Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.</p

HPI appraisal of concentrations of heavy metals in dynamic and static flow of Ganga River System

Ganga River system is a life support system to sustain the people of northeast region, India, by providing freshwater resource. In this study, the seasonal heavy metal concentrations of Ganga River system at Haridwar region (India) have been characterised for metal pollution. The collection of water samples was done from 10 different locations and analysed for various metal parameters (Zn, Pb, Mn, Fe, Cu, Si, Al, Ni, Cd, Mg and Co) using a standard laboratory procedures. The pollution level was assessed from the observed concentrations by using Heavy Metal Pollution Index (HPI) for nine heavy metals. The observed values of HPI were found lower than the Critical Pollution Index value of 100 (average value 78.62 and 81.18) during the study period. The concentration of Fe and Mg is exceeding the desirable limits of the World Health Organization, Bureau of Indian Standards and US Environmental Protection Agency in all water samples throughout the study period. The levels of all the metals were higher in the monsoon season and lower in the winter season. The Karl Pearson’s correlation matrix was developed by using the mean values of all parameters and showed the light intensity positively correlated with biochemical oxygen demand (BOD) and sulphate which indicate good microbial activity. Dissolved oxygen and BOD is found negatively correlated. From this study, it is easy to understand the various harmful effects of metal pollution to irrigation water and health of local people

Analysis of interactions among the barriers to JIT production: interpretive structural modelling approach

Survival of the fittest' is the reality in modern global competition. Organizations around the globe are adopting or willing to embrace just-in-time (JIT) production to reinforce the competitiveness. Even though JIT is the most powerful inventory management methodologies it is not free from barriers. Barriers derail the implementation of JIT production system. One of the most significant tasks of top management is to identify and understand the relationship between the barriers to JIT production for alleviating its bad effects. The aims of this paper are to study the barriers hampering the implementation of successful JIT production and analysing the interactions among the barriers using interpretive structural modelling technique. Twelve barriers have been identified after reviewing literature. This paper offers a roadmap for preparing an action plan to tackle the barriers in successful implementation of JIT production

A draft map of the human proteome

The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease. © 2014 Macmillan Publishers Limited

Publisher Correction:Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article