Friday, October 21, 2011

Antagonistic pleiotropy - the case for BRCA mutations

In a natural fertility population, these authors find that carriers of BRCA mutations have more children, shorter birth intervals, a later end to child-bearing, and "excess post-reproductive mortality risks".

Effects of BRCA1 and BRCA2 mutations on female fertility
Ken R. Smith, Heidi A. Hanson, Geraldine P. Mineau, and Saundra S. Buys
Proc. R. Soc. B
Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.

Thursday, October 20, 2011

Taino and African ancestry in Puerto Ricans

Here's a news story about a talk given at the latest ASHG/ICHG meeting. Bustamante et al. have been looking at admixture among Puerto Ricans (apparently the latest addition to the 1000 Genomes project), and specifically looking at the lengths of DNA segments belonging to different groups in order to infer the temporal and geographic patterns of historical admixture.
Rebuilding the genome of a hidden ethnicity

Thursday, June 16, 2011

Persistence hunting - is it really possible?

Here's an interesting post from John Hawks' blog about a magazine article about running, evolution (and hunting?) enthusiasts who try to see how hard it would be to track a pronghorn in New Mexico.
Apparently they failed. I'm still not convinced that this really debunks the theory that this type of hunting is possible or was important in our evolutionary history, but pretty cool to see people trying it...sounds like fun!

Tuesday, February 22, 2011

Scientists like to "fondle their problems"

I thought this was a funny quote from an interesting article in Nature discussing the fact, that despite the identification of many disease-relevant proteins, "75% of protein research still focuses on the 10% of proteins that were known before the genome was mapped".

This is actually probably mostly driven by the conservative nature of funding sources.
From the authors:
Granting systems must be more daring, institutions must foster and reward risk, and the entire biomedical community must play down the legacy of the literature and let new evidence guide research. Genome-wide tools such as the DNA microarrays used in association studies have allowed geneticists to ignore preconceived ideas about disease mechanisms and pursue a remarkably successful broad-brush approach; this approach should be embraced more generally.

Too many roads not taken
Aled M. Edwards, Ruth Isserlin, Gary D. Bader, Stephen V. Frye, Timothy M. Willson & Frank H. Yu
Nature Volume: 470, Pages:163–165

Sunday, February 20, 2011

Wolpoff interviewed by Razib

Here's a very interesting video of a discussion between Razib Khan and Milford Wolpoff.
They cover a pretty wide range of topics, but mostly centered on the multiregional model of human evolution, with some discussion about the "sociology of science" weaved in throughout.

Thursday, January 27, 2011

Jared Diamond on type-2 diabetes in India

The latest issue of Nature has a piece by Jared Diamond about the diabetes epidemic in India, and how some aspects of its pathology are unique among Indians as compared to other groups.
Medicine: Diabetes in India
Jared Diamond
Nature Volume: 469, Pages:478–479 : 27 January 2011

Some of the more interesting points:
In 2010, the average age-adjusted prevalence of diabetes in India was 8%, higher than that in most European countries
In India, as in the West, diabetes is ultimately due to chronically high levels of blood glucose, and some of the clinical consequences are similar. But whereas Westerners think of type 2 diabetes as an adult-onset disease appearing especially after the age of 50, Indians (and Chinese, Japanese and Aboriginal Australians) with diabetes exhibit symptoms at an age one or two decades younger than that. The age of onset in India has been shifting towards ever-younger people even within the past decade9 — among Indians in their late teens, 'adult-onset' diabetes already manifests itself more often than does 'juvenile-onset' diabetes. In Britain, the prevalence of type 2 diabetes is 14 times higher in Asian than European children. And although obesity is a risk factor for diabetes both in India and in the West, the disease appears at a lower threshold of obesity in India, as is also the case in China, Japan and other Asian countries.

Symptoms also differ between Indians and Westerners: Indians with diabetes are less likely to develop blindness and kidney disease, but much more likely to suffer coronary artery disease at a relatively young age
He stresses the difference in prevalence between rich and poor Indians, and discusses how these differences are the opposite of what we observe in the US and Europe, for example, where socio-economic status is positively correlated with health.
Given Jared Diamond's past speculation on the evolutionary and/or genetic causes of these types of epidemics, I thought he might have expounded on that, as others have, but alas, he didn't.

Thursday, January 20, 2011

Selection can increase genetic diversity - the example of Somali camel herders

The interesting finding here is that diversity in the LCT/MCM6 region is increased rather than reduced among those who are lactose tolerant compared to those who are lactose intolerant. Unlike in Europe where a single mutation swept through much of the population, among this East African population, there are several mutations that arose on different haplotype backgrounds that have a similar phenotypic effect. The result is that genetic diversity in this genomic region is increased. The authors have a pretty good discussion about the possible reasons for the patterns they observe.
These types of examples, albeit simplistic compared to other traits, are great for our basic understanding of the genetic basis of complex traits, and for our understanding of the genetic avenues leading to adaptation.

Multiple rare variants as a cause of a common phenotype: several different lactase persistence associated alleles in a single ethnic group.
Ingram CJ, Raga TO, Tarekegn A, Browning SL, Elamin MF, Bekele E, Thomas MG, Weale ME, Bradman N, Swallow DM.
J Mol Evol. 2009 Dec;69(6):579-88.
Abstract:Persistence of intestinal lactase into adulthood allows humans to use milk from other mammals as a source of food and water. This genetic trait has arisen by convergent evolution and the derived alleles of at least three different single nucleotide polymorphisms (-13910C>T, -13915T>G, -14010G>C) are associated with lactase persistence in different populations. Each allele occurs on an extended haplotype, consistent with positive directional selection. The SNPs are located in an 'enhancer' sequence in an intron of a neighboring gene (MCM6) and modulate lactase transcription in vitro. However, a number of lactase persistent individuals carry none of these alleles, but other low-frequency single nucleotide polymorphisms have been observed in the same region. Here we examine a cohort of 107 milk-drinking Somali camel-herders from Ethiopia. Eight polymorphic sites are identified in the enhancer. -13915*G and -13907*G (a previously reported candidate) are each significantly associated with lactase persistence. A new allele, -14009*G, has borderline association with lactase persistence, but loses significance after correction for multiple testing. Sequence diversity of the enhancer is significantly higher in the lactase persistent members of this and a second cohort compared with non-persistent members of the two groups (P = 7.7 x 10(-9) and 1.0 x 10(-3)). By comparing other loci, we show that this difference is not due to population sub-structure, demonstrating that increased diversity can accompany selection. This contrasts with the well-documented observation that positive selection decreases diversity by driving up the frequency of a single advantageous allele, and has implications for association studies.
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