Maize HapMap2 identifies extant variation from a genome in flux

Whereas breeders have exploited diversity in maize for yield improvements, there has been limited progress in using beneficial alleles in undomesticated varieties. Characterizing standing variation in this complex genome has been challenging, with only a small fraction of it described to date. Using a population genetics scoring model, we identified 55 million SNPs in 103 lines across pre-domestication and domesticated Zea mays varieties, including a representative from the sister genus Tripsacum. We find that structural variations are pervasive in the Z. mays genome and are enriched at loci associated with important traits. By investigating the drivers of genome size variation, we find that the larger Tripsacum genome can be explained by transposable element abundance rather than an allopolyploid origin. In contrast, intraspecies genome size variation seems to be controlled by chromosomal knob content. There is tremendous overlap in key gene content in maize and Tripsacum, suggesting that adaptations from Tripsacum (for example, perennialism and frost and drought tolerance) can likely be integrated into maize.     

Male-pattern baldness susceptibility locus at 20p11

We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)).     

Signal requirements in the step-wise functional maturation of cytotoxic T lymphocytes

The generation of effector cytotoxic T lymphocytes from resting precursors proceeds through a series of steps in a pathway that, in aggregate, involves both proliferation and development of cytotoxicity. To understand the relationship of the various signals (mitogens and/or lymphokines) that bring about progress along this pathway, it is desirable to define a series of 'minimal signals', each of which stimulates the cell to proceed to a further stage in this process of differentiation. Stimulation of lymphocytes with two different monoclonal antibodies directed against the CD2 surface molecule induces a proliferative response; we report here that both CD4+ and CD8+ cells proliferate in response to such a stimulus but do not develop cytotoxicity. Addition of recombinant gamma-interferon (rIFN-gamma) or recombinant IL-2 (rIL-2) to the activated cells leads to acquisition of cytotoxic status by the CD8+ cells but not the CD4+ cells. The availability, in addition to precursors and effectors, of an apparently intermediate stage in the form of proliferating CD8+ cells that are non-cytotoxic should facilitate both cellular and molecular studies of this maturation pathway; the differences between CD4+ and CD8+ cells in development of cytotoxicity under these experimental conditions is a valuable model for understanding differentiation of T lymphocytes.     

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.     

Surprising dissimilarities in a newly formed pair of 'identical twin' stars

The mass and chemical composition of a star are the primary determinants of its basic physical properties-radius, temperature and luminosity-and how those properties evolve with time. Accordingly, two stars born at the same time, from the same natal material and with the same mass, are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 per cent. Here we report that these twin stars have surface temperatures differing by approximately 300 K ( approximately 10 per cent) and luminosities differing by approximately 50 per cent, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10 per cent. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system. Our findings reveal cosmic limits on the age synchronization of young binary stars, often used as tests for the age calibrations of star-formation models.     

A mass transfer origin for blue stragglers in NGC 188 as revealed by half-solar-mass companions

In open star clusters, where all members formed at about the same time, blue straggler stars are typically observed to be brighter and bluer than hydrogen-burning main-sequence stars, and therefore should already have evolved into giant stars and stellar remnants. Correlations between blue straggler frequency and cluster binary star fraction, core mass and radial position suggest that mass transfer or mergers in binary stars dominates the production of blue stragglers in open clusters. Analytic models, detailed observations and sophisticated N-body simulations, however, argue in favour of stellar collisions. Here we report that the blue stragglers in long-period binaries in the old (7?×?10(9)-year) open cluster NGC 188 have companions with masses of about half a solar mass, with a surprisingly narrow mass distribution. This conclusively rules out a collisional origin, as the collision hypothesis predicts a companion mass distribution with significantly higher masses. Mergers in hierarchical triple stars are marginally permitted by the data, but the observations do not favour this hypothesis. The data are highly consistent with a mass transfer origin for the long-period blue straggler binaries in NGC 188, in which the companions would be white dwarfs of about half a solar mass.     

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.     

上海市百岁老人的谱系及其分析

本文调查了上海市百岁老人的性别、职业和谱系,并绘制了57个完整的寿命谱系图,其中男性10名(占总数的17.5%),女性47名(占82.5%).男性中脑力劳动者4名(占男性总数的40%),体力劳动者6名(占60%);女性中脑力劳动者1人(占女性总数的2.1%),体力劳动者3人(占6.4%),操持家务者43人(占91.5%).有长寿家族史者40人(占寿命家族史清楚者的70.2%),无长寿家族史者17人(占29.8%).百岁老人配偶寿长≥70岁者,其已故子女的平均寿命高于配偶<70岁的.作者认为长寿是遗传的,并着重从遗传和环境两方面分析了女寿星数明显多于男寿星数的原因.