SCN do not make enough neutrophils (a type of white blood cell that fights off bacterial and other infections).

The original report and news coverage (for example here) question whether mechanisms to identify clusters of genetic disease transmitted by single donors should be implemented.

NY Times Personalized Genomics Feedback

For those who haven't seen it yet, a series of letters responding to the NY Times coverage of 23andMe, Navigenics, and deCODE Genetics are available here.

Interestingly, the author of the last letter in the NY Times series, Dr. Hugh Rienhoff, has made some news himself of late.