The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

https://cdr.lib.unc.edu/downloads/v692t8920

A global reference for human genetic variation.

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.

Coming of age: ten years of next-generation sequencing technologies

An emerging body of multidisciplinary literature has documented the beneficial influence of physical activity engendered through aerobic exercise on selective aspects of brain function. Human and non-human animal studies have shown that aerobic exercise can improve a number of aspects of cognition and performance. Lack of physical activity, particularly among children in the developed world, is one of the major causes of obesity. Exercise might not only help to improve their physical health, but might also improve their academic performance. This article examines the positive effects of aerobic physical activity on cognition and brain function, at the molecular, cellular, systems and behavioural levels. A growing number of studies support the idea that physical exercise is a lifestyle factor that might lead to increased physical and mental health throughout life.

Be smart, exercise your heart: exercise effects on brain and cognition

Phenotypic characterisation of ring chromosome 22

Evidence of association between DRD4 and ADHD with conduct disturbance

Introduction: Case reports and uncontrolled studies of small case
series have suggested that abnormalities of chromosome 15 that
involve the Prader-Willi/Angelman Syndrome critical region (PWACR)
are associated with an increased risk for autism spectrum disorders.
We have investigated this issue in a large number of individuals with
various forms of chromosome 15 abnormality, comparing the frequency
of autistic symptomatology in these cases with the frequency in various
control samples.
Methods: Individuals with duplications (n¼30), supernumery
marker chromosome 15’s (n¼32), Prader-Willi Syndrome (disomy
cases¼49 deletion cases¼47) were assessed using questionnaire
(SCQ), innterview (ADI-R) and observational (ADOS-G) measures
of autistic symptomatology and the frequency of symptoms
compared to the that found in unaffected relative and Down syndrome
controls.
Results: Autisitc symptomatalogy was strongly associated with the
presence and number of extra copies of the PWACR. Within and
between group contrasts suggested that the increased risk for autistic
symptomatology was related to over expression of maternally
expressed genes.
Conclusions: Genes within the Prader-Willi/Angelman syndrome
critical region are candidate genes in the aetiology of autism spectrum
disorders. Dysregulation of maternally expressed genes is a potential
candidate mechanism. However, molecular genetic organisation in
this region is complex with methylation and chromatin structure
change and epistatic interactions with genes in other regions being
possible.

Sarah Curran

Papers

Phenotypic characterisation of ring chromosome 22

Evidence of association between DRD4 and ADHD with conduct disturbance

Chromosome 15 abnormalities and autistic symptomatology: case—control investigations