MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis

The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.     

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.     

Mutations in dynamin 2 cause dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.     

The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone

We identified the gene underlying Marinesco-Sj?gren syndrome, which is characterized by cerebellar ataxia, progressive myopathy and cataracts. We identified four disease-associated, predicted loss-of-function mutations in SIL1, which encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5. These data, together with the similar spatial and temporal patterns of tissue expression of Sil1 and Hspa5, suggest that disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sj?gren syndrome.     

Paramagnetism of human serum proteins demonstrated by two-stage electromagnetophoresis

Zusammenfassung Normale Serumproteine wurden mittels zweistufiger Elektromagnetophorese in Polyacrylamidgel, einer neuen Technik, aufgetrennt, wobei die Trennung auf Grund der paramagnetischen Eigenschaften der einzelnen Proteine erfolgt.

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Supported by William Beaumont Hospital Research Institute in Affiliation with the Research Laboratories, General Motors Corporation and Department of Pathology, School of Medicine, Wayne State University.     

Induction of developmental anomalies in mice by maternal stress

Summary The short-time restraint of pregnant mice on day 8 of gestation led to a significant increase of the anomaly rate in fetuses. This effect may be due to stress factors of endocrine origin.The technical assistance of Mrs E. Frei is gratefully acknowledged. Supported by the Swiss National Foundation for Scientific Research.     

Influence of age on the plasma hormonal iodine response to thyrotropin injection in young calves]

The influence of age upon the increase in plasma hormonal iodine level following an intravenous injection of bovine TSH (0.2 USP units/kg) was studied in young jersey calves. The response to TSH increased between birth and the 7th day, then decreased regularly until the end of the third month. Reasons for these variations are discussed according to some results obtained following TSH injections.     

Chronic split brain stem preparation: Effect on the sleep-waking cycle

Résumé La préparation du chat à tronc cérébral dédoublé peut être conservée pendant plusieurs mois en bon état. Elle se caractérise par un très haut niveau de vigilance avec réduction du sommeil lent et du sommeil rapide. Lorsque la section sagitale médiane est très étendue, alternativement chaque hemisphère peut présenter un tracé lent tandis que l'autre hemisphère présente un tracé rapide; cette asynchronie peut durer jusqu'à 25 min.

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A preliminary paper has been presented at Ass. for Psychophysiological Study of Sleep, Gainesville, Florida, March, 1966.