Sunday, August 30, 2009

Got some performance enhancing polymorphisms?

First of all, gotta love the term "Performance Enhanding Polymorphisms" (PEPs). This is a review paper describing what we know about the genetics of athletic performance. They focus on ACE, ACTN3, MSTN, NOS3 and several other genes. In light of recent performances, and just out of curiosity, let's get some genotypes on these three people:
Usain Bolt
Lance Armstrong
Michael Phelps

Genetics of Athletic Performance
Elaine A. Ostrander, Heather J. Huson, and Gary K. Ostrander
Annual Review of Genomics and Human Genetics Vol. 10: 407-429
Abstract: Performance enhancing polymorphisms (PEPs) are examples of natural genetic variation that affect the outcome of athletic challenges. Elite athletes, and what separates them from the average competitor, have been the subjects of discussion and debate for decades. While training, diet, and mental fitness are all clearly important contributors to achieving athletic success, the fact that individuals reaching the pinnacle of their chosen sports often share both physical and physiological attributes suggests a role for genetics. That multiple members of a family often participate in highly competitive events, such as the Olympics, further supports this argument. In this review, we discuss what is known regarding the genes and gene families, including the mitochondrial genome, that are believed to play a role in human athletic performance. Where possible, we describe the physiological impact of the critical gene variants and consider predictions about other potentially important genes. Finally, we discuss the implications of these findings on the future for competitive athletics.

Friday, August 28, 2009

Geographical origin and dating of the lactase persistence allele

See Dienekes' blog post about a new paper that purports the origin of the lactase persistence allele to be somewhere in the Austria/Czech Republic area, around 7,500 years ago.
From the abstract:
Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D.

Saturday, August 22, 2009

A set of AIMs that can distinguish within continents

An ancestry informative marker set for determining continental origin: validation and extension using human genome diversity panels.
Nassir R, Kosoy R, Tian C, White PA, Butler LM, Silva G, Kittles R, Alarcon-Riquelme ME, Gregersen PK, Belmont JW, De La Vega FM, Seldin MF.
BMC Genet. 2009 Jul 24;10(1):39.
ABSTRACT: BACKGROUND: Case-control genetic studies of complex human diseases can be confounded by population stratification. This issue can be addressed using panels of ancestry informative markers (AIMs) that can provide substantial population substructure information. Previously, we described a panel of 128 SNP AIMs that were designed as a tool for ascertaining the origins of subjects from Europe, Sub-Saharan Africa, Americas, and East Asia. RESULTS: In this study, genotypes from Human Genome Diversity Panel populations were used to further evaluate a 93 SNP AIM panel, a subset of the 128 AIMS set, for distinguishing continental origins. Using both model-based and relatively model-independent methods, we here confirm the ability of this AIM set to distinguish diverse population groups that were not previously evaluated. This study included multiple population groups from Oceana, South Asia, East Asia, Sub-Saharan Africa, North and South America, and Europe. In addition, the 93 AIM set provides population substructure information that can, for example, distinguish Arab and Ashkenazi from Northern European population groups and Pygmy from other Sub-Saharan African population groups. CONCLUSION: These data provide additional support for using the 93 AIM set to efficiently identify continental subject groups for genetic studies, to identify study population outliers, and to control for admixture in association studies.

Tuesday, August 04, 2009

Epigenetics and disease causality

Obviously this has a lot of important implications, one of which is the fact that we may be overestimating the heritability of traits like obesity and diabetes.

Epigenetic Inheritance and the Missing Heritability Problem
Montgomery Slatkin
Genetics July 2009; 182: 845
Abstract: Epigenetic phenomena, and in particularly heritable epigenetic changes, or transgenerational effects, are the subject of much discussion in the current literature. This paper presents a model of transgenerational epigenetic inheritance and explores the effect of epigenetic inheritance on the risk and recurrence risk of a complex disease. The model assumes that epigenetic modifications of the genome are gained and lost at specified rates and that each modification contributes multiplicatively to disease risk. The potentially high rate of loss of epigenetic modifications causes the probability of identity in state in close relatives to be smaller than is implied by their relatedness. As a consequence, the recurrence risk to close relatives is reduced. Although epigenetic modifications may contribute substantially to average risk, they will not contribute much to recurrence risk and heritability unless they persist on average for many generations. If they do persist for long times, they are equivalent to mutations and hence are likely to be in linkage disequilibrium with SNPs surveyed in genome-wide association studies. Thus epigenetic modifications are a potential solution to the problem of missing causality of complex diseases but not to the problem of missing heritability. The model highlights the need for empirical estimates of the persistence times of heritable epialleles.
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