Waters et al.
Greenway et al.
ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis
Repping et al.
High mutation rates have driven extensive structural polymorphism among human Y chromosomes
Rohmann et al.
Mutations in different components of FGF signaling in LADD syndrome
Comments welcome.
I used to keep lists on post-it notes of books that I wanted to read in the near future. I would hold on to the list for some time, until it got crumpled and eventually vanished with all of the other pieces of paper that pass through your life. Then I would start a new list, with different books from the old list, which I had never gotten around to reading anyway. If you strung together the titles of all the books on the lists over the years that I haven’t read, you’d probably be able to fill a new book. I know I’m not alone in this because the writer Nick Hornby has a column in The Believer entitled “Stuff I’ve Been Reading,” which is accompanied each month by a list of “Books Bought” and a separate list of “Books Read”. The overlap between the two lists is minimal, and one can only imagine that Mr. Hornby’s book-free living space is getting smaller all the time.
In any event, here are some books that I’ve come across recently that seem list-worthy.
The first is No Two Alike, by Judith Harris, to be published in March. This is the follow-up to her controversial 1998 book, The Nurture Assumption, which argued that parents don’t influence how children turn out; genes and peers do (the perfect Mother’s Day gift, that one). According to Library Journal, No Two Alike “presents what may be the best personality theory since Sigmund Freud’s. Why do identical twins with the same genes and raised in the same household grow up with different personalities? According to Harris, adept brains and complex culture account for the difference”. The New York Sun has an early (positive) review.
From Garland Science, the publishers of Molecular Biology of the Cell, comes Robert Weinberg’s The Biology of Cancer, which aims to be the definitive textbook on the subject. As of early January, the author was busy cutting a 900-page manuscript down to 700-odd pages. Look for it in June.
New from Philip Reilly, CEO of Interleukin Genetics, and former member of the Board of Directors of the American Society of Human Genetics, is The Strongest Boy in the World. Published by Cold Spring Harbor, which published Reilly’s Abraham Lincoln’s DNA and Other Adventures in Genetics, the book is written for a general audience interested in the interplay of genetics with disease, ethics, and society. A wide range of topics is covered under this umbrella.
Genes in Conflict: The Biology of Selfish Genetic Elements by Austin Burt & Robert Trivers is a comprehensive, scholarly look at “the subject of selfish genetic elements in all its aspects, from molecular and genetic to behavioral and evolutionary”. It’s out from Harvard University Press, and you’ll find a review in an upcoming issue of Nature Genetics.
Our former editorial colleague here at the journal, Michael Stebbins, has written what is no doubt a lively account of controversial topics in science, entitled Sex Drugs & DNA (out in April from Macmillan). Mike has a varied background, and following his stint at NG he spent a year as a congressional fellow in the office of Senate minority leader Harry Reid. He now runs the Biosecurity Project at the Federation of American Scientists, where he keeps tabs on all sorts of nasty agents. You’ll find him blogging on biosecurity, and also on a wider range of topics. As for the latter, it’s well worth a visit—you won’t be bored.
Finally, in the world of fiction, and with impeccable timing, comes Allegra Goodman’s Intuition, out in a few days from Dial Press. Publisher’s Weekly sums it up:
In another quiet but powerful novel from Goodman (Kaaterskill Falls), a struggling cancer lab at Boston’s Philpott Institute becomes the stage for its researchers’ personalities and passions, and for the slippery definitions of freedom and responsibility in grant-driven American science. When the once-discredited R-7 virus, the project of playboy postdoc Cliff, seems to reduce cancerous tumors in mice, lab director Sandy Glass insists on publishing the preliminary results immediately, against the advice of his more cautious codirector, Marion Mendelssohn. The research team sees a glorious future ahead, but Robin, Cliff’s resentful ex-girlfriend and co-researcher, suspects that the findings are too good to be true and attempts to prove Cliff’s results are in error. The resulting inquiry spins out of control.
Those PW writers sure love the melodrama (cue the music!). Don’t let that put you off, however, because Goodman is the real thing as a novelist, and it’s rare when a writer of her talent tackles the lives of scientists.
