Genetic determinants of hair, eye and skin pigmentation in Europeans

Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.     

Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.     

Functional epistasis on a common MHC haplotype associated with multiple sclerosis

Genes in the major histocompatibility complex (MHC) encode proteins important in activating antigen-specific immune responses. Alleles at adjacent MHC loci are often in strong linkage disequilibrium; however, little is known about the mechanisms responsible for this linkage disequilibrium. Here we report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles at separate loci by a functional assay in humanized mice indicates that the linkage disequilibrium between the two alleles may be due to a functional epistatic interaction, whereby one allele modifies the T-cell response activated by the second allele through activation-induced cell death. This functional epistasis is associated with a milder form of multiple-sclerosis-like disease. Such epistatic interaction might prove to be an important general mechanism for modifying exuberant immune responses that are deleterious to the host and could also help to explain the strong linkage disequilibrium in this and perhaps other HLA haplotypes.     

Herbaceous succession after burning of cut western juniper trees

The expansion of western juniper ( Juniperus occidentalis spp. occidentalis Hook.) in the northern Great Basin has resulted in the wide-scale conversion of sagebrush-steppe communities to juniper woodlands. Prescribed fire and mechanical cutting are the 2 main methods used to remove juniper and restore sagebrush steppe. Mechanical treatments commonly leave cut juniper on site. Disadvantages of leaving cut juniper are the increased fuel hazard and the potential for increased establishment and growth of invasive species. This study evaluated the response of herbaceous plants to winter burning of cut western juniper. Vegetation response was compared among 2 burning treatments (burning trees the first winter after cutting and burning the second winter after cutting), a control (cut-unburned juniper), and the interspace between cut trees. To minimize fire impacts to herbaceous perennials, cut trees were burned in the winter when soils and ground litter were frozen and/or soils were at field capacity. Only felled trees were burned, as fire did not carry into interspaces or litter mats around western juniper stumps. We hypothesized that winter season burning would increase herbaceous perennials and would reduce cheatgrass establishment when compared to the cut-unburned control. After 10 years, total herbaceous and perennial grass cover was 1.5- to 2-fold greater, respectively, in burned treatments compared to cut-unburned controls. Perennial grass density was 60% greater in the burned treatments than in the cut-unburned treatment and the interspace. Cheatgrass cover was twice as great in the control than in the 2 burn treatments and the interspace. We concluded that burning cut western juniper when soils were wet and frozen in winter enhanced community recovery of native perennials compared to leaving cut juniper unburned.     

Pharmacology: uncoupling the agony from ecstasy

The recreational use of amphetamine-type stimulants can produce a marked and sometimes lethal increase in body temperature. Here we show that mice deficient in a mitochondrial protein known as UCP-3 (for 'uncoupling protein-3') have a diminished thermogenic response to the drug MDMA (3,4-methylenedioxymethamphetamine, nicknamed 'ecstasy') and so are protected against this dangerously toxic effect. Our findings indicate that UCP-3 is important in MDMA-induced hyperthermia and point to a new therapeutic direction for solving an increasing public-health problem.     

Food for thought?: the relations between the Royal Society Food Committee and government, 1915-19

This paper traces the relationship between the food committees of the Royal Society and government during the First World War, concentrating on the period up to the resignation of Lord Devonport as first Food Controller. It argues that, in the context of a radical public science discourse emanating from some sections of the scientific community and greatly increased contacts between scientists and the government, the food scientists of the committees were moved to press for a formalization of the committees' role in food policy. The members constantly manoeuvered to achieve this aim, but also used a network of alternative channels into the heart of the policy process to get their findings translated into hard policy. In doing so, they explicitly rehearsed characteristic 'public science' arguments. In the institutional blur of wartime state-science relations, scientists often got close to the policy-making process. Post-War, the state swiftly moved to clarify the position: science was to be given more money, but was to be specifically blocked by new administrative arrangements embodied in the Haldane Report on the Machinery of Government from having any say in the core areas of general policy, the expert domain of the generalist policy-maker.