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

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Examining the Links Between Perceived Impact of Pregnancy, Depressive Symptoms, and Quality of Life During Adolescent Pregnancy: The Buffering Role of Social Support

The aims of the current study were to examine the indirect effect of the perceived impact of pregnancy on quality of life (QoL) through the severity of depressive symptoms among a sample of pregnant adolescents, and to explore whether adolescents’ satisfaction with support from their mothers (SM) or partners (SP) was a buffer of this effect. Demographic and pregnancy-related data were collected for 395 pregnant adolescents age 12–19 and were controlled for testing the proposed indirect effect. SM and SP were tested as moderators of the links between perceived impact of pregnancy and depressive symptoms and between depressive symptoms and QoL. A computational tool for path analysis-based moderation and mediation analysis as well as their combination was used to test indirect and interaction effects (PROCESS). A significant indirect effect of the perceived impact of pregnancy on QoL through the severity of depressive symptoms was found (0.51, CI = 0.29/0.78). There was no significant direct effect of the perceived impact of pregnancy on QoL after controlling for the severity of depressive symptoms. SM and SP buffered the indirect effect by weakening the association between a negative perception of the impact of pregnancy and higher severity of depressive symptoms. Identifying adolescents with a negative perception of the impact of pregnancy, improving the quality of their relations with their mothers and partners, and promoting satisfactory support from these figures may be extremely important to prevent and treat depressive symptoms and, in so doing, improve adolescents’ QoL during pregnancy

Preliminary evidence for a fronto-parietal dysfunction in able-bodied participants with a desire for limb amputation

BACKGROUND: Reports of able-bodied participants with the persisting desire for limb amputation raise legal and ethical questions that are partly due to insufficient empirical knowledge about the condition. Here, we searched for potential neurological mechanisms in participants with desire for limb amputation in order to help develop adequate nosological classifications, diagnosis, and treatment. METHODS: Semi-structured interviews were carried out with 20 participants who self-identified themselves as able-bodied individuals desiring amputation of a limb. RESULTS: The results suggest that amputation desire is not unspecific, but in most cases specific for a circumscribed part of the body. Most frequently affected was the leg, mostly on the left, non-dominant side. Left-sidedness and limb specificity was associated with elementary and complex somatosensory disturbances of the affected limb akin to those reported by neurological patients. The most frequent neurological co-morbidity was migraine headache. CONCLUSIONS: These results document the existence of an unusual condition in able-bodied participants characterized by a person's desire for the amputation of one or more particular limbs. Left-sidedness, limb specificity and somatosensory disturbances of the affected limb are suggestive of abnormal brain mechanisms in right fronto-parietal cortex. Based on this association we suggest that desire for limb amputation may be conceptualized as asomatognosia due to disturbed integration of multi-sensory information of the affected body parts into a coherent cerebral representation of the own body. This suggestion has to be regarded with caution as we did not perform any neurological examination