Happy reading.
Park et al.
Zhang et al.
Long-range polony haplotyping of individual human chromosome molecules
Stephens et al.
Automating sequence-based detection and genotyping of SNPs from diploid samples
Comments welcome.
My first post to this blog noted the relative absence of blogging in the life sciences. Thanks to Notes from the Biomass for pointing out Postgenomic, a new aggregator that promises to be a very interesting way to track the growth of blogging in this area. Created by Stew at Flags and Lollipops, Postgenomic aggregates RSS feeds from life science blogs to give you an idea as to who is linking to which papers, and what they’re saying about them. Nature Genetics currently ranks third (after Nature and Science) in the list of journals that bloggers are linking to (I wonder if it’s all earwax and Abraham Lincoln?). I’ve put in a request to have Free Association added to the list of blogs (replete with rankings of ‘wordiness’ and links per post), and I’ve already come across several good ones that I’d never seen before. This bears watching.
Sato et al.
Feedback repression is required for mammalian circadian clock function
Ripperger & Schibler
Niihori et al.
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
Schubbert et al.
Germline KRAS mutations cause Noonan syndrome
Comments welcome.
Earlier today, The National Human Genome Research Institute and the National Institute of Environmental Health Sciences announced two new efforts aimed at identifying variants that underlie common disease. We will no doubt hear much more about them in coming months.
The two initiatives are the Genes and Environment Initiative (GEI) and the Genetic Association Information Network (GAIN). The GEI has a genotyping component and a technology development program aimed at generating new ways to monitor personal environmental exposures and their interactions with different genetic backgrounds. Several dozen common diseases are to be studied. Its proposed budget for fiscal year 2007 is $68 million.
GAIN will be managed by the non-profit Foundation for the NIH as a public-private partnership to carry out whole genome association studies using at least 375,000 SNPs for each of five common diseases. SNPs will be chosen from phase II HapMap data to include as many as possible from the Affymetrix 500K chip with r2 > 0.8, with a minor allele frequency > 0.05. The particular diseases and study populations will be determined through a peer review process. The private partners include Pfizer, which will contribute $15 million toward the cost of initial genotyping, to be carried out by Perlegen Sciences beginning in late summer, 2006 (Pfizer and Perlegen are already collaborating on such studies). Affymetrix will apparently be making a similar contribution. There is no indication that non-SNP-related variation (copy number or structural variation) will be assayed.
Hyperbolic language aside (“We stand on the threshold of creating a future that will revolutionize the practice of medicine…”) the promising structure of the program, and the fact that dedicated funds will be allocated during a time of a stagnant NIH budget overall, are both grounds for cautious optimism that robust associations will be found. It is a concern that no mention is made of potential overlap with whole genome association (WGA) studies that are already underway all over the map (that low, distant rumble you hear if you listen carefully enough). But on the other hand, a certain amount of overlap in the form of replicated associations in different populations is no doubt ideal.
Of particular interest are the data analysis procedures in place, given that assessing statistical robustness in whole genome association (WGA) studies remains almost as much an art as a science. Each PI, and an analyst they designate, will be required to attend a workshop on analysis of WGA data, which will open to other members of the community. As stated on the GAIN website:
The goals of the workshop will be to review current experience with WGA studies completed or in progress to:1) identify particularly powerful designs and methods of analysis for WGA studies; 2) identify potential pitfalls in design and analysis of WGA studies and ways of avoiding them; 3) propose new approaches to WGA data analysis, and design or analysis modifications needed to implement them; and 4) identify needs for methodological development in design and analysis of WGA data.
And, equally important:
A key role for the Analysis Working Group will be to suggest analyses to be conducted across multiple projects, as appropriate, and common approaches to analyses within each project as needed to enhance comparability.
We, and others, (and many others), have been grappling with this very issue. Having seen more than a few disagreements between experts over the appropriate statistical standards to apply, one suspects this meeting of the minds may be painfully difficult.
But, alas, no pain, no GAIN.
Murdoch et al.
Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans
Williamson et al.
