Allotransplantation of rat parathyroid glands: effects of organ culture and transplantation into the adrenal gland.

Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB2) to Fischer rats (AgB1) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.     

Measurement of urinary steroid production rates using stable-isotopes and GC-MS.

The urinary production rate of pregnenolone has been determined for a male subject using 7,7-d2-pregnenolone as an isotopic tracer.     

Human behaviour: Egalitarian motive and altruistic punishment

Altruistic punishment is a behaviour in which individuals punish others at a cost to themselves in order to provide a public good. Fehr and G?chter present experimental evidence in humans indicating that negative emotions towards non-cooperators motivate punishment, which, in turn, provokes a high degree of cooperation. Using Fehr and G?chter's original data, we provide an alternative analysis of their experiment that suggests that egalitarian motives are more important than motives for punishing non-cooperative behaviour. This finding is consistent with evidence that humans may have an evolutionary incentive to punish the highest earners in order to promote equality, rather than cooperation.     

A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk

The identification of common variants that contribute to the genesis of human inherited disorders remains a significant challenge. Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes. We have used family-based association studies to identify a disease interval, and integrated this with comparative and functional genomic analysis to prioritize conserved and functional elements within which mutations can be sought. We now show that a common non-coding RET variant within a conserved enhancer-like sequence in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribution to risk than rare alleles do. This mutation reduces in vitro enhancer activity markedly, has low penetrance, has different genetic effects in males and females, and explains several features of the complex inheritance pattern of HSCR. Thus, common low-penetrance variants, identified by association studies, can underlie both common and rare diseases.     

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.     

Genome sequence of the Brown Norway rat yields insights into mammalian evolution

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.