PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.     

Genetic clonal diversity predicts progression to esophageal adenocarcinoma

Neoplasms are thought to progress to cancer through genetic instability generating cellular diversity and clonal expansions driven by selection for mutations in cancer genes. Despite advances in the study of molecular biology of cancer genes, relatively little is known about evolutionary mechanisms that drive neoplastic progression. It is unknown, for example, which may be more predictive of future progression of a neoplasm: genetic homogenization of the neoplasm, possibly caused by a clonal expansion, or the accumulation of clonal diversity. Here, in a prospective study, we show that clonal diversity measures adapted from ecology and evolution can predict progression to adenocarcinoma in the premalignant condition known as Barrett's esophagus, even when controlling for established genetic risk factors, including lesions in TP53 (p53; ref. 6) and ploidy abnormalities. Progression to cancer through accumulation of clonal diversity, on which natural selection acts, may be a fundamental principle of neoplasia with important clinical implications.     

A road map for efficient and reliable human genome epidemiology

Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.     

Genome-wide association analysis identifies susceptibility loci for migraine without aura

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.     

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.     

A copy number variation morbidity map of developmental delay

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ～14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.     

Comments on Indivisibles and Infinitesimals: A Response to David Sherry,by Amir Alexander: In View of the Original Book

A set of six publications have introduced, commented, criticized and defended Amir Alexander’s book on infinitesimals published in 2014. The aim of the following article is to bring the various arguments together.     

采取综合配套措施提高飞播造林成效

飞播造林具有速度快、省劳力、投资小，在短时间内完成大面积造林任务的特点。经过对我市飞播造林调查结果分析后得出，在飞播中采用植被处理、粗放整地、树种混交播种、多效复合剂拌种包衣4项综合配套技术措施，可以减少鸟鼠危害，增加种子发芽，有效提高飞播造林成效面积。     

Comparison of distribution and habitat characteristics between an endemic and a wide-ranging cryptic species of Peromyscus on the Baja California Peninsula

Peromyscus eva and Peromyscus fraterculus are 2 morphologically similar species of the Peromyscus eremicus group occurring on the Baja California Peninsula. Due to the similarity between these 2 species, their ranges have been greatly confused; consequently, the specific habitat characteristics for each group are not well known. The goal of this study was to assess distribution ranges and characteristics of preferred habitats for P. eva and P. fraterculus in more detail. We identified taxonomy of individuals by evaluating genetic patterns produced by restriction fragment length polymorphisms (RFLPs). We evaluated the banding pattern generated by Alu I and Bam HI restriction enzymes in an 850-bp cytochrome b fragment. Consistent differences in number and size of fragments allowed for discrimination of individuals to species. The heterogeneity and evenness indexes showed that the microhabitat of P. fraterculus contained less-diverse soil types and is more homogeneous than the microhabitat of P. eva. In the state of Baja California Sur, P. eva occurs exclusively in the flat areas along the Pacific coast from the Vizcaino Desert to the south, including Margarita Island, with one small population in the Loreto area adjacent to Carmen Island. The habitats occupied by P. eva were heterogeneous (areas with friable, soft sandy soil and a low percentage of small stones). Peromyscus fraterculus occurs mostly in Baja California Norte, with some populations distributed in Baja California Sur, particularly in the western areas of the Vizcaino Desert along the mountain range, in the gulf side of the peninsula south of the city of La Paz, and in a small area on the eastern side of Sierra de Las Cruces. This species was mostly found on hard soil with high medium-size stone content.