Category Archives: Genetics

Time bomb – revisited

I revisited a 2005 paper on “Folic acid – vitamin and panacea or genetic genetic time bomb“. From the abstract: “We live in a health-conscious age — many of us supplement our diet with essential micronutrients … so-called ‘functional foods’ … We examine this issue in relation to the B-group vitamin folic acid, and ask whether supplementation with this vitamin could introduce a strong genetic selection pressure…” As I found this paper highly interesting, here is my analysis, how the story goes on:

  1. Martinez-Frias, ML. Folic acid: a public-health challenge. LANCET.
  2. Kafadar, AM. C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas. ANTICANCER RESEARCH.
  3. Kelemen, LE. The role of folate receptor alpha in cancer development, progression and treatment: Cause, consequence or innocent bystander?. INTERNATIONAL JOURNAL OF CANCER.
  4. Nazarenko, MS. Frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene at the early stage of human development. RUSSIAN JOURNAL OF GENETICS.
  5. Ferguson, LR. Nutrigenomics – Integrating genomic approaches into nutrition research. MOLECULAR DIAGNOSIS & THERAPY.
  6. Soloway, PD. Gene nutrient interactions and evolution. NUTRITION REVIEWS.
  7. Eichholzer, M.. Folic acid: a public-health challenge. LANCET.
  8. Houghton, LA. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. AMERICAN JOURNAL OF CLINICAL NUTRITION.
  9. Ejarque, I. A bioinformatic approach to epigenetic susceptibility in non-disjunctional diseases. BIOLOGICAL AND MEDICAL DATA ANALYSIS, PROCEEDINGS.
  10. Sweeney, MR. Evidence of unmetabolised folic acid in cord blood of newborn and serum of 4-day-old infants. BRITISH JOURNAL OF NUTRITION.
  11. Lucock, MD. The antifolate activity of tea catechins. CANCER RESEARCH.
  12. Kelemen, LE. Multivitamin and alcohol intake and folate receptor alpha expression in ovarian cancer. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION.
  13. Allegrucci, C. Human embryonic stem cells as a model for nutritional programming: An evaluation. REPRODUCTIVE TOXICOLOGY.

Supersize me and the fake food hypothesis

Is there any sense of genetic studies aiming at an association with body mass index? Will there ever be a public health strategy or any medical intervention based on a genetic marker?
I am recalling what Christoph – a friend of mine at medical school and a now professor for child psychiatry – once told me when he was working on his thesis about anorexia: “You only need to weight them for a diagnosis”. As there are now lots of weighing machines out there, there are plenty of DNAs (intended for different outcomes!), which might be a reason of the 5946 “obesity and gene” papers.
Will this help anybody? I fear, that responsibility is even shifted to “poor genes” (of course I acknowledge that there might be gene nutrient interactions – Paul Soloway wrote a nice essay on that). My view – developed with my wife over many years – is that that the obesity epidemics is largely an environmental trait of poor eating habits, wrong orientation on dress models and not enough physical activity. I recall also Professor Walter Willett – who has been my former advisor in Nutritional Epidemiology – that things can be quite simple. Check for his “Low Glycemic Index” on the web, find a sports club for biking, jogging or walking, concentrate on eating and use small spoons and forget about diets.
There is long-standing discussion, how the body signals by “being hungry” that something is missing (sorry, only 1 historic reference). Of course this works also in non-humans: Have you ever seen supersized animals? My guess is, that the well developed and unconscious food recognition process is largely fooled by pre-processed food that contains additives changing appearance, taste and smelling. So, you have now heard the first time about the fake food hypothesis. I do not believe so much in voluntarily overeating – it seems much more an involuntary repeated intake to find someting useful.
Coming back to our start: Imagine that
drugs that can block hunger (as we now learned the search for required food ingredients) and imagin that the developed world continues to eat their currently preferred food: Everybody will then need a professional nutrionists to balances his/her daily intake. So, we better save tax payer money for these BMI-gene studies. Yea, yea.

A hitch in the glitch of the switch

The CD14 / allergy story never ends – after many years and numerous contradictory reports. A new comment in the AJRCCM concludes that “further research is required” – at this time “research into the area of gene-by-environment interaction where large-scale studies, advanced assessment of environmental exposure of and experimental investigations of interactions are needed”. Is there any sense with neverending loops (except playground for hamster)? Nay, nay.

How deep is deep enough?

In case that the common disease / common variant is leading to nirvana, we urgently need to resequence common genes in large populations. 2kb long CRP is a particular good candidate which might be a reason why Crawford from Uwash resequenced ~500 individuals. They found indeed potentially relevant codings SNPs – of course rare (<1%) but they are there! There is a greater number in African-Americans than other populations and more than half are private to a single population (BTW more than half in dbSNP can not be validated). Of course tag SNPs would not discover them. Yea, yea.

Where we recombine

Finally, and long awaited, there is a first detailed analysis of mutational hotspots in the human genome by Myers from the McVean group in Oxford. There are roughly 1k-2k hotspots per chromosome, each 1kb-2kb long while there are no 200 kb without apparent recombination. Recombination avoids repeats, exons and L1 elements but likes GC as well as the THE1A/B 7mer CCT.CCC.T and the 8mer CCA.CGT.GG. As rec laways needs double strand breaks, are these also the first cancer motifs found? Yea, yea.

Again paranormal inheritance?

Following the exciting Lolle paper, now again non-chromosomal transfer of genetic information in a new study of Mary Alleman. Yes, of course, humans inherit mito DNa, there is imprinting, but also siRNA (not found in maize) or RNA polymerases (found!)? BTW much fuss of maternal imprinting in genetic epidemiology is simply preferential maternal reporting.


Pollen contamination may have been the reason for the Lolle/Pruitt results.