Highly effective SNP-based association mapping and management of recessive defects in livestock

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.     

Geochemical tracing of Pacific-to-Atlantic upper-mantle flow through the Drake passage

The Earth's convecting upper mantle can be viewed as comprising three main reservoirs, beneath the Pacific, Atlantic and Indian oceans. Because of the uneven global distribution and migration of ridges and subduction zones, the surface area of the Pacific reservoir is at present contracting at about 0.6 km2 x y(r-1), while the Atlantic and Indian reservoirs are growing at about 0.45 km2 x yr(-1) and 0.15 km2 x yr(-1), respectively. Garfunkel and others have argued that there must accordingly be net mantle flow from the Pacific to the Atlantic and Indian reservoirs (in order to maintain mass balance), and Alvarez further predicted that this flow should be restricted to the few parts of the Pacific rim (here termed 'gateways') where there are no continental roots or subduction zones that might act as barriers to shallow mantle flow. The main Pacific gateways are, according to Alvarez, the southeast Indian Ocean, the Caribbean Sea and the Drake passage. Here we report geochemical data which confirm that there has been some outflow of Pacific mantle into the Drake passage--but probably in response to regional tectonic constraints, rather than global mass-balance requirements. We also show that a mantle domain boundary, equivalent to the Australian-Antarctic discordance, must lie between the Drake passage and the east Scotia Sea.     

The sizes and characteristics of the minority ethnic populations of Great Britain--latest estimates

This article presents estimates of the minority ethnic populations of Great Britain in 2000 and describes the regional distributions of the different groups. It also discusses changes in the sizes of the different minority ethnic populations during the 1990s. The paper provides information on some key demographic features of these populations at the end of the 1990s--age and sex structures, proportions born in the United Kingdom and whether children lived with their natural parents.     

The demographic situation in the European Union

This article draws selected material from the annual Yearbook on Demography (2000 edition) published by Eurostat, the Statistical Office of the European Communities. Some key comparisons with other regions of the world are included, together with a broad picture of the demographic situation in the European Union. Topic coverage is selective.     

On the mechanism of immunosympathectomy

Summary The effects in vivo and in vitro of the antiserum to mouse nerve growth factor (NGF) are independent of the presence of complement. These results are consistent with the view that the antiserum acts by neutralizing endogenous NGF.Acknowledgments. Financial support from the Whitehall Foundation, New York, The Wellcome Foundation, U.K. (to J.R.C.) and the Science Research Council (Studentship to M.E.) is gratefully acknowledged. We thank Professor J.H. Humphrey, National Institute for Medical, Research, Mill Hill, London, for discussion and determination of plasma C3 levels.     

Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function

Neuronal ceroid lipofuscinoses (NCL) are caused by mutations in eight different genes, are characterized by lysosomal accumulation of autofluorescent storage material, and result in a disease that causes degeneration of the central nervous system (CNS). Although functions are defined for some of the soluble proteins that are defective in NCL (cathepsin D, PPT1, and TPP1), the primary function of the other proteins defective in NCLs (CLN3, CLN5, CLN6, CLN7, and CLN8) remain poorly defined. Understanding the localization and network of interactions for these proteins can offer clues as to the function of the NCL proteins and also the pathways that will be disrupted in their absence. Here, we present a review of the current understanding of the localization, interactions, and function of the proteins associated with NCL.     

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.