Genome partitioning of genetic variation for complex traits using common SNPs

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ～45%, ～17%, ～25% and ～21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ～0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.     

Discovery of the Missing Correspondence between Carl Friedrich Gauss and the Rev. Nevil Maskelyne (1802–5)

More than 30 years ago in Annals of Science, Dr. Eric Forbes of the University of Edinburgh published the correspondence between Carl Gauss and Great Britain's Astronomer Royal, Nevil Maskelyne. Five of the letters he listed as missing have now been discovered, along with two entirely new letters he was unaware of. Their nearly complete correspondence can now be read for the first time in 200 years.     

Estimation of genetic trend in racing performance of thoroughbred horses

Thoroughbred horses have been bred exclusively for racing in England since Tudor times and thoroughbred horse racing is now practised in over 40 countries and involves more than half-a-million horses worldwide. The genetic origins of the thoroughbred go back largely to horses imported from the Middle East and North Africa to England in the late seventeenth and early eighteenth centuries. Since the establishment of the Stud Book in 1791, the population has been effectively closed to outside sources, and over 80% of the thoroughbred population's gene pool derives from 31 known ancestors from this early period. Despite intense directional selection, especially on the male side, and the generally high heritabilities of various measures of racing performance, winning times of classic races have not improved in recent decades. One possible explanation for this is that additive genetic variance in performance may have been exhausted in the face of strong selection. To test this, we have estimated the genetic trend in performance over the period 1952-77 using TIMEFORM handicap ratings which are based entirely on the horse's own performance, and express its racing merit as a weight in pounds which the compilers believe the horse should carry in an average free-handicap race. These ratings take into account such factors as the firmness of the ground, the distance and the level of the competition. Our results indicate that the failure of winning times to improve is not due to insufficient genetic variance in the thoroughbred population as a whole.     

Synthesis of 5′-deoxypyridoxal derivatives

Summary A convenient synthesis of 5-deoxypyridoxal derivatives is described. The method involves catalytic hydrogenolysis of the corresponding 5-phosphorylated derivatives; products are obtained in high yields.Supported by PHS Grant No. 5429-16-9.     

Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor

Protease nexin-II (PN-II) is a protease inhibitor that forms SDS-resistant inhibitory complexes with the epidermal growth factor (EGF)-binding protein, the gamma-subunit of nerve growth factor, and trypsin. The properties of PN-II indicate that it has a role in the regulation of certain proteases in the extracellular environment. Here we describe more of the amino-acid sequence of PN-II and its identity to the deduced sequence of the amyloid beta-protein precursor (APP). Amyloid beta-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome. A monoclonal antibody against PN-II (designated mAbP2-1) recognized PN-II in immunoblots of serum-free culture medium from human glioblastoma cells and neuroblastoma cells, as well as in homogenates of normal and Alzheimer's disease brains. In addition, mAbP2-1 stained neuritic plaques in Alzheimer's disease brain. PN-II was a potent inhibitor of chymotrypsin with an inhibition constant Ki of 6 x 10(-10)M. Together, these data demonstrate that PN-II and APP are probably the same protein. The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolysis in the pathogenesis of Alzheimer's disease.     

Slowing of the Atlantic meridional overturning circulation at 25 degrees N

The Atlantic meridional overturning circulation carries warm upper waters into far-northern latitudes and returns cold deep waters southward across the Equator. Its heat transport makes a substantial contribution to the moderate climate of maritime and continental Europe, and any slowdown in the overturning circulation would have profound implications for climate change. A transatlantic section along latitude 25 degrees N has been used as a baseline for estimating the overturning circulation and associated heat transport. Here we analyse a new 25 degrees N transatlantic section and compare it with four previous sections taken over the past five decades. The comparison suggests that the Atlantic meridional overturning circulation has slowed by about 30 per cent between 1957 and 2004. Whereas the northward transport in the Gulf Stream across 25 degrees N has remained nearly constant, the slowing is evident both in a 50 per cent larger southward-moving mid-ocean recirculation of thermocline waters, and also in a 50 per cent decrease in the southward transport of lower North Atlantic Deep Water between 3,000 and 5,000 m in depth. In 2004, more of the northward Gulf Stream flow was recirculating back southward in the thermocline within the subtropical gyre, and less was returning southward at depth.