Genetic approaches to studying complex human disease

Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using both established and novel genomic technologies, including candidate gene resequencing, high-throughput targeted microarray genotyping and candidate variant genotyping. We demonstrate that a private and common variant, p.G116S, within the low-density lipoprotein receptor (LDLR) gene among Inuit descendants has a large effect on plasma cholesterol; that variation in cardio-metabolic and Alzheimer disease (AD) loci is not associated with susceptibility to the pre-dementia phenotype known as “cognitive impairment, no dementia”; and that established type 2 diabetes (T2D) variants are not associated with T2D susceptibility among select aboriginal Canadian and Greenland cohorts. Together, these studies represent a selection of established and novel genomic strategies for the investigation of complex disease genetics which are likely to remain fundamental in the continued investigation of complex disease pathogenesis

Genetic analysis of somatic cell score and udder type traits in South African Holstein cows

Selection accuracy for resistance to mastitis may be increased by combining somatic cell score (SCS) and udder type into an udder health index, using genetic parameter estimates among them. A multi-trait animal model was used to estimate genetic parameters among lactation average SCS and udder type traits in South African Holstein cattle, through REML procedures. Data comprised records on 22 999 Holstein cows in 722 herds, collected through the National Milk Recording Scheme from 1996 to 2002. Average SCS in the first three lactations (SCS1, SCS2, SCS3) were considered as different traits and the udder type traits were fore udder attachment (FUA), rear udder height (RUH), udder cleft (UC), udder depth (UD), fore teat length (FTL) and fore teat placement (FTP). Heritability estimates for SCS were 0.19 ± 0.02, 0.17 ± 0.02 and 0.19 ± 0.02, respectively for SCS1, SCS2 and SCS3. Udder type traits had heritability estimates ranging from 0.13 ± 0.01 for UC to 0.34 ± 0.01 for FTL. The genetic correlations between lactation SCS ranged from 0.82 ± 0.04 to 0.99 ± 0.03 for correlations of SCS3 with SCS1 and SCS2, respectively. Genetic correlations between SCS and udder type traits were in the range -0.01 ± 0.07 between FUA and SCS3 to -0.38 ± 0.04 between UD and SCS1 and SCS2. Slow genetic progress is expected when selection is applied independently on SCS and udder type traits, due to the generally low heritability estimates. Low, shallow udders with narrowly placed teats are associated with low SCS in the South African Holstein population. Keywords: Genetic parameters, mastitis, selection accuracy, udder healthSouth African Journal of Animal Science Vol. 38 (1) 2008: pp. 1-1

Rock Mass Behaviour Assessment for Large Cavern in Rock

A large power house cavern (22m x 50m x 250m) is proposed to be excavated for installing a 1000 MW hydroelectric power plant for Tehri Dam Project. The gorge chosen for the dam is very narrow and the topography is rugged and inhospitable. This dampened the process of preconstruction investigations. A number of tunnels were constructed for various project structures in the vicinity of the cavern. This provided an excellent opportunity to study the rock mass behaviour. Tunnel closure and rock loads were monitored with the help of instruments. Deformation moduli were also determined for different rock grades with the help of various techniques. A voluminous data had been obtained. This data had been analyzed thoroughly and values of various parameters had been suggested for the final design of underground cavern and the supporting structures

Pseudomonas septicaemia: in a case of pancytopenia

Pseudomonal infection is a rare condition with multiple systemic complications. A new condition of interest is ecthyma gangrenosum in a patient with pseudomonas septicaemia with pancytopenia and megaloblastic anaemia. So here we present you the case of Ecthyma gangrenosum in a 20-year-old female with pseudomonas septicaemia due to pancytopenia. A high degree of clinical suspicion is required, but a tissue sample is ultimately necessary for definitive diagnosis