Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ 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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Antibodies recognizing specific Mycobacterium avium subsp. paratuberculosis's MAP3738c protein in type 1 diabetes mellitus children are associated with serum Th1 (CXCL10) chemokine

Recently Mycobacterium avium subsp. paratuberculosis (Map) was associated to type 1 diabetes mellitus (T1DM). In this study we investigated for Map presence in children affected by T1DM compared to healthy children. A pool of 212 sera from T1DM children at onset was compared to sera from 57 healthy children for humoral immune response towards the Map specific protein MAP3738c by ELISA. Serum concentrations of CXCL10 (pro-Th1) and CCL2 (pro-Th2) chemokines were also measured in both sera pool. Results showed that T1DM children had a stronger seropositivity towards MAP3738c protein compared to healthy children. Data highlighted also the correlation between serum activity of T1DM patients towards the specific protein of Map and the increase of CXCL10 concentration if compared to non-diabetic subjects. In conclusion, an immune response to Map in T1DM patients at onset was observed and this may indicate a role of the bacterium in triggering or precipitating the disease