Yi et al.
Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs
Mak et al.
Polygenic control of Caenorhabditis elegans fat storage
Comments welcome.
You may be aware of the recent story out of Austria, which culminated in the documentary “Mozart: The Search for Evidence,” on an ancient skull purported to be that of Mozart. DNA tests on the skull, which has been in the possession of the International Mozarteum Foundation in Salzburg, were inconclusive, as the tested skeletal remains thought to be that of Mozart’s maternal grandmother and niece turned out to be unrelated to each other, making any inference about the ‘Mozart’ skull impossible (you’d think they would get the result first, before committing to a TV documentary, but that’s another issue). In a recent op-ed piece in The New York Times, novelist Richard Powers notes that the remains of Mozart and Beethoven have been probed for years in hopes of learning something new about their life histories and their deaths. Powers comments:
Diagnosing art’s unsolved mysteries with state-of-the-art medical knowledge is irresistible….But what can the bones know that the notes don’t? Forget the forensics and face the music. The mysteries hidden in Mozart’s skull are everywhere for the hearing.
Agreed. And yet…
Human transmission genetics, by definition, is the study of history. All of this came to mind upon the recent publication in Nature Genetics by Ikeda et al. of the mutation underlying spinocerebellar ataxia type 5, a form of ataxia quite common in the descendents of Abraham Lincoln. This is far from the first time that the search for genetic disorders in Lincoln’s pedigree has been at issue. But in addition to advancing research in ataxia, it surely would be of more than passing interest if the 16th president of the United States were affected with ataxia, even if our appreciation of the Gettysburg and second inaugural addresses remain unchanged.
The senior author of the paper, Laura Ranum, comments on the 13-year-long search for the SCA5 gene:
In 1992 I received a phone call from a neurologist with an ataxia patient that had a strong family history of the disease. Impressed upon hearing there were at least eight affected family members, I asked if I could contact the patient directly. After talking to this woman about her family history she paused and said “but you know, you really ought to talk to my mother…I think she knows of some more cousins”; the SCA5 odyssey began. I called her mother, then her mother’s cousins, and their cousins. A common theme of these calls was that these family members all knew that they were related to President Lincoln, but not necessarily how they were related to each other or that there was so much ataxia in the family. After obtaining a few DNA samples and ruling out the SCA1 locus, Dr. Larry Schut, a neurologist working at the University of Minnesota, and I traveled to visit the family. Family members were very proactive, wanting to find the source of what they called “Lincoln’s disease”, and invited us into their communities and to family reunions, where we performed neurological evaluations and collected blood samples. Eager to brag about the family connection to Lincoln and also to increase awareness of ataxia, a family member arranged for the local newspaper to do an article about our research on our second of many trips. Although at the time we didn’t know that the disease went back as far as President Lincoln’s grandparents, because at that time we were only working with the branch of the family descended from President Lincoln’s uncle Josiah, the reporter wrote that we had traced the gene back to President Lincoln’s grandfather, Captain Abraham Lincoln. Embarrassing at the time, this inaccuracy proved serendipitous and fortunate because I was soon contacted by descendents of President Lincoln’s aunt Mary, who also suffer from ataxia. Dr. Schut and I went out to collect this branch of the family. Using DNA from both branches of the Lincoln family, we mapped the ataxia gene to the centromeric region of chromosome 11, a novel ataxia locus. The disease was designated spinocerebellar ataxia type 5 and the results were published in 1994 in Nature Genetics.
Although we had collected DNA from a considerable number of family members, we had very few recombinants because of the suppressed recombination near the centromere, and so our gene-rich critical region remained frustratingly large. Over the next decade, we continued to work with both branches of the Lincoln family, taking field trips almost annually—in what seemed to be an eternal search for the “key” recombinant. Dr. John Day joined the research effort in 1996, as part of an ongoing collaboration involving SCA8 and myotonic dystrophy type 2. Over the ensuing years, with many trips to examine family members and refine the clinical features of SCA5 we were able to collect and examine 299 family members, including 90 affected individuals with this slowly progressive neurodegenerative disorder.