Icelandic Inland Wetlands: Characteristics and Extent of Draining

Iceland has inland wetland areas with soils exhibiting both Andosol and Histosol properties which are uncommon elsewhere on Earth. They are generally fertile, with higher bird-nest densities than in similar wetlands in the neighboring countries, with nutrients released by rapid weathering of aeolian materials of basaltic nature. Icelandic inland wetlands cover about 9000 km2 constituting 19.4 % of the vegetated surfaces of the island. The wetland soils are often 1–3 m thick and store 33 to >100 kg C m−2. They have been subjected to broad-scale subsidy-driven draining for agricultural purposes. About 47 % of Icelandic inland wetlands are impacted by drainage. The ditch network extends about 30,000 km, mainly in lowland areas, where about 70 % of the wetland areas are impacted. There are >1 million wetland patches, most of them <1 ha. Much of the wetlands impacted from drainage are not used for intensive agriculture such as haymaking, however some are used for grazing. There is a need to prioritize the protection of undrained wetlands and their restoration based on a broad range of factors.Peer Reviewe

POGZ Is Required for Silencing Mouse Embryonic β-like Hemoglobin and Human Fetal Hemoglobin Expression

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesFetal globin genes are transcriptionally silenced during embryogenesis through hemoglobin switching. Strategies to derepress fetal globin expression in the adult could alleviate symptoms in sickle cell disease and β-thalassemia. We identified a zinc-finger protein, pogo transposable element with zinc-finger domain (POGZ), expressed in hematopoietic progenitor cells. Targeted deletion of Pogz in adult hematopoietic cells in vivo results in persistence of embryonic β-like globin expression without affecting erythroid development. POGZ binds to the Bcl11a promoter and erythroid-specific intragenic regulatory regions. Pogz+/- mice show elevated embryonic β-like globin expression, suggesting that partial reduction of Pogz expression results in persistence of embryonic β-like globin expression. Knockdown of POGZ in primary human CD34+ progenitor cell-derived erythroblasts reduces BCL11A expression, a known repressor of embryonic β-like globin expression, and increases fetal hemoglobin expression. These findings are significant, since new therapeutic targets and strategies are needed to treat β-globin disorders.Frederick National Laboratory for Cancer Research, NIH intramural research program of the NHLBI, NIH intramural research program of the NIDDK, NIH USUH

Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPredicting the pathogenicity of biallelic missense variants can be challenging. Here, we use a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes. We follow three missense variants with a complete deficit of homozygosity and find that their pathogenic effect in homozygous state ranges from severe childhood disease to early embryonic lethality. One of these variants is in CPSF3, a gene not previously linked to disease. From a set of clinically sequenced Icelanders, and by sequencing archival samples targeted through the Icelandic genealogy, we find four homozygous carriers. Additionally, we find two homozygous carriers of Mexican descent of another missense variant in CPSF3. All six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone. Here, we show how the absence of certain homozygous genotypes from a large population set can elucidate causes of previously unexplained recessive diseases and early miscarriage.Sacchi Foundatio

COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground: Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. Case presentation: Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein. Conclusions: This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5-BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10-21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Programme (EU-FP7/2007-2013) European Union (EU) EU-FP7-People-2011-IAPP grant Research Council of Norway KG Jebsen Stiftelsen South-East Norway Health Authorit

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Quality of life and mental health of parents of children with mental health problems.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMental health of parents and their quality of life is likely to be affected when a child in the family has a psychiatric disorder. The purpose of this study is to assess quality of life and mental health of parents of referred children waiting for service at the only child psychiatric service in Iceland, with reassessment at least 3 months after first attendance to the service. In order to do so, 208 parents of 123 children waiting for psychiatric care were sent the Icelandic Quality of Life (IQL), the General Health Questionnaire (GHQ-30) and the CAGE screen for alcoholism. For reassessment, responders in the first phase were assessed again with the IQL and GHQ-30, at least 3 months after initiation of child psychiatric interventions. A total of 120 of the 208 parents (58%) responded in the first phase of the study, 49 fathers and 71 mothers. The mean (+/- s, standard deviation) standardized IQL T-score was for the fathers 51+/- 7.5 but significantly lower for the mothers or 45 +/-11.5 (P = 0.001) compared to normal sample of same-age women (T-scores of 50 are normal). Nearly 55% of women compared with 26% of men were psychiatric cases, scoring 5 or higher on the GHQ. According to a CAGE score of 2 and above 16% of fathers and 14% of mother abused alcohol. No significant change occurred in parents GHQ-30 or IQL before and after initiation of treatment. We conclude that mothers of children with mental disorders have poor quality of life, and high prevalence of mental disorders; hence child psychiatry clinics need to ensure that mothers receive appropriate care along with